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  • 151.
    Gramolelli, Silvia
    et al.
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Cheng, Jianpin
    CHU Vaudois, Dept Oncol, Lausanne, Switzerland;Univ Lausanne, Lausanne, Switzerland;Ludwig Inst Canc Res, Lausanne, Switzerland.
    Martinez-Corral, Ines
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Vaha-Koskela, Markus
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Elbasani, Endrit
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Kaivanto, Elisa
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Rantanen, Ville
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland.
    Tuohinto, Krista
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Hautaniemi, Sampsa
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland.
    Bower, Mark
    Chelsea & Westminster Hosp, London, England;Imperial Coll London, London, England.
    Haglund, Caj
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland;Univ Helsinki, Dept Surg, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Univ Helsinki, Dept Pathol, Helsinki, Finland.
    Alitalo, Kari
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Mäkinen, Taija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Petrova, Tatiana V.
    CHU Vaudois, Dept Oncol, Lausanne, Switzerland;Univ Lausanne, Lausanne, Switzerland;Ludwig Inst Canc Res, Lausanne, Switzerland.
    Lehti, Kaisa
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.
    Ojala, Paivi M.
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland;Imperial Coll London, Dept Med, Div Infect Dis, Sect Virol, London, England;Fdn Finnish Canc Inst, Helsinki, Finland.
    PROX1 is a transcriptional regulator of MMP142018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9531Article in journal (Refereed)
    Abstract [en]

    The transcription factor PROX1 is essential for development and cell fate specification. Its function in cancer is context-dependent since PROX1 has been shown to play both oncogenic and tumour suppressive roles. Here, we show that PROX1 suppresses the transcription of MMP14, a metalloprotease involved in angiogenesis and cancer invasion, by binding and suppressing the activity of MMP14 promoter. Prox1 deletion in murine dermal lymphatic vessels in vivo and in human LECs increased MMP14 expression. In a hepatocellular carcinoma cell line expressing high endogenous levels of PROX1, its silencing increased both MMP14 expression and MMP14-dependent invasion in 3D. Moreover, PROX1 ectopic expression reduced the MMP14-dependent 3D invasiveness of breast cancer cells and angiogenic sprouting of blood endothelial cells in conjunction with MMP14 suppression. Our study uncovers a new transcriptional regulatory mechanism of cancer cell invasion and endothelial cell specification.

  • 152.
    Grånäs, Oscar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
    Vinichenko, Dmitry
    Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA..
    Kaxiras, Efthimios
    Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.;Harvard Univ, Dept Phys, Cambridge, MA 02138 USA..
    Establishing the limits of efficiency of perovskite solar cells from first principles modeling2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36108Article in journal (Refereed)
    Abstract [en]

    The recent surge in research on metal-halide-perovskite solar cells has led to a seven-fold increase of efficiency, from similar to 3% in early devices to over 22% in research prototypes. Oft-cited reasons for this increase are: (i) a carrier diffusion length reaching hundreds of microns; (ii) a low exciton binding energy; and (iii) a high optical absorption coefficient. These hybrid organic-inorganic materials span a large chemical space with the perovskite structure. Here, using first-principles calculations and thermodynamic modelling, we establish that, given the range of band-gaps of the metal-halide-perovskites, the theoretical maximum efficiency limit is in the range of similar to 25-27%. Our conclusions are based on the effect of level alignment between the perovskite absorber layer and carrier-transporting materials on the performance of the solar cell as a whole. Our results provide a useful framework for experimental searches toward more efficient devices.

  • 153.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Nilsson, Cecilia
    Vastmanland Cty Hosp, Ctr Clin Res, Vasteras, Sweden.
    Markholm, Ida
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Hedenfalk, Ingrid
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Blomqvist, Carl
    Univ Helsinki, Dept Oncol, Helsinki, Finland;Orebro Univ Hosp, Dept Oncol, Orebro, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ghrelin expression is associated with a favorable outcome in male breast cancer2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 13586Article in journal (Refereed)
    Abstract [en]

    Ghrelin and obestatin are two gastrointestinal peptides, derived from a common precursor. Expression of both peptides have been found in breast cancer tissue and ghrelin has been associated with breast cancer development. Ghrelin expression is associated with longer survival in women diagnosed with invasive and node negative breast cancer. The clinical implications of the peptide expression in male breast cancer are unclear. The aim of this study was to investigate the role and potential clinical value of ghrelin and obestatin in male breast cancer. A tissue microarray of invasive male breast cancer specimens from 197 patients was immunostained with antibodies versus the two peptides. The expression of the peptides was correlated to previously known prognostic factors in breast cancer and to the outcome. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was statistically significantly correlated to breast cancer-specific survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic factor for breast cancer death in male breast cancer. Patients with tumors expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those lacking ghrelin expression. Drugs targeting ghrelin are currently being investigated in clinical studies treating metabolic or nutritional disorders. Ghrelin should be further evaluated in forthcoming studies as a prognostic marker with the aim to be included in decision algorithms.

