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  • 1.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Göpel, Sven O.
    AstraZeneca R&D Gothenburg, Dept CVMD Biosci, Gothenburg, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Foss, Aksel
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Scholz, Hanne
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 1575Article in journal (Refereed)
    Abstract [en]

    One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin: insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1 alpha and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre- treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1 alpha and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.

  • 2.
    Abdalla, Hassan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Complex Materials and Devices. Linköping University, Faculty of Science & Engineering.
    van de Ruit, Kevin
    Eindhoven University of Technology, Netherlands.
    Kemerink, Martijn
    Linköping University, Department of Physics, Chemistry and Biology, Complex Materials and Devices. Linköping University, Faculty of Science & Engineering. Eindhoven University of Technology, Netherlands.
    Effective Temperature and Universal Conductivity Scaling in Organic Semiconductors2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 16870Article in journal (Refereed)
    Abstract [en]

    We investigate the scalability of the temperature-and electric field-dependence of the conductivity of disordered organic semiconductors to universal curves by two different but commonly employed methods; by so-called universal scaling and by using the effective temperature concept. Experimentally both scaling methods were found to be equally applicable to the out-of-plane charge transport in PEDOT: PSS thin films of various compositions. Both methods are shown to be equivalent in terms of functional dependence and to have identical limiting behavior. The experimentally observed scaling behavior can be reproduced by a numerical nearest-neighbor hopping model, accounting for the Coulomb interaction, the high charge carrier concentration and the energetic disorder. The underlying physics can be captured in a simple empirical model, describing the effective temperature of the charge carrier distribution as the outcome of a heat balance between Joule heating and (effective) temperature-dependent energy loss to the lattice.

  • 3.
    Abdollahi Sani, Negar
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Wang, Xin
    Acreo Swedish ICT AB, Sweden.
    Granberg, Hjalmar
    INNVENTIA AB, Sweden.
    Andersson Ersman, Peter
    Acreo Swedish ICT AB, Sweden.
    Crispin, Xavier
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Dyreklev, Peter
    Acreo Swedish ICT AB, Sweden.
    Engquist, Isak
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Gustafsson, Göran
    Acreo Swedish ICT AB, Sweden.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self-Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano-Fibrillated Cellulose2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28921Article in journal (Refereed)
    Abstract [en]

    Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-mu Ps) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-mu Ps and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-mu Ps. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm(2), a current rectification ratio up to 4 x 10(3) between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.

  • 4.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Rzepecka, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 42733Article in journal (Refereed)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

  • 5.
    Abramavicius, V.
    et al.
    Vilnius University, Lithuania; Centre Phys Science and Technology, Lithuania.
    Pranculis, V.
    Centre Phys Science and Technology, Lithuania.
    Melianas, Armantas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Gulbinas, V.
    Centre Phys Science and Technology, Lithuania.
    Abramavicius, D.
    Vilnius University, Lithuania.
    Role of coherence and delocalization in photo-induced electron transfer at organic interfaces2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 32914Article in journal (Refereed)
    Abstract [en]

    Photo-induced charge transfer at molecular heterojunctions has gained particular interest due to the development of organic solar cells (OSC) based on blends of electron donating and accepting materials. While charge transfer between donor and acceptor molecules can be described by Marcus theory, additional carrier delocalization and coherent propagation might play the dominant role. Here, we describe ultrafast charge separation at the interface of a conjugated polymer and an aggregate of the fullerene derivative PCBM using the stochastic Schrodinger equation (SSE) and reveal the complex time evolution of electron transfer, mediated by electronic coherence and delocalization. By fitting the model to ultrafast charge separation experiments, we estimate the extent of electron delocalization and establish the transition from coherent electron propagation to incoherent hopping. Our results indicate that even a relatively weak coupling between PCBM molecules is sufficient to facilitate electron delocalization and efficient charge separation at organic interfaces.

  • 6.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 7.
    Aguilar-Calvo, Patricia
    et al.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Xiao, Xiangzhu
    Case Western Reserve University, OH 44116 USA.
    Bett, Cyrus
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; US FDA, MD USA.
    Erana, Hasier
    CIC bioGUNE, Spain.
    Soldau, Katrin
    University of Calif San Diego, CA 92093 USA.
    Castilla, Joaquin
    University of Calif San Diego, CA 92093 USA; CIC bioGUNE, Spain; Ikerbasque, Spain.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Surewicz, Witold K.
    Case Western Reserve University, OH 44116 USA.
    Sigurdson, Christina J.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; University of Calif Davis, CA 95616 USA.
    Post-translational modifications in PrP expand the conformational diversity of prions in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 43295Article in journal (Refereed)
    Abstract [en]

    Misfolded prion protein aggregates (PrPSc) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-beta, tau, alpha-synuclein, and serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)anchorless prion protein, PrPC, together with hydrogen-deuterium exchange coupled with mass spectrometry (HXMS) and a battery of biochemical and biophysical tools to investigate how posttranslational modifications impact the aggregated prion protein properties and disease phenotype. Four GPI-anchorless prion strains caused a nearly identical clinical and pathological disease phenotype, yet maintained their structural diversity in the anchorless state. HXMS studies revealed that GPIanchorless PrPSc is characterized by substantially higher protection against hydrogen/deuterium exchange in the C-terminal region near the N-glycan sites, suggesting this region had become more ordered in the anchorless state. For one strain, passage of GPI-anchorless prions into wild type mice led to the emergence of a novel strain with a unique biochemical and phenotypic signature. For the new strain, histidine hydrogen-deuterium mass spectrometry revealed altered packing arrangements of beta-sheets that encompass residues 139 and 186 of PrPSc. These findings show how variation in posttranslational modifications may explain the emergence of new protein conformations in vivo and also provide a basis for understanding how the misfolded protein structure impacts the disease.

  • 8.
    Aho, Vilma
    et al.
    Department of Physiology, Faculty of Medicine, University of Helsinki, Finland.
    Ollila, Hanna M
    Department of Physiology, Faculty of Medicine, University of Helsinki, Finland; Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, University of Helsinki, Helsinki University Hospital, Finland; Stanford University Center for Sleep Sciences, Palo Alto, CA, United States.
    Kronholm, Erkki
    Department of Chronic Disease Prevention, Population Studies Unit, National Institute for Health and Welfare, Turku, Finland.
    Bondia-Pons, Isabel
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Soininen, Pasi
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
    Kangas, Antti J
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppälä, Ilkka
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Kettunen, Johannes
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
    Oikonen, Mervi
    Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
    Raitoharju, Emma
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Hyötyläinen, Tuulia
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Kähönen, Mika
    Department of Clinical Physiology, University of Tampere, Tampere University Hospital, Tampere, Finland.
    Viikari, Jorma S A
    Department of Medicine, University of Turku, Division of Medicine, Turku University Hospital, Turku, Finland.
    Härmä, Mikko
    Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland.
    Sallinen, Mikael
    Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland; Agora Center, University of Jyväskylä, Jyväskylä, Finland.
    Olkkonen, Vesa M
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Institute of Biomedicine, Anatomy, University of Helsinki, Finland.
    Alenius, Harri
    Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
    Jauhiainen, Matti
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.
    Paunio, Tiina
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, University of Helsinki, Helsinki University Hospital, Finland.
    Lehtimäki, Terho
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Salomaa, Veikko
    Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
    Orešič, Matej
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Raitakari, Olli T
    Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
    Ala-Korpela, Mika
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Oulu University Hospital, Oulu, Finland; Computational Medicine, School of Social and Community Medicine, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
    Porkka-Heiskanen, Tarja
    Department of Physiology, Faculty of Medicine, University of Helsinki, Finland.
    Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 24828Article in journal (Refereed)
    Abstract [en]