  • 154.
    Gu, Gucci Jijuan
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Friedman, Mikaela
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ren, Ping
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Torn, Carina
    Fex, Malin
    Hampe, Christiane S.
    Lernmark, Ake
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 11196Article in journal (Refereed)
    Abstract [en]

    Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.

  • 155.
    Gudmundsson, Sanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University.
    Wilbe, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gorniok, Beata Filipek
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Molin, Anna-Maja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ekvall, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Josefin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Allalou, Amin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Gylje, Hans
    Department of Paediatrics, Central Hospital, Västerås, 721 89, Sweden..
    Kalscheuer, Vera M.
    Research Group Development and Disease, Max Planck Institute for Molecular Genetics, Berlin, 141 95, Germany..
    Ledin, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Annerén, Göran
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Bondeson, Marie-Louise
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10730Article in journal (Refereed)
    Abstract [en]

    The TATA-box binding protein associated factor 1 (TAF1) protein is a key unit of the transcription factor II D complex that serves a vital function during transcription initiation. Variants of TAF1 have been associated with neurodevelopmental disorders, but TAF1's molecular functions remain elusive. In this study, we present a five-generation family affected with X-linked intellectual disability that co-segregated with a TAF1 c. 3568C>T, p.(Arg1190Cys) variant. All affected males presented with intellectual disability and dysmorphic features, while heterozygous females were asymptomatic and had completely skewed X-chromosome inactivation. We investigated the role of TAF1 and its association to neurodevelopment by creating the first complete knockout model of the TAF1 orthologue in zebrafish. A crucial function of human TAF1 during embryogenesis can be inferred from the model, demonstrating that intact taf1 is essential for embryonic development. Transcriptome analysis of taf1 zebrafish knockout revealed enrichment for genes associated with neurodevelopmental processes. In conclusion, we propose that functional TAF1 is essential for embryonic development and specifically neurodevelopmental processes.

  • 156.
    Gustafsson, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Loryan, Irena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5308Article in journal (Refereed)
    Abstract [en]

    For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (fu,brain) is commonly used to compensate total drug concentrations for nonspecific brain tissue binding (BTB). As, homogenous BTB is assumed between species and in health and disease, rat BTB is routinely used. The impact of Alzheimer’s disease (AD) on drug BTB in brain regions of interest (ROI), i.e., fu,brain,ROI, is yet unclear. This study for the first time provides insight into regional drug BTB and the validity of employing rat fu,brain,ROI as a surrogate of human BTB, by investigating five marketed drugs in post-mortem tissue from AD patients (n = 6) and age-matched controls (n = 6). Heterogeneous drug BTB was observed in all within group comparisons independent of disease and species. The findings oppose the assumption of uniform BTB, highlighting the need of case-by-case evaluation of fu,brain,ROI in translational CNS research.

  • 157.
    Halvorsen, Cecilia Pegelow
    et al.
    Karolinska Inst, Dept Clin Res & Educ, Sodersjukhuset, Stockholm, Sweden;Sachs Children & Youth Hosp, Neonatal Unit, Stockholm, Sweden.
    Olson, Linus
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;TRAC Sweden Vietnam, Hanoi, Vietnam.
    Araujo, Ana Catarina
    Calmark Sweden AB, Stockholm, Sweden.
    Karlsson, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Calmark Sweden AB, Stockholm, Sweden.
    Nguyen, Trang Thi
    Khu, Dung T. K.
    TRAC Sweden Vietnam, Hanoi, Vietnam;Vietnam Natl Childrens Hosp, Neonatal Intens Care Unit, Hanoi, Vietnam.
    Le, Ha T. T.
    Vietnam Natl Childrens Hosp, Neonatal Intens Care Unit, Hanoi, Vietnam;Res Inst Child Hlth, Hanoi, Vietnam.
    Nguyen, Hoa T. B.
    Vietnam Natl Childrens Hosp, Neonatal Intens Care Unit, Hanoi, Vietnam;Res Inst Child Hlth, Hanoi, Vietnam.
    Winbladh, Birger
    Karolinska Inst, Dept Clin Res & Educ, Sodersjukhuset, Stockholm, Sweden.
    Russom, Aman
    KTH Royal Inst Technol, Div Nanobiotechnol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth,Sci Life Lab, Stockholm, Sweden.
    A rapid smartphone-based lactate dehydrogenase test for neonatal diagnostics at the point of care2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9301Article in journal (Refereed)
    Abstract [en]