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

  • 9.
    Ahrens, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Amselem, Elias
    Stockholm University, Faculty of Science, Department of Physics.
    Cabello, Adan
    Stockholm University, Faculty of Science, Department of Physics. University of Sevilla, Spain.
    Bourennane, Mohamed
    Stockholm University, Faculty of Science, Department of Physics.
    Two Fundamental Experimental Tests of Nonclassicality with Qutrits2013In: Scientific Reports, ISSN 2045-2322, Vol. 3, 2170Article in journal (Refereed)
    Abstract [en]

    We report two fundamental experiments on three-level quantum systems (qutrits). The first one tests the simplest task for which quantum mechanics provides an advantage with respect to classical physics. The quantum advantage is certified by the violation of Wright's inequality, the simplest classical inequality violated by quantum mechanics. In the second experiment, we obtain contextual correlations by sequentially measuring pairs of compatible observables on a qutrit, and show the violation of Klyachko et al.'s inequality, the most fundamental noncontextuality inequality violated by qutrits. Our experiment tests exactly Klyachko et al.'s inequality, uses the same measurement procedure for each observable in every context, and implements the sequential measurements in any possible order.

  • 10.
    Akhtar, Farid
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Material Science.
    Ogunwumi, Steven
    Crystalline Materials Research, Corning Incorporated, Corning, New York, USA..
    Bergström, Lennart
    Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden.
    Thin zeolite laminates for rapid and energy-efficient carbon capture2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 10988Article in journal (Refereed)
    Abstract [en]

    Thin, binder-less zeolite NaX laminates, with thicknesses ranging between 310 to 750 μm and widths exceeding 50 mm and biaxial tensile strength in excess of 3 MPa, were produced by pulsed current processing. The NaX laminates displayed a high CO2 adsorption capacity and high binary CO2-over-N2 and CO2-over-CH4 selectivity, suitable for CO2 capture from flue gas and upgrading of raw biogas. The thin laminates displayed a rapid CO2 uptake; NaX laminates with a thickness of 310 μm were saturated to 40% of their CO2 capacity within 24 seconds. The structured laminates of 310 μm thickness and 50 mm thickness would offer low pressure drop and efficient carbon capture performance in a laminate-based swing adsorption technology.

  • 11.
    Alatalo, Juha M
    et al.
    Qatar University.
    Jägerbrand, Annika K
    Swedish National Road and Transport Research Institute, Society, environment and transport, Environment.
    Molau, Ulf
    Göteborgs Universitet.
    Impacts of different climate change regimes and extreme climatic events on an alpine meadow community2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 21720Article in journal (Refereed)
    Abstract [en]

    Climate variability is expected to increase in future but there exist very few experimental studies that apply different warming regimes on plant communities over several years. We studied an alpine meadow community under three warming regimes over three years. Treatments consisted of (a) a constant level of warming with open-top chambers (ca. 1.9 °C above ambient), (b) yearly stepwise increases in warming (increases of ca. 1.0, 1.9 and 3.5 °C), and (c) pulse warming, a single first-year pulse event of warming (increase of ca. 3.5 °C). Pulse warming and stepwise warming was hypothesised to cause distinct first-year and third-year effects, respectively. We found support for both hypotheses; however, the responses varied among measurement levels (whole community, canopy, bottom layer, and plant functional groups), treatments, and time. Our study revealed complex responses of the alpine plant community to the different experimentally imposed climate warming regimes. Plant cover, height and biomass frequently responded distinctly to the constant level of warming, the stepwise increase in warming and the extreme pulse-warming event. Notably, we found that stepwise warming had an accumulating effect on biomass, the responses to the different warming regimes varied among functional groups, and the short-term perturbations had negative effect on species richness and diversity.

  • 12. Alatalo, Juha M
    et al.
    Jägerbrand, Annika K
    Molau, Ulf
    Impacts of different climate change regimes and extreme climatic events on an alpine meadow community2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Climate variability is expected to increase in future but there exist very few experimental studies that apply different warming regimes on plant communities over several years. We studied an alpine meadow community under three warming regimes over three years. Treatments consisted of (a) a constant level of warming with open-top chambers (ca. 1.9 °C above ambient), (b) yearly stepwise increases in warming (increases of ca. 1.0, 1.9 and 3.5 °C), and (c) pulse warming, a single first-year pulse event of warming (increase of ca. 3.5 °C). Pulse warming and stepwise warming was hypothesised to cause distinct first-year and third-year effects, respectively. We found support for both hypotheses; however, the responses varied among measurement levels (whole community, canopy, bottom layer, and plant functional groups), treatments, and time. Our study revealed complex responses of the alpine plant community to the different experimentally imposed climate warming regimes. Plant cover, height and biomass frequently responded distinctly to the constant level of warming, the stepwise increase in warming and the extreme pulse-warming event. Notably, we found that stepwise warming had an accumulating effect on biomass, the responses to the different warming regimes varied among functional groups, and the short-term perturbations had negative effect on species richness and diversity

  • 13. Alatalo, Juha M
    et al.
    Jägerbrand, Annika K
    Čuchta, Peter
    Collembola at three alpine subarctic sites resistant to twenty years of experimental warming2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5Article in journal (Refereed)
    Abstract [en]

    This study examined the effects of micro-scale, site and 19 and 21 years of experimental warming on Collembola in three contrasting alpine subarctic plant communities (poor heath, rich meadow, wet meadow). Unexpectedly, experimental long-term warming had no significant effect on species richness, effective number of species, total abundance or abundance of any Collembola species. There were micro-scale effects on species richness, total abundance, and abundance of 10 of 35 species identified. Site had significant effect on effective number of species, and abundance of six species, with abundance patterns differing between sites. Site and long-term warming gave non-significant trends in species richness. The highest species richness was observed in poor heath, but mean species richness tended to be highest in rich meadow and lowest in wet meadow. Warming showed a tendency for a negative impact on species richness. This long-term warming experiment across three contrasting sites revealed that Collembola is capable of high resistance to climate change. We demonstrated that micro-scale and site effects are the main controlling factors for Collembola abundance in high alpine subarctic environments. Thus local heterogeneity is likely important for soil fauna composition and may play a crucial role in buffering Collembola against future climate change.

  • 14.
    Alatalo, Juha M
    et al.
    Qatar University.
    Jägerbrand, Annika
    Swedish National Road and Transport Research Institute, Society, environment and transport, Environment.
    Čuchta, Peter
    Academy of Science of the Czech Republic.
    Collembola at three alpine subarctic sites resistant to twenty years of experimental warming2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 18161Article in journal (Refereed)
    Abstract [en]

    This study examined the effects of micro-scale, site and 19 and 21 years of experimental warming on Collembola in three contrasting alpine subarctic plant communities (poor heath, rich meadow, wet meadow). Unexpectedly, experimental long-term warming had no significant effect on species richness, effective number of species, total abundance or abundance of any Collembola species. There were micro-scale effects on species richness, total abundance, and abundance of 10 of 35 species identified. Site had significant effect on effective number of species, and abundance of six species, with abundance patterns differing between sites. Site and long-term warming gave non-significant trends in species richness.

    The highest species richness was observed in poor heath, but mean species richness tended to be highest in rich meadow and lowest in wet meadow. Warming showed a tendency for a negative impact on species richness. This long-term warming experiment across three contrasting sites revealed that Collembola is capable of high resistance to climate change. We demonstrated that micro-scale and site effects are the main controlling factors for Collembola abundance in high alpine subarctic environments. Thus local heterogeneity is likely important for soil fauna composition and may play a crucial role in buffering Collembola against future climate change.

  • 15.
    Alatalo, Juha M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Little, Chelsea J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Jagerbrand, Annika K.
    Molau, Ulf
    Vascular plant abundance and diversity in an alpine heath under observed and simulated global change2015In: Scientific Reports, ISSN 2045-2322, Vol. 5, 10197Article in journal (Refereed)
    Abstract [en]

    Global change is predicted to cause shifts in species distributions and biodiversity in arctic tundra. We applied factorial warming and nutrient manipulation to a nutrient and species poor alpine/arctic heath community for seven years. Vascular plant abundance in control plots increased by 31%. There were also notable changes in cover in the nutrient and combined nutrient and warming treatments, with deciduous and evergreen shrubs declining, grasses overgrowing these plots. Sedge abundance initially increased significantly with nutrient amendment and then declined, going below initial values in the combined nutrient and warming treatment. Nutrient addition resulted in a change in dominance hierarchy from deciduous shrubs to grasses. We found significant declines in vascular plant diversity and evenness in the warming treatment and a decline in diversity in the combined warming and nutrient addition treatment, while nutrient addition caused a decline in species richness. The results give some experimental support that species poor plant communities with low diversity may be more vulnerable to loss of species diversity than communities with higher initial diversity. The projected increase in nutrient deposition and warming may therefore have negative impacts on ecosystem processes, functioning and services due to loss of species diversity in an already impoverished environment.

  • 16. Alatalo, Juha M
    et al.
    Little, Chelsea J
    Jägerbrand, Annika K
    Molau, Ulf
    Vascular plant abundance and diversity in an alpine heath under observed and simulated global change2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Global change is predicted to cause shifts in species distributions and biodiversity in arctic tundra. We applied factorial warming and nutrient manipulation to a nutrient and species poor alpine/arctic heath community for seven years. Vascular plant abundance in control plots increased by 31%. There were also notable changes in cover in the nutrient and combined nutrient and warming treatments, with deciduous and evergreen shrubs declining, grasses overgrowing these plots. Sedge abundance initially increased significantly with nutrient amendment and then declined, going below initial values in the combined nutrient and warming treatment. Nutrient addition resulted in a change in dominance hierarchy from deciduous shrubs to grasses. We found significant declines in vascular plant diversity and evenness in the warming treatment and a decline in diversity in the combined warming and nutrient addition treatment, while nutrient addition caused a decline in species richness. The results give some experimental support that species poor plant communities with low diversity may be more vulnerable to loss of species diversity than communities with higher initial diversity. The projected increase in nutrient deposition and warming may therefore have negative impacts on ecosystem processes, functioning and services due to loss of species diversity in an already impoverished environment.

  • 17.
    Alatalo, Juha, M.
    et al.
    Uppsala Universitet.
    Little, Chelsea, J.
    Uppsala Universitet.
    Jägerbrand, Annika
    Swedish National Road and Transport Research Institute, Society, environment and transport, Environment.
    Molau, Ulf
    Göteborgs Universitet.
    Vascular plant abundance and diversity in an alpine heath under observed and simulated global change2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 1-11 p., 10197Article in journal (Refereed)
    Abstract [en]

    Global change is predicted to cause shifts in species distributions and biodiversity in arctic tundra. We applied factorial warming and nutrient manipulation to a nutrient and species poor alpine/arctic heath community for seven years. Vascular plant abundance in control plots increased by 31%. There were also notable changes in cover in the nutrient and combined nutrient and warming treatments, with deciduous and evergreen shrubs declining, grasses overgrowing these plots. Sedge abundance initially increased significantly with nutrient amendment and then declined, going below initial values in the combined nutrient and warming treatment. Nutrient addition resulted in a change in dominance hierarchy from deciduous shrubs to grasses. We found significant declines in vascular plant diversity and evenness in the warming treatment and a decline in diversity in the combined warming and nutrient addition treatment, while nutrient addition caused a decline in species richness. The results give some experimental support that species poor plant communities with low diversity may be more vulnerable to loss of species diversity than communities with higher initial diversity. The projected increase in nutrient deposition and warming may therefore have negative impacts on ecosystem processes, functioning and services due to loss of species diversity in an already impoverished environment.

  • 18.
    Alene Asres, Georgies
    et al.
    University of Oulu, Finland.
    Dombovari, Aron
    University of Oulu, Finland.
    Sipola, Teemu
    University of Oulu, Finland.
    Puskas, Robert
    University of Szeged, Hungary.
    Kukovecz, Akos
    University of Szeged, Hungary; MTA SZTE Lendulet Porous Nanocomposites Research Grp, Hungary.
    Konya, Zoltan
    University of Szeged, Hungary; MTA SZTE React Kinet and Surface Chemistry Research Grp, Hungary.
    Popov, Alexey
    University of Oulu, Finland.
    Lin, Jhih-Fong
    University of Oulu, Finland.
    Lorite, Gabriela S.
    University of Oulu, Finland.
    Mohl, Melinda
    University of Oulu, Finland.
    Toth, Geza
    University of Oulu, Finland.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, Faculty of Science & Engineering. University of Oulu, Finland.
    Kordas, Krisztian
    University of Oulu, Finland.
    A novel WS2 nanowire-nanoflake hybrid material synthesized from WO3 nanowires in sulfur vapor2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 25610Article in journal (Refereed)
    Abstract [en]

    In this work, WS2 nanowire-nanoflake hybrids are synthesized by the sulfurization of hydrothermally grown WO3 nanowires. The influence of temperature on the formation of products is optimized to grow WS2 nanowires covered with nanoflakes. Current-voltage and resistance-temperature measurements carried out on random networks of the nanostructures show nonlinear characteristics and negative temperature coefficient of resistance indicating that the hybrids are of semiconducting nature. Bottom gated field effect transistor structures based on random networks of the hybrids show only minor modulation of the channel conductance upon applied gate voltage, which indicates poor electrical transport between the nanowires in the random films. On the other hand, the photo response of channel current holds promise for cost-efficient solution process fabrication of photodetector devices working in the visible spectral range.