    There is a growing recognition of the importance of point-of-care tests (POCTs) for detecting critical neonatal illnesses to reduce the mortality rate in newborns, especially in low-income countries, which account for 98 percent of reported neonatal deaths. Lactate dehydrogenase (LDH) is a marker of cellular damage as a result of hypoxia-ischemia in affected organs. Here, we describe and test a POC LDH test direct from whole blood to provide early indication of serious illness in the neonate. The sample-inresult- out POC platform is specifically designed to meet the needs at resource-limited settings. Plasma is separated from whole blood on filter paper with dried-down reagents for colorimetric reaction, combined with software for analysis using a smartphone. The method was clinically tested in newborns in two different settings. In a clinical cohort of newborns of Stockholm (n = 62) and Hanoi (n = 26), the value of R using Pearson's correlation test was 0.91 (p < 0.01) and the R-2 = 0.83 between the two methods. The mean LDH (+/- SD) for the reference method vs. the POC-LDH was 551 (+/- 280) U/L and 552 (+/- 249) U/L respectively, indicating the clinical value of LDH values measured in minutes with the POC was comparable with standardized laboratory analyses.

  • 158.
    Hausmann, Simon
    et al.
    Tech Univ Munich, Dept Phys, Lehrstuhl Neutronenstreuung, James Franck Str 1, D-85748 Garching, Germany..
    Ye, Jingfan
    Tech Univ Munich, Dept Phys, Lehrstuhl Neutronenstreuung, James Franck Str 1, D-85748 Garching, Germany..
    Aoki, Toshihiro
    Univ Calif Irvine, Irvine Mat Res Inst, Irvine, CA 92697 USA..
    Zheng, Jian-Guo
    Univ Calif Irvine, Irvine Mat Res Inst, Irvine, CA 92697 USA..
    Stahn, Jochen
    Paul Scherrer Inst, Lab Neutron Scattering & Imaging, CH-5232 Villigen, Switzerland..
    Bern, Francis
    Univ Leipzig, Div Superconduct & Magnetism, D-04103 Leipzig, Germany..
    Chen, Binda
    Tech Univ Munich, Dept Phys, Lehrstuhl Neutronenstreuung, James Franck Str 1, D-85748 Garching, Germany..
    Autieri, Carmine
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Esquinazi, Pablo D.
    Univ Leipzig, Div Superconduct & Magnetism, D-04103 Leipzig, Germany..
    Böni, Peter
    Tech Univ Munich, Dept Phys, Lehrstuhl Neutronenstreuung, James Franck Str 1, D-85748 Garching, Germany..
    Paul, Amitesh
    Tech Univ Munich, Dept Phys, Lehrstuhl Neutronenstreuung, James Franck Str 1, D-85748 Garching, Germany..
    Atomic-scale engineering of ferroelectric-ferromagnetic interfaces of epitaxial perovskite films for functional properties2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10734Article in journal (Refereed)
    Abstract [en]

    Besides epitaxial mismatch that can be accommodated by lattice distortions and/or octahedral rotations, ferroelectric-ferromagnetic interfaces are affected by symmetry mismatch and subsequent magnetic ordering. Here, we have investigated La-0.67 Sr-0.33 MnO3 (LSMO) samples with varying underlying unit cells (uc) of BaTiO3 (BTO) layer on (001) and (110) oriented substrates in order to elucidate the role of symmetry mismatch. Lattice mismatch for 3 uc of BTO and symmetry mismatch for 10 uc of BTO, both associated with local MnO6 octahedral distortions of the (001) LSMO within the first few uc, are revealed by scanning transmission electron microscopy. Interestingly, we find exchange bias along the in-plane [110]/[100] directions only for the (001) oriented samples. Polarized neutron reflectivity measurements confirm the existence of a layer with zero net moment only within (001) oriented samples. First principle density functional calculations show that even though the bulk ground state of LSMO is ferromagnetic, a large lattice constant together with an excess of La can stabilize an antiferromagnetic LaMnO3-type phase at the interface region and explain the experimentally observed exchange bias. Atomic scale tuning of MnO6 octahedra can thus be made possible via symmetry mismatch at heteroepitaxial interfaces. This aspect can act as a vital parameter for structure-driven control of physical properties.

  • 159.
    Hawkes, Jeffrey A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Radoman, Nikola
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Stockholm Univ, Dept Environm Sci & Analyt Chem, Stockholm, Sweden.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wallin, Marcus
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Tranvik, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Löfgren, Stefan
    Swedish Univ Agr Sci SLU, Dept Aquat Sci & Assessment, Sect Geochem & Hydrol, Uppsala, Sweden.
    Regional diversity of complex dissolved organic matter across forested hemiboreal headwater streams2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 16060Article in journal (Refereed)
    Abstract [en]

    Dissolved organic matter (DOM) from soils enters the aquatic environment via headwater streams. Thereafter, it is gradually transformed, removed by sedimentation, and mineralised. Due to the proximity to the terrestrial source and short water residence time, the extent of transformation is minimal in headwaters. DOM has variable composition across inland waters, but the amount of variability in the terrestrial end member is unknown. This gap in knowledge is crucial considering the potential impact large variability would have on modelling DOM degradation. Here, we used a novel liquid chromatography –mass spectrometry method to characterise DOM in 74 randomly selected, forested headwater streams in an 87,000 km2 region of southeast Sweden. We found a large degree of sample similarity across this region, with Bray-Curtis dissimilarity values averaging 8.4 ± 3.0% (mean ± SD). The identified variability could be reduced to two principle coordinates, correlating to varying groundwater flow-paths and regional mean temperature. Our results indicate that despite reproducible effects of groundwater geochemistry and climate, the composition of DOM is remarkably similar across catchments already as it leaves the terrestrial environment, rather than becoming homogeneous as different headwaters and sub-catchments mix.

  • 160.
    He, Liqun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Vanlandewijck, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, ICMC, SE-14157 Huddinge, Sweden..
    Raschperger, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, ICMC, SE-14157 Huddinge, Sweden..
    Mae, Maarja Andaloussi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Jung, Bongnam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Lebouvier, Thibaud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Ando, Koji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Hofmann, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Keller, Annika
    Univ Zurich, Zurich Univ Hosp, Div Neurosurg, Zurich, Switzerland..
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, ICMC, SE-14157 Huddinge, Sweden..
    Analysis of the brain mural cell transcriptome2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35108Article in journal (Refereed)
    Abstract [en]

    Pericytes, the mural cells of blood microvessels, regulate microvascular development and function and have been implicated in many brain diseases. However, due to a paucity of defining markers, pericyte identification and functional characterization remain ambiguous and data interpretation problematic. In mice carrying two transgenic reporters, Pdgfrb-eGFP and NG2-DsRed, we found that double-positive cells were vascular mural cells, while the single reporters marked additional, but non-overlapping, neuroglial cells. Double-positive cells were isolated by fluorescence-activated cell sorting (FACS) and analyzed by RNA sequencing. To reveal defining patterns of mural cell transcripts, we compared the RNA sequencing data with data from four previously published studies. The meta-analysis provided a conservative catalogue of 260 brain mural cell-enriched gene transcripts. We validated pericyte-specific expression of two novel markers, vitronectin (Vtn) and interferon-induced transmembrane protein 1 (Ifitm1), using fluorescent in situ hybridization and immunohistochemistry. We further analyzed signaling pathways and interaction networks of the pericyte-enriched genes in silico. This work provides novel insight into the molecular composition of brain mural cells. The reported gene catalogue facilitates identification of brain pericytes by providing numerous new candidate marker genes and is a rich source for new hypotheses for future studies of brain mural cell physiology and pathophysiology.

  • 161.
    He, Peng
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Hou, Xiaolin
    Aldahan, Ala
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandem Laboratory.
    Yi, Peng
    Iodine isotopes species fingerprinting environmental conditions in surface water along the northeastern Atlantic Ocean2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2685-Article in journal (Refereed)
    Abstract [en]

    Concentrations and species of iodine isotopes (I-127 and I-129) provide vital information about iodine geochemistry, environmental conditions and water masses exchange in oceans. Despite extensive investigations of anthropogenic I-129 in the Arctic Ocean and the Nordic Seas, concentrations of the isotope in the Atlantic Ocean are, however, still unknown. We here present first data on I-129 and I-127, and their species (iodide and iodate) in surface water transect along the northeastern Atlantic between 30 degrees and 50 degrees N. The results show iodate as the predominant species in the analyzed marine waters for both I-127 and I-129. Despite the rather constant ratios of I-127(-)/(IO3-)-I-127, the I-129(-)/(IO3-)-I-129 values reveal variations that apparently response to sources, environmental conditions and residence time. These findings provide a new tracer approach that will strongly enhance the application of anthropogenic I-129 in ocean environments and impact on climate at the ocean boundary layer.

  • 162.
    He, Qi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Li, Xiujuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Cyrus Tang Hematology Center, Soochow University, Suzhou, China.
    Singh, Kailash
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Luo, Zhengkang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Meija-Cordova, Mariela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jamalpour, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lindahl, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kriz, Vitezslav
    Vuolteenaho, Reetta
    Ulvmar, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Welsh, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7548Article in journal (Refereed)
    Abstract [en]