  • 19.
    Alexander-Webber, J. A.
    et al.
    University of Oxford, England; University of Cambridge, England.
    Huang, J.
    University of Oxford, England.
    Maude, D. K.
    CNRS UGA UPS INSA, France.
    Janssen, T. J. B. M.
    National Phys Lab, England.
    Tzalenchuk, A.
    National Phys Lab, England; Royal Holloway University of London, England.
    Antonov, V.
    Royal Holloway University of London, England.
    Yager, T.
    Chalmers, Sweden.
    Lara-Avila, S.
    Chalmers, Sweden.
    Kubatkin, S.
    Chalmers, Sweden.
    Yakimova, Rositsa
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Nicholas, R. J.
    University of Oxford, England.
    Giant quantum Hall plateaus generated by charge transfer in epitaxial graphene2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 30296Article in journal (Refereed)
    Abstract [en]

    Epitaxial graphene has proven itself to be the best candidate for quantum electrical resistance standards due to its wide quantum Hall plateaus with exceptionally high breakdown currents. However one key underlying mechanism, a magnetic field dependent charge transfer process, is yet to be fully understood. Here we report measurements of the quantum Hall effect in epitaxial graphene showing the widest quantum Hall plateau observed to date extending over 50 T, attributed to an almost linear increase in carrier density with magnetic field. This behaviour is strong evidence for field dependent charge transfer from charge reservoirs with exceptionally high densities of states in close proximity to the graphene. Using a realistic framework of broadened Landau levels we model the densities of donor states and predict the field dependence of charge transfer in excellent agreement with experimental results, thus providing a guide towards engineering epitaxial graphene for applications such as quantum metrology.

  • 20. Al-Henhena, Nawal
    et al.
    Khalifa, Shaden A. M.
    Ying, Rozaida Poh Yuen
    Hassandarvish, Pouya
    Rouhollahi, Elham
    Al-Wajeeh, Nahla Saeed
    Ali, Habibah Mohd
    Abdulla, Mahmood Ameen
    El-Seedi, Hesham R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
    Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon2015In: Scientific Reports, ISSN 2045-2322, Vol. 5, 13312Article in journal (Refereed)
    Abstract [en]

    In this work, microscopic and histological studies suggest that Strobilanthes crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. S. crispus is considered a traditional medicine and used as an antioxidant. Its leaf contains a large amount of phenolic compounds to which its radical scavenging role is attributed and enhance its ability to eradicate oxidative stress reactions. The study was designed to determine the chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by elucidating the effect of the extract on intermediate biomarkers which can be used as effective predictors of colon cancer. S. crispus was analyzed for DPPH free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results indicated that S. crispus oral administration significantly inhibited colorectal carcinogenesis induced by AOM as revealed by the reduction in the number of ACF. S. crispus down-regulated the expression of PCNA, Bcl2 and beta-catenin. Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and stimulatory effect on CAT and GPx activities. These results demonstrate that S. crispus is a chemopreventive agent for colorectal cancer through the suppression of early and intermediate carcinogenic phases that may be related to its flavonoid content.

  • 21.
    Alizadeh, Javad
    et al.
    University of Manitoba, Canada.
    Zeki, Amir A.
    Centre Comparat Resp Biol and Med, CA USA.
    Mirzaei, Nima
    University of Manitoba, Canada.
    Tewary, Sandipan
    University of Manitoba, Canada.
    Rezaei Moghadam, Adel
    University of Manitoba, Canada; University of Manitoba, Canada.
    Glogowska, Aleksandra
    University of Manitoba, Canada.
    Nagakannan, Pandian
    University of Manitoba, Canada.
    Eftekharpour, Eftekhar
    University of Manitoba, Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Gordon, Joseph W.
    University of Manitoba, Canada; University of Manitoba, Canada; University of Manitoba, Canada.
    Xu, Fred. Y.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Field, Jared T.
    University of Manitoba, Canada.
    Yoneda, Ken Y.
    Centre Comparat Resp Biol and Med, CA USA.
    Kenyon, Nicholas J.
    Centre Comparat Resp Biol and Med, CA USA.
    Hashemi, Mohammad
    Zehedan University of Medical Science, Iran.
    Hatch, Grant M.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Hombach-Klonisch, Sabine
    University of Manitoba, Canada.
    Klonisch, Thomas
    University of Manitoba, Canada.
    Ghavami, Saeid
    University of Manitoba, Canada; University of Manitoba, Canada; Shiraz University of Medical Science, Iran.
    Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 44841Article in journal (Refereed)
    Abstract [en]

    The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP-and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB231( breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

  • 22. Allas, Ular
    et al.
    Toom, Lauri
    Selyutina, Anastasia
    Maeorg, Uno
    Medina, Ricardo
    Merits, Andres
    Rinken, Ago
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, Tartu 50411, Estonia.
    Kaldalu, Niilo
    Tenson, Tanel
    Antibacterial activity of the nitrovinylfuran G1 (Furvina) and its conversion products2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 36844Article in journal (Refereed)
    Abstract [en]

    2-Bromo-5-(2-bromo-2-nitrovinyl) furan (G1 or Furvina) is an antimicrobial with a direct reactivity against thiol groups. It is active against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. By reacting with thiol groups it causes direct damage to proteins but, as a result, is very short-living and interconverts into an array of reaction products. Our aim was to characterize thiol reactivity of G1 and its conversion products and establish how much of antimicrobial and cytotoxic effects are due to the primary activity of G1 and how much can be attributed to its reaction products. Stability of G1 in growth media as well as its conversion in the presence of thiols was characterized. The structures of G1 decomposition products were determined using NMR and mass-spectroscopy. Concentration-and time-dependent killing curves showed that G1 is bacteriostatic for Escherichia coli at the concentration of 16 mu g/ml and bactericidal at 32 mu g/ml. However, G1 is inefficient against non-growing E. coli. Addition of cysteine to medium reduces the antimicrobial potency of G1. Nevertheless, the reaction products of G1 and cysteine enabled prolonged antimicrobial action of the drug. Therefore, the activity of 2-bromo-5-(2-bromo-2-nitrovinyl) furan is a sum of its immediate reactivity and the antibacterial effects of the conversion products.

  • 23.
    Alling, Björn
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Armiento, Rickard
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Rosén, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Hultman, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    A theoretical investigation of mixing thermodynamics, age-hardening potential, and electronic structure of ternary (M1-xMxB2)-M-1-B-2 alloys with AlB2 type structure2015In: Scientific Reports, ISSN 2045-2322, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Transition metal diborides are ceramic materials with potential applications as hard protective thin films and electrical contact materials. We investigate the possibility to obtain age hardening through isostructural clustering, including spinodal decomposition, or ordering-induced precipitation in ternary diboride alloys. By means of first-principles mixing thermodynamics calculations, 45 ternary (M1-xMxB2)-M-1-B-2 alloys comprising (MB2)-B-i (M-i = Mg, Al, Sc, Y, Ti, Zr, Hf, V, Nb, Ta) with AlB2 type structure are studied. In particular Al1-xTixB2 is found to be of interest for coherent isostructural decomposition with a strong driving force for phase separation, while having almost concentration independent a and c lattice parameters. The results are explained by revealing the nature of the electronic structure in these alloys, and in particular, the origin of the pseudogap at E-F in TiB2, ZrB2, and HfB2.

  • 24.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA.;King Abdulaziz Univ, Dept Phys, Rabigh 21911, Saudi Arabia..
    Andersson, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    DNA intercalation optimized by two-step molecular lock mechanism2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 37993Article in journal (Refereed)
    Abstract [en]

    The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.

  • 25. Almlöf, Jonas Carlsson
    et al.
    Alexsson, Andrei
    Imgenberg-Kreuz, Juliana
    Sylwan, Lina
    Backlin, Christofer
    Leonard, Dag
    Nordmark, Gunnel
    Tandre, Karolina
    Eloranta, Maija-Leena
    Padyukov, Leonid
    Bengtsson, Christine
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Jonsen, Andreas
    Dahlqvist, Solbritt Rantapaa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Sjowall, Christopher
    Bengtsson, Anders A.
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Ronnblom, Lars
    Sandling, Johanna K.
    Syvanen, Ann-Christine
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 6236Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

  • 26. Altfeder, Igor
    et al.
    Voevodin, Andrey A.
    Check, Michael H.
    Eichfeld, Sarah M.
    Robinson, Joshua A.
    Balatsky, Alexander V.
    Stockholm University, Nordic Institute for Theoretical Physics (Nordita). Los Alamos National Laboratory, USA.
    Scanning Tunneling Microscopy Observation of Phonon Condensate2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 43214Article in journal (Refereed)
    Abstract [en]

    Using quantum tunneling of electrons into vibrating surface atoms, phonon oscillations can be observed on the atomic scale. Phonon interference patterns with unusually large signal amplitudes have been revealed by scanning tunneling microscopy in intercalated van der Waals heterostructures. Our results show that the effective radius of these phonon quasi-bound states, the real-space distribution of phonon standing wave amplitudes, the scattering phase shifts, and the nonlinear intermode coupling strongly depend on the presence of defect-induced scattering resonance. The observed coherence of these quasi-bound states most likely arises from phase-and frequency-synchronized dynamics of all phonon modes, and indicates the formation of many-body condensate of optical phonons around resonant defects. We found that increasing the strength of the scattering resonance causes the increase of the condensate droplet radius without affecting the condensate fraction inside it. The condensate can be observed at room temperature.

  • 27. Altfeder, Igor
    et al.
    Voevodin, Andrey A.
    Check, Michael H.
    Eichfeld, Sarah M.
    Robinson, Joshua A.
    Balatsky, Alexander V.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Scanning Tunneling Microscopy Observation of Phonon Condensate2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 43214Article in journal (Refereed)
    Abstract [en]

    Using quantum tunneling of electrons into vibrating surface atoms, phonon oscillations can be observed on the atomic scale. Phonon interference patterns with unusually large signal amplitudes have been revealed by scanning tunneling microscopy in intercalated van der Waals heterostructures. Our results show that the effective radius of these phonon quasi-bound states, the real-space distribution of phonon standing wave amplitudes, the scattering phase shifts, and the nonlinear intermode coupling strongly depend on the presence of defect-induced scattering resonance. The observed coherence of these quasi-bound states most likely arises from phase-and frequency-synchronized dynamics of all phonon modes, and indicates the formation of many-body condensate of optical phonons around resonant defects. We found that increasing the strength of the scattering resonance causes the increase of the condensate droplet radius without affecting the condensate fraction inside it. The condensate can be observed at room temperature.

  • 28.
    Ameur, Adam
    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.
    Meiring, Tracy L.
    Bunikis, Ignas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Häggqvist, Susana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindau, Cecilia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lindberg, Julia Hedlund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustavsson, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mbulawa, Zizipho Z. A.
    Williamson, Anna-Lise
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing2014In: Scientific Reports, ISSN 2045-2322, Vol. 4, 4398- p.Article in journal (Refereed)
    Abstract [en]

    Infections by HIV increase the risk of acquiring secondary viral and bacterial infections and methods are needed to determine the spectrum of co-infections for proper treatment. We used rolling circle amplification (RCA) and Ion Proton sequencing to investigate the vaginal microbiome of 20 HIV positive women from South Africa. A total of 46 different human papillomavirus (HPV) types were found, many of which are not detected by existing genotyping assays. Moreover, the complete genomes of two novel HPV types were determined. Abundance of HPV infections was highly correlated with real-time PCR estimates, indicating that the RCA-Proton method can be used for quantification of individual pathogens. We also identified a large number of other viral, bacterial and parasitic co-infections and the spectrum of these co-infections varied widely between individuals. Our method provides rapid detection of a broad range of pathogens and the ability to reconstruct complete genomes of novel infectious agents.

  • 29.
    Amselem, Elias
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Sadiq, Muhamad
    Stockholm University, Faculty of Science, Department of Physics.
    Bourennane, Mohamed
    Stockholm University, Faculty of Science, Department of Physics.
    Experimental bound entanglement through a Pauli channel2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, 1966Article in journal (Refereed)
    Abstract [en]

    Understanding the characteristics of a quantum systems when affected by noise is one of the biggest challenges for quantum technologies. The general Pauli error channel is an important lossless channel for quantum communication. In this work we consider the effects of a Pauli channel on a pure four-qubit state and simulate the Pauli channel experimentally by studying the action on polarization encoded entangled photons. When the noise channel acting on the photons is correlated, a set spanned by four orthogonal bound entangled states can be generated. We study this interesting case experimentally and demonstrate that products of Bell states can be brought into a bound entangled regime. We find states in the set of bound entangled states which experimentally violate the CHSH inequality while still possessing a positive partial transpose.