    The tamoxifen-responsive conditional Cdh5-CreERT2 is commonly used for endothelial cell specific conditional deletion of loxP-flanked gene sequences. To address the role of endothelial cell Shb gene for B16F10 melanoma immune responses, tamoxifen-injected Cdh5-CreERT2/WT and Cdh5-CreERT2/Shbflox/flox mice received subcutaneous tumor cell injections. We observed a decrease of tumor myeloid cell Shb mRNA in the tamoxifen treated Cdh5-CreERT2/Shbflox/flox mice, which was not present when the mice had undergone a preceding bone marrow transplantation using wild type bone marrow. Differences in CD4+/FoxP3+ Tregs were similarly abolished by a preceding bone marrow transplantation. In ROSA26-mTmG mice, Cdh5-CreERT2 caused detectable floxing in certain bone marrow populations and in spleen cells. Floxing in bone marrow could be detected two months after tamoxifen treatment. In the spleen, however, floxing was undetectable two months after tamoxifen treatment, suggesting that Cdh5-CreERT2 is operating in a non-renewable population of hematopoietic cells in this organ. These data suggest that conditional gene deletion in hematopoietic cells is a potential confounder in experiments attempting to assess the role of endothelial specific effects. A cautious approach to achieve an endothelial-specific phenotype would be to adopt a strategy that includes a preceding bone marrow transplantation.

  • 163.
    Henriksen, R.
    et al.
    Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
    Johnsson, M.
    Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jensen, P.
    Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
    Wright, D.
    Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
    The domesticated brain: genetics of brain mass and brain structure in an avian species2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34031Article in journal (Refereed)
    Abstract [en]

    As brain size usually increases with body size it has been assumed that the two are tightly constrained and evolutionary studies have therefore often been based on relative brain size (i.e. brain size proportional to body size) rather than absolute brain size. The process of domestication offers an excellent opportunity to disentangle the linkage between body and brain mass due to the extreme selection for increased body mass that has occurred. By breeding an intercross between domestic chicken and their wild progenitor, we address this relationship by simultaneously mapping the genes that control inter-population variation in brain mass and body mass. Loci controlling variation in brain mass and body mass have separate genetic architectures and are therefore not directly constrained. Genetic mapping of brain regions indicates that domestication has led to a larger body mass and to a lesser extent a larger absolute brain mass in chickens, mainly due to enlargement of the cerebellum. Domestication has traditionally been linked to brain mass regression, based on measurements of relative brain mass, which confounds the large body mass augmentation due to domestication. Our results refute this concept in the chicken.

  • 164.
    Henriques, Dora
    et al.
    Polytech Inst Braganca, Mt Res Ctr CIMO, Campus Sta Apolonia, P-5300253 Braganca, Portugal;Univ Minho, Ctr Mol & Environm Biol CBMA, Campus Gualtar, P-4710057 Braga, Portugal.
    Wallberg, Andreas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Chavez-Galarza, Julio
    Inst Nacl Innovac Agr, Av La Molina 1981, Lima, Peru;Polytech Inst Braganca, Mt Res Ctr CIMO, Campus Sta Apolonia, P-5300253 Braganca, Portugal.
    Johnston, J. Spencer
    Texas A&M Univ, Dept Entomol, College Stn, TX 77843 USA.
    Webster, Matthew Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alice Pinto, M.
    Polytech Inst Braganca, Mt Res Ctr CIMO, Campus Sta Apolonia, P-5300253 Braganca, Portugal.
    Whole genome SNP-associated signatures of local adaptation in honeybees of the Iberian Peninsula2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11145Article in journal (Refereed)
    Abstract [en]

    The availability of powerful high-throughput genomic tools, combined with genome scans, has helped identifying genes and genetic changes responsible for environmental adaptation in many organisms, including the honeybee. Here, we resequenced 87 whole genomes of the honeybee native to Iberia and used conceptually different selection methods (Sam beta ada, LFMM, PCAdapt, iHs) together with in sillico protein modelling to search for selection footprints along environmental gradients. We found 670 outlier SNPs, most of which associated with precipitation, longitude and latitude. Over 88.7% SNPs laid outside exons and there was a significant enrichment in regions adjacent to exons and UTRs. Enrichment was also detected in exonic regions. Furthermore, in silico protein modelling suggests that several non-synonymous SNPs are likely direct targets of selection, as they lead to amino acid replacements in functionally important sites of proteins. We identified genomic signatures of local adaptation in 140 genes, many of which are putatively implicated in fitness-related functions such as reproduction, immunity, olfaction, lipid biosynthesis and circadian clock. Our genome scan suggests that local adaptation in the Iberian honeybee involves variations in regions that might alter patterns of gene expression and in protein-coding genes, which are promising candidates to underpin adaptive change in the honeybee.

  • 165.
    Herman, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4129Article in journal (Refereed)
    Abstract [en]

    Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

  • 166.
    Hernández Vera, Rodrigo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    O'Callaghan, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fatsis-Kavalopoulos, Nikos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Gradientech AB, Uppsala Science Park, Uppsala, Sweden.
    Kreuger, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Modular microfluidic systems cast from 3D-printed molds for imaging leukocyte adherence to differentially treated endothelial cultures2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11321Article in journal (Refereed)
    Abstract [en]

    Microfluidic systems are very useful for in vitro studies of interactions between blood cells and vascular endothelial cells under flow, and several commercial solutions exist. However, the availability of customizable, user-designed devices is largely restricted to researchers with expertise in photolithography and access to clean room facilities. Here we describe a strategy for producing tailor-made modular microfluidic systems, cast in PDMS from 3D-printed molds, to facilitate studies of leukocyte adherence to endothelial cells. A dual-chamber barrier module was optimized for culturing two endothelial cell populations, separated by a 250 μm wide dividing wall, on a glass slide. In proof-of-principle experiments one endothelial population was activated by TNFα, while the other served as an internal control. The barrier module was thereafter replaced with a microfluidic flow module, enclosing both endothelial populations in a common channel. A suspension of fluorescently-labeled leukocytes was then perfused through the flow module and leukocyte interactions with control and tnfα-treated endothelial populations were monitored in the same field of view. Time-lapse microscopy analysis confirmed the preferential attachment of leukocytes to the TNFα-activated endothelial cells. We conclude that the functionality of these modular microfluidic systems makes it possible to seed and differentially activate adherent cell types, and conduct controlled side-by-side analysis of their capacity to interact with cells in suspension under flow. Furthermore, we outline a number of practical considerations and solutions associated with connecting and switching between the microfluidic modules, and the advantages of simultaneously and symmetrically analyzing control and experimental conditions in such a microfluidic system.

  • 167.
    Hervella, M.
    et al.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Svensson, Emma M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Alberdi, A.
    Univ Copenhagen, Nat Hist Museum Denmark, Oster Voldgade 5-7, DK-1350 Copenhagen, Denmark..
    Günther, Torsten
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Izagirre, N.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Munters, Arielle R.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Alonso, S.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Ioana, M.
    Univ Med & Pharm Craiova, Human Genom Lab, Bvd 1 Mai 66, Craiova, Romania.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands..
    Ridiche, F.
    Museum Oltenia, Hist & Archaeol Dept, Madona Dudu Str 14, Craiova, Romania..
    Soficaru, A.
    Romanian Acad, Fr J Rainer Inst Anthropol, Eroii Sanitari 8,POB 35-13, Bucharest, Romania..
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Netea, M. G.
    Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands..
    de-la-Rua, C.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25501Article in journal (Refereed)
    Abstract [en]

    After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Pestera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages.

  • 168.
    Hetenyi, Gyorgy
    et al.
    Univ Lausanne, Inst Earth Sci, Geopolis, Quartier UNIL Mouline, CH-1015 Lausanne, Switzerland.;ETH, Dept Earth Sci, Soneggstr 5, CH-8092 Zurich, Switzerland.;Ecole Normale Super, CNRS, Geol Lab, UMR 8538, 24 Rue Lhomond, F-75005 Paris, France..
    Cattin, Rodolphe
    Ecole Normale Super, CNRS, Geol Lab, UMR 8538, 24 Rue Lhomond, F-75005 Paris, France.;Univ Montpellier, CNRS UMR5243, Geosci Montpellier, Pl E Bataillon, F-34095 Montpellier, France..
    Berthet, Theo
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Le Moigne, Nicolas
    Univ Montpellier, CNRS UMR5243, Geosci Montpellier, Pl E Bataillon, F-34095 Montpellier, France..
    Chophel, Jamyang
    Minist Econ Affairs, Dept Geol & Mines, POB 173, Thimphu, Bhutan..
    Lechmann, Sarah
    ETH, Dept Earth Sci, Soneggstr 5, CH-8092 Zurich, Switzerland.;Fed Dept Def Civil Protect & Sport, Armasuisse Sci & Technol, Feuerwerkerstr 39, CH-3602 Thun, Switzerland..
    Hammer, Paul
    ETH, Dept Earth Sci, Soneggstr 5, CH-8092 Zurich, Switzerland.;SwissRe, Mythenquai 50-60, CH-8022 Zurich, Switzerland..
    Drukpa, Dowchu
    Minist Econ Affairs, Dept Geol & Mines, POB 173, Thimphu, Bhutan..
    Sapkota, Soma Nath
    Dept Mines & Geol, Kathmandu, Nepal..
    Gautier, Stephanie
    Univ Montpellier, CNRS UMR5243, Geosci Montpellier, Pl E Bataillon, F-34095 Montpellier, France..
    Thinley, Kinzang
    Natl Land Commiss, POB 142, Kawang Jagsa, Thimphu, Bhutan..
    Segmentation of the Himalayas as revealed by arc-parallel gravity anomalies2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 33866Article in journal (Refereed)
    Abstract [en]