  • 30. Anderson, Bruce T.
    et al.
    Hassanzadeh, Pedram
    Caballero, Rodrigo
    Stockholm University, Faculty of Science, Department of Meteorology .
    Persistent anomalies of the extratropical Northern Hemisphere wintertime circulation as an initiator of El Nino/Southern Oscillation events2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 10145Article in journal (Refereed)
    Abstract [en]

    Climates across both hemispheres are strongly influenced by tropical Pacific variability associated with the El Nino/Southern Oscillation (ENSO). Conversely, extratropical variability also can affect the tropics. In particular, seasonal-mean alterations of near-surface winds associated with the North Pacific Oscillation (NPO) serve as a significant extratropical forcing agent of ENSO. However, it is still unclear what dynamical processes give rise to year-to-year shifts in these long-lived NPO anomalies. Here we show that intraseasonal variability in boreal winter pressure patterns over the Central North Pacific (CNP) imparts a significant signature upon the seasonal-mean circulations characteristic of the NPO. Further we show that the seasonal-mean signature results in part from year-to-year variations in persistent, quasi-stationary low-pressure intrusions into the subtropics of the CNP, accompanied by the establishment of persistent, quasi-stationary high-pressure anomalies over high latitudes of the CNP. Overall, we find that the frequency of these persistent extratropical anomalies (PEAs) during a given winter serves as a key modulator of intraseasonal variability in extratropical North Pacific circulations and, through their influence on the seasonal-mean circulations in and around the southern lobe of the NPO, the state of the equatorial Pacific 9-12 months later.

  • 31.
    Andersson, Anna-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Blanka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lorell, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed)
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

  • 32.
    Andersson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Almqvist, Bjarne S. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Burchardt, Steffi
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Troll, Valentin R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Malehmir, Alireza
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Snowball, Ian
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Natural Resources and Sustainable Development.
    Kubler, Lutz
    Geol Survey Sweden, Uppsala, Sweden..
    Magma transport in sheet intrusions of the Alnö carbonatite complex, central Sweden2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 27635Article in journal (Refereed)
    Abstract [en]

    Magma transport through the Earth's crust occurs dominantly via sheet intrusions, such as dykes and cone-sheets, and is fundamental to crustal evolution, volcanic eruptions and geochemical element cycling. However, reliable methods to reconstruct flow direction in solidified sheet intrusions have proved elusive. Anisotropy of magnetic susceptibility (AMS) in magmatic sheets is often interpreted as primary magma flow, but magnetic fabrics can be modified by post-emplacement processes, making interpretation of AMS data ambiguous. Here we present AMS data from cone-sheets in the Alno carbonatite complex, central Sweden. We discuss six scenarios of syn- and post-emplacement processes that can modify AMS fabrics and offer a conceptual framework for systematic interpretation of magma movements in sheet intrusions. The AMS fabrics in the Alno cone-sheets are dominantly oblate with magnetic foliations parallel to sheet orientations. These fabrics may result from primary lateral flow or from sheet closure at the terminal stage of magma transport. As the cone-sheets are discontinuous along their strike direction, sheet closure is the most probable process to explain the observed AMS fabrics. We argue that these fabrics may be common to cone-sheets and an integrated geology, petrology and AMS approach can be used to distinguish them from primary flow fabrics.

  • 33.
    Andersson, Magnus
    et al.
    Department of Earth Sciences, Uppsala University.
    Malehmir, Alireza
    Department of Earth Sciences, Uppsala University.
    Troll, Valentin R.
    Department of Earth Sciences, Uppsala University.
    Dehghannejad, Mahdieh
    Department of Earth Sciences, Uppsala University.
    Juhlin, Christopher
    Department of Earth Sciences, Uppsala University.
    Ask, Maria
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Geosciences and Environmental Engineering.
    Carbonatite ring-complexes explained by caldera-style volcanism2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, 1677Article in journal (Refereed)
    Abstract [en]

    Carbonatites are rare, carbonate-rich magmatic rocks that make up a minute portion of the crust only, yet they are of great relevance for our understanding of crustal and mantle processes. Although they occur in all continents and from Archaean to present, the deeper plumbing system of carbonatite ring-complexes is usually poorly constrained. Here, we show that carbonatite ring-complexes can be explained by caldera-style volcanism. Our geophysical investigation of the Alnö carbonatite ring-complex in central Sweden identifies a solidified saucer-shaped magma chamber at ∼3 km depth that links to surface exposures through a ring fault system. Caldera subsidence during final stages of activity caused carbonatite eruptions north of the main complex, providing the crucial element to connect plutonic and eruptive features of carbonatite magmatism. The way carbonatite magmas are stored, transported and erupt at the surface is thus comparable to known emplacement styles from silicic calderas.

  • 34.
    Andersson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Malehmir, Alireza
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Troll, Valentin R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Dehghannejad, Mahdieh
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Juhlin, Christopher
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Ask, Maria
    Carbonatite ring-complexes explained by caldera-style volcanism2013In: Scientific Reports, ISSN 2045-2322, Vol. 3, 1677- p.Article in journal (Refereed)
    Abstract [en]

    Carbonatites are rare, carbonate-rich magmatic rocks that make up a minute portion of the crust only, yet they are of great relevance for our understanding of crustal and mantle processes. Although they occur in all continents and from Archaean to present, the deeper plumbing system of carbonatite ring-complexes is usually poorly constrained. Here, we show that carbonatite ring-complexes can be explained by caldera-style volcanism. Our geophysical investigation of the Alno carbonatite ring-complex in central Sweden identifies a solidified saucer-shaped magma chamber at similar to 3 km depth that links to surface exposures through a ring fault system. Caldera subsidence during final stages of activity caused carbonatite eruptions north of the main complex, providing the crucial element to connect plutonic and eruptive features of carbonatite magmatism. The way carbonatite magmas are stored, transported and erupt at the surface is thus comparable to known emplacement styles from silicic calderas.

  • 35.
    Andersson, Mikael S.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Pappas, Spyridon D.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Stopfel, Henry
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Östman, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Stein, A.
    Brookhaven Natl Lab, Ctr Funct Nanomat, POB 5000, Upton, NY 11973 USA..
    Nordblad, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Mathieu, Roland
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Hjörvarsson, Björgvin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Kapaklis, Vassilios
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Thermally induced magnetic relaxation in square artificial spin ice2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 37097Article in journal (Refereed)
    Abstract [en]

    The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice - we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

  • 36.
    Andersson, Richard L.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Ström, Valter
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering, Engineering Material Physics.
    Gedde, Ulf W.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Mallon, Peter E.
    Hedenqvist, Mikael S.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Olsson, Richard T.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Micromechanics of ultra-toughened electrospun PMMA/PEO fibres as revealed by in-situ tensile testing in an electron microscope2014In: Scientific Reports, ISSN 2045-2322, Vol. 4, 6335- p.Article in journal (Refereed)
    Abstract [en]

    A missing cornerstone in the development of tough micro/nano fibre systems is an understanding of the fibre failure mechanisms, which stems from the limitation in observing the fracture of objects with dimensions one hundredth of the width of a hair strand. Tensile testing in the electron microscope is herein adopted to reveal the fracture behaviour of a novel type of toughened electrospun poly(methyl methacrylate)/poly(ethylene oxide) fibre mats for biomedical applications. These fibres showed a toughness more than two orders of magnitude greater than that of pristine PMMA fibres. The in-situ microscopy revealed that the toughness were not only dependent on the initial molecular alignment after spinning, but also on the polymer formulation that could promote further molecular orientation during the formation of micro/nano-necking. The true fibre strength was greater than 150 MPa, which was considerably higher than that of the unmodified PMMA (17 MPa). This necking phenomenon was prohibited by high aspect ratio cellulose nanocrystal fillers in the ultra-tough fibres, leading to a decrease in toughness by more than one order of magnitude. The reported necking mechanism may have broad implications also within more traditional melt-spinning research.

  • 37.
    Andresen, Liis
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 36549Article in journal (Refereed)
    Abstract [en]

    The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p) ppGpp (de la Fuente-Nunez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p) ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p) ppGpp synthesis moderately sensitizes-rather than protects-E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p) ppGpp.

  • 38.
    Andresen, Liis
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Varik, Vallo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Tozawa, Yuzuru
    Jimmy, Steffi
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindberg, Stina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 35824Article in journal (Refereed)
    Abstract [en]

    The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy) alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors-a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

  • 39. Andriukonis, Eivydas
    et al.
    Gorokhova, Elena
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Kinetic N-15-isotope effects on algal growth2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 44181Article in journal (Refereed)
    Abstract [en]

    Stable isotope labeling is a standard technique for tracing material transfer in molecular, ecological and biogeochemical studies. The main assumption in this approach is that the enrichment with a heavy isotope has no effect on the organism metabolism and growth, which is not consistent with current theoretical and empirical knowledge on kinetic isotope effects. Here, we demonstrate profound changes in growth dynamics of the green alga Raphidocelis subcapitata grown in N-15-enriched media. With increasing N-15 concentration (0.37 to 50 at%), the lag phase increased, whereas maximal growth rate and total yield decreased; moreover, there was a negative relationship between the growth and the lag phase across the treatments. The latter suggests that a trade-off between growth rate and the ability to adapt to the high N-15 environment may exist. Remarkably, the lag-phase response at 3.5 at% N-15 was the shortest and deviated from the overall trend, thus providing partial support to the recently proposed Isotopic Resonance hypothesis, which predicts that certain isotopic composition is particularly favorable for living organisms. These findings confirm the occurrence of KIE in isotopically enriched algae and underline the importance of considering these effects when using stable isotope labeling in field and experimental studies.

  • 40.
    Annamalai, Alagappan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics. Division of Biotechnology, Advanced Institute of Environmental and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Republic of Korea.
    Lee, Hyun Hwi
    Choi, Sun Hee
    Lee, Su Yong
    Gracia-Espino, Eduardo
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Subramanian, Arunprabaharan
    Park, Jaedeuk
    Kong, Ki-jeong
    Jang, Jum Suk
    Sn/Be Sequentially co-doped Hematite Photoanodes for Enhanced Photoelectrochemical Water Oxidation: Effect of Be2+ as co-dopant2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 23183Article in journal (Refereed)
    Abstract [en]

    For ex-situ co-doping methods, sintering at high temperatures enables rapid diffusion of Sn4+ and Be2+ dopants into hematite (alpha-Fe2O3) lattices, without altering the nanorod morphology or damaging their crystallinity. Sn/Be co-doping results in a remarkable enhancement in photocurrent (1.7 mA/cm(2)) compared to pristine alpha-Fe2O3 (0.7 mA/cm(2)), and Sn4+ mono-doped alpha-Fe2O3 photoanodes (1.0 mA/cm(2)). From first-principles calculations, we found that Sn4+ doping induced a shallow donor level below the conduction band minimum, which does not contribute to increase electrical conductivity and photocurrent because of its localized nature. Additionally, Sn4+-doping induce local micro-strain and a decreased Fe-O bond ordering. When Be2+ was co-doped with Sn4+-doped alpha-Fe2O3 photoanodes, the conduction band recovered its original state, without localized impurities peaks, also a reduction in micro-strain and increased Fe-O bond ordering is observed. Also the sequence in which the ex-situ co-doping is carried out is very crucial, as Be/Sn co-doping sequence induces many under-coordinated O atoms resulting in a higher micro-strain and lower charge separation efficiency resulting undesired electron recombination. Here, we perform a detailed systematic characterization using XRD, FESEM, XPS and comprehensive electrochemical and photoelectrochemical studies, along with sophisticated synchrotron diffraction studies and extended X-ray absorption fine structure.

  • 41.
    Aqvist, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kamerlin, Shina C. Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15817Article in journal (Refereed)
    Abstract [en]

    Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (T Delta S-double dagger) amounts to more than 7 kcal/mol at 25 degrees C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s(-1). This entropy driven mechanism likely reflects the very high selection pressure on the speed of protein synthesis, which drives the rate of each individual GTPase towards maximal turnover rate of the whole translation cycle.

  • 42. Araujo, C. Moyses
    et al.
    Nagar, Sandeep
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Ramzan, Muhammad
    Shukla, R.
    Jayakumar, O. D.
    Tyagi, A. K.
    Liu, Yi-Sheng
    Chen, Jeng-Lung
    Glans, Per-Anders
    Chang, Chinglin
    Blomqvist, Andreas
    Lizarraga, Raquel
    Holmström, Erik
    Belova, Lyubov
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering, Engineering Material Physics.
    Guo, Jinghua
    Ahuja, Rajeev
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering, Applied Material Physics.
    Rao, K. Venkat
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Disorder-induced Room Temperature Ferromagnetism in Glassy Chromites2014In: Scientific Reports, ISSN 2045-2322, Vol. 4, 4686- p.Article in journal (Refereed)
    Abstract [en]

    We report an unusual robust ferromagnetic order above room temperature upon amorphization of perovskite [YCrO3] in pulsed laser deposited thin films. This is contrary to the usual expected formation of a spin glass magnetic state in the resulting disordered structure. To understand the underlying physics of this phenomenon, we combine advanced spectroscopic techniques and first-principles calculations. We find that the observed order-disorder transformation is accompanied by an insulator-metal transition arising from a wide distribution of Cr-O-Cr bond angles and the consequent metallization through free carriers. Similar results also found in YbCrO3-films suggest that the observed phenomenon is more general and should, in principle, apply to a wider range of oxide systems. The ability to tailor ferromagnetic order above room temperature in oxide materials opens up many possibilities for novel technological applications of this counter intuitive effect.