    Lateral variations along the Himalayan arc are suggested by an increasing number of studies and carry important information about the orogen's segmentation. Here we compile the hitherto most complete land gravity dataset in the region which enables the currently highest resolution plausible analysis. To study lateral variations in collisional structure we compute arc-parallel gravity anomalies (APaGA) by subtracting the average arc-perpendicular profile from our dataset; we compute likewise for topography (APaTA). We find no direct correlation between APaGA, APaTA and background seismicity, as suggested in oceanic subduction context. In the Himalayas APaTA mainly reflect relief and erosional effects, whereas APaGA reflect the deep structure of the orogen with clear lateral boundaries. Four segments are outlined and have disparate flexural geometry: NE India, Bhutan, Nepal & India until Dehradun, and NW India. The segment boundaries in the India plate are related to inherited structures, and the boundaries of the Shillong block are highlighted by seismic activity. We find that large earthquakes of the past millennium do not propagate across the segment boundaries defined by APaGA, therefore these seem to set limits for potential rupture of megathrust earthquakes.

  • 169.
    Hildebrand, Sebastian
    et al.
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet and Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Sweden.;Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    Hultin, Sara
    Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    Subramani, Aravindh
    Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    Petropoulos, Sophie
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet and Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Sweden.
    Zhang, Yuanyuan
    Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    Cao, Xiaofang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mpindi, John
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
    Kalloniemi, Olli
    Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Majumdar, Arindam
    Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    Lanner, Fredrik
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet and Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Sweden.
    Holmgren, Lars
    Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
    The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 9540Article in journal (Refereed)
    Abstract [en]

    Epithelial cells connect via cell-cell junctions to form sheets of cells with separate cellular compartments. These cellular connections are essential for the generation of cellular forms and shapes consistent with organ function. Tissue modulation is dependent on the fine-tuning of mechanical forces that are transmitted in part through the actin connection to E-cadherin as well as other components in the adherens junctions. In this report we show that p100 amotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells over multiple layers. Genetic inactivation or depletion of amotL2 in epithelial cells in vitro or zebrafish and mouse in vivo, resulted in the loss of contractile actin filaments and perturbed epithelial packing geometry. We further showed that AMOTL2 mRNA and protein was expressed in the trophectoderm of human and mouse blastocysts. Genetic inactivation of amotL2 did not affect cellular differentiation but blocked hatching of the blastocysts from the zona pellucida. These results were mimicked by treatment with the myosin II inhibitor blebbistatin. We propose that the tension generated by the E-cadherin/AmotL2/actin filaments plays a crucial role in developmental processes such as epithelial geometrical packing as well as generation of forces required for blastocyst hatching.

  • 170.
    Hoeber, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Trolle, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    König, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Du, Zhongwei
    Gallo, Alessandro
    Hermans, Emmanuel
    Aldskogius, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Shortland, Peter
    Zhang, Su-Chun
    Deumens, Ronald
    Kozlova, Elena N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10666Article in journal (Refereed)
    Abstract [en]

    Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.

  • 171.
    Honarvar, Hadis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Calce, Enrica
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Doti, Nunzianna
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Langella, Emma
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Buijs, Jos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    D'Amato, Valentina
    Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy..
    Bianco, Roberto
    Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy..
    Saviano, Michele
    CNR, Inst Crystallog, Bari, Italy..
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    De Luca, Stefania
    CNR, Inst Biostruct & Bioimaging, Naples, Italy..
    Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 2998Article in journal (Refereed)
    Abstract [en]

    HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies. In this study, we evaluated a potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab portion. Its cellular uptake was investigated by mass spectrometry analysis of the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA chelator was conjugated to N-terminus of A9. In-111-labeled A9 demonstrated nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution profile in NMRI mice. This study suggests that the peptide A9 represents a good lead candidate for development of molecular probe, to be used for imaging purposes and for the delivery of cytotoxic agents.

  • 172.
    Horie, Masafumi
    et al.
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan..
    Yamaguchi, Yoko
    Nihon Univ, Sch Dent, Dept Biochem, Chiyoda Ku, 1-8-13 Kanda Surugadai, Tokyo 1018310, Japan.;Nihon Univ, Sch Dent, Dent Res Ctr, Div Funct Morphol,Chiyoda Ku, 1-8-13 Kanda Surugadai, Tokyo 1018310, Japan..
    Saito, Akira
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan..
    Nagase, Takahide
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan..
    Lizio, Marina
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan..
    Itoh, Masayoshi
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Prevent Med & Diag Innovat Program, 2-1 Hirosawa, Wako, Saitama 3510198, Japan..
    Kawaji, Hideya
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Prevent Med & Diag Innovat Program, 2-1 Hirosawa, Wako, Saitama 3510198, Japan..
    Lassmann, Timo
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan..
    Carninci, Piero
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan..
    Forrest, Alistair R. R.
    RIKEN Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;Univ Western Australia, Harry Perkins Inst Med Res, QEII Med Ctr, Nedlands, WA, Australia.;Univ Western Australia, Med Res Ctr, Nedlands, WA, Australia..
    Hayashizaki, Yoshihide
    RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.;RIKEN Prevent Med & Diag Innovat Program, 2-1 Hirosawa, Wako, Saitama 3510198, Japan..
    Suzutani, Tatsuo
    Fukushima Med Univ, Sch Med, Dept Microbiol, 1 Hikariga Oka, Fukushima, Fukushima 9601295, Japan..
    Kappert, Kai
    Charite, Inst Lab Med Clin Chem & Pathobiochem, Cardiovasc Res Ctr, Berlin, Germany..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ohshima, Mitsuhiro
    Ohu Univ, Sch Pharmaceut Sci, Dept Biochem, Misumido 31-1, Koriyama, Fukushima 9638611, Japan..
    Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 33666Article in journal (Refereed)
    Abstract [en]

    Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.

  • 173.
    Hornung, Roman
    et al.
    Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany.
    Jurinovic, Vindi
    Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany.
    Batcha, Aarif M. N.
    Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany;German Canc Consortium DKTK, Partner Site Munich, Munich, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Bamopoulos, Stefanos A.
    Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany.
    Rothenberg-Thurley, Maja
    Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany.
    Amler, Susanne
    Univ Munster, Inst Biostat & Clin Res, Munster, Germany.
    Sauerlands, Maria Cristina
    Univ Munster, Inst Biostat & Clin Res, Munster, Germany.
    Berdel, Wolfgang E.
    Univ Munster, Dept Med Hematol & Oncol A, Munster, Germany.
    Woermann, Bernhard J.
    German Soc Hematol & Oncol, Berlin, Germany.
    Bohlander, Stefan K.
    Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand.
    Braess, Jan
    Hosp Barmherzige Bruder, Dept Oncol & Hematol, Regensburg, Germany.
    Hiddemann, Wolfgang
    German Canc Consortium DKTK, Partner Site Munich, Munich, Germany;Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Lehmann, Sören
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Karolinska Inst, Dept Med, Stockholm, Sweden.
    Mareschal, Sylvain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Spiekermann, Karsten
    German Canc Consortium DKTK, Partner Site Munich, Munich, Germany;Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Metzeler, Klaus H.
    German Canc Consortium DKTK, Partner Site Munich, Munich, Germany;Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Herold, Tobias
    German Canc Consortium DKTK, Partner Site Munich, Munich, Germany;Ludwig Maximilians Univ Munchen, Dept Med 3, Univ Hosp, Munich, Germany;German Canc Res Ctr, Heidelberg, Germany.
    Boulesteix, Anne-Laure
    Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany.
    Mediation analysis reveals common mechanisms of RUNX1 point mutations and RUNX1/RUNX1T1 fusions influencing survival of patients with acute myeloid leukemia2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11293Article in journal (Refereed)
    Abstract [en]

    Alterations of RUNX1 in acute myeloid leukemia (AML) are associated with either a more favorable outcome in the case of the RUNX1/RUNX1T1 fusion or unfavorable prognosis in the case of point mutations. In this project we aimed to identify genes responsible for the observed differences in outcome that are common to both RUNX1 alterations. Analyzing four AML gene expression data sets (n = 1514), a total of 80 patients with RUNX1/RUNX1T1 and 156 patients with point mutations in RUNX1 were compared. Using the statistical tool of mediation analysis we identified the genes CD109, HOPX, and KIAA0125 as candidates for mediator genes. In an analysis of an independent validation cohort, KIAA0125 again showed a significant influence with respect to the impact of the RUNX1/RUNX1T1 fusion. While there were no significant results for the other two genes in this smaller validation cohort, the observed relations linked with mediation effects (i.e., those between alterations, gene expression and survival) were almost without exception as strong as in the main analysis. Our analysis demonstrates that mediation analysis is a powerful tool in the identification of regulative networks in AML subgroups and could be further used to characterize the influence of genetic alterations.

  • 174. Hosen, M. Mofazzel
    et al.
    Dhakal, Gyanendra
    Dimitri, Klauss
    Maldonado, Pablo
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Aperis, Alex
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Kabir, Firoza
    Sims, Christopher
    Riseborough, Peter
    Oppeneer, Peter M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Kaczorowski, Dariusz
    Durakiewicz, Tomasz
    Neupane, Madhab
    Discovery of topological nodal-line fermionic phase in a magnetic material GdSbTe2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 13283Article in journal (Refereed)
    Abstract [en]

    Topological Dirac semimetals with accidental band touching between conduction and valence bands protected by time reversal and inversion symmetry are at the frontier of modern condensed matter research. A majority of discovered topological semimetals are nonmagnetic and conserve