  • 43.
    Araujo, Carlos Moyses
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Nagar, Sandeep
    Ramzan, Muhammad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Shukla, R.
    Jayakumar, O. D.
    Tyagi, A. K.
    Liu, Yi-Sheng
    Chen, Jeng-Lung
    Glans, Per-Anders
    Chang, Chinglin
    Blomqvist, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Lizárraga, Raquel
    Holmstrom, Erik
    Belova, Lyubov
    Guo, Jinghua
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Applied Materials Physics, Department of Materials and Engineering, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.
    Rao, K. V.
    Disorder-induced Room Temperature Ferromagnetism in Glassy Chromites2014In: Scientific Reports, ISSN 2045-2322, Vol. 4, 4686- p.Article in journal (Refereed)
    Abstract [en]

    We report an unusual robust ferromagnetic order above room temperature upon amorphization of perovskite [YCrO3] in pulsed laser deposited thin films. This is contrary to the usual expected formation of a spin glass magnetic state in the resulting disordered structure. To understand the underlying physics of this phenomenon, we combine advanced spectroscopic techniques and first-principles calculations. We find that the observed order-disorder transformation is accompanied by an insulator-metal transition arising from a wide distribution of Cr-O-Cr bond angles and the consequent metallization through free carriers. Similar results also found in YbCrO3-films suggest that the observed phenomenon is more general and should, in principle, apply to a wider range of oxide systems. The ability to tailor ferromagnetic order above room temperature in oxide materials opens up many possibilities for novel technological applications of this counter intuitive effect.

  • 44.
    Aronsson, Christopher
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Zhou, Feng
    Nanyang Technology University, Singapore.
    Öberg, Per
    Linköping University, Department of Electrical Engineering, Vehicular Systems. Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Su, Haibin
    Nanyang Technology University, Singapore.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 14063Article in journal (Refereed)
    Abstract [en]

    Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide-based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials.

  • 45.
    Arshamian, Artin
    et al.
    Karolinska Institute, Sweden; Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands; Stockholm University, Sweden.
    Laska, Matthias
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Gordon, Amy R.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA.
    Norberg, Matilda
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Lahger, Christian
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Porada, Danja K.
    Karolinska Institute, Sweden.
    Jelvez Serra, Nadia
    Lund University, Sweden.
    Johansson, Emilia
    Karolinska Institute, Sweden.
    Schaefer, Martin
    Karolinska Institute, Sweden.
    Amundin, Mats
    Kolmarden Wildlife Pk, Sweden.
    Melin, Harald
    Karolinska Institute, Sweden.
    Olsson, Andreas
    Karolinska Institute, Sweden.
    Olsson, Mats J.
    Karolinska Institute, Sweden.
    Stensmyr, Marcus
    Lund University, Sweden.
    Lundstrom, Johan N.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA; University of Penn, PA 19104 USA.
    A mammalian blood odor component serves as an approach-avoidance cue across phylum border - from flies to humans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 13635Article in journal (Refereed)
    Abstract [en]

    Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

  • 46.
    Arshamian, Artin
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics. Karolinska Institutet, Sweden; Radboud University, The Netherlands.
    Laska, Matthias
    Gordon, Amy R.
    Norberg, Matilda
    Lahger, Christian
    Porada, Danja K.
    Jelvez Serra, Nadia
    Johansson, Emilia
    Schaefer, Martin
    Amundin, Mats
    Melin, Harald
    Olsson, Andreas
    Olsson, Mats J.
    Stensmyr, Marcus
    Lundström, Johan N.
    A mammalian blood odor component serves as an approach-avoidance cue across phylum border - from flies to humans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 13635Article in journal (Refereed)
    Abstract [en]

    Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

  • 47. Arslanov, Temirlan R.
    et al.
    Mollaev, Akhmedbek Yu.
    Kamilov, Ibragimkhan K.
    Arslanov, Rasul K.
    Kilanski, Lukasz
    Minikaev, Roman
    Reszka, Anna
    Lopez-Moreno, Sinhue
    Romero, Aldo H.
    Ramzan, Muhammad
    Panigrahi, Puspamitra
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Ahuja, Rajeev
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering, Applied Material Physics.
    Trukhan, Vladimir M.
    Chatterji, Tapan
    Marenkin, Sergey F.
    Shoukavaya, Tatyana V.
    Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic chalcopyrites2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 7720- p.Article in journal (Refereed)
    Abstract [en]

    Room-temperature ferromagnetism in Mn-doped chalcopyrites is a desire aspect when applying those materials to spin electronics. However, dominance of high Curie-temperatures due to cluster formation or inhomogeneities limited their consideration. Here we report how an external perturbation such as applied hydrostatic pressure in CdGeP2:Mn induces a two serial magnetic transitions from ferromagnet to non-magnet state at room temperature. This effect is related to the unconventional properties of created MnP magnetic clusters within the host material. Such behavior is also discussed in connection with ab initio density functional calculations, where the structural properties of MnP indicate magnetic transitions as function of pressure as observed experimentally. Our results point out new ways to obtain controlled response of embedded magnetic clusters.

  • 48. Arslanov, Temirlan R.
    et al.
    Mollaev, Akhmedbek Yu.
    Kamilov, Ibragimkhan K.
    Arslanov, Rasul K.
    Kilanski, Lukasz
    Minikaev, Roman
    Reszka, Anna
    Lopez-Moreno, Sinhue
    Romero, Aldo H.
    Ramzan, Muhammad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Panigrahi, Puspamitra
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Trukhan, Vladimir M.
    Chatterji, Tapan
    Marenkin, Sergey F.
    Shoukavaya, Tatyana V.
    Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic chalcopyrites2015In: Scientific Reports, ISSN 2045-2322, Vol. 5, 7720- p.Article in journal (Refereed)
    Abstract [en]

    Room-temperature ferromagnetism in Mn-doped chalcopyrites is a desire aspect when applying those materials to spin electronics. However, dominance of high Curie-temperatures due to cluster formation or inhomogeneities limited their consideration. Here we report how an external perturbation such as applied hydrostatic pressure in CdGeP2:Mn induces a two serial magnetic transitions from ferromagnet to non-magnet state at room temperature. This effect is related to the unconventional properties of created MnP magnetic clusters within the host material. Such behavior is also discussed in connection with ab initio density functional calculations, where the structural properties of MnP indicate magnetic transitions as function of pressure as observed experimentally. Our results point out new ways to obtain controlled response of embedded magnetic clusters.

  • 49.
    Asghar, Naveed
    et al.
    Södertörn University, School of Natural Science, Technology & Environmental Studies, Huddinge, Sweden .
    Lee, Yi-Ping
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Nilsson, Emma
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Lindqvist, Richard
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Kröger, Andrea
    Helmholtz Centre for Infection Research, Innate Immunity and Infection, Braunschweig, Germany; University of Magdeburg, Institute for Microbiology, Magdeburg, Germany.
    Överby, Anna K.
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 39265Article in journal (Refereed)
    Abstract [en]

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

  • 50. Asghar, Naveed
    et al.
    Lee, Yi-Ping
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nilsson, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindqvist, Richard
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Melik, Wessam
    Kröger, Andrea
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Johansson, Magnus
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 39265Article in journal (Refereed)
    Abstract [en]

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

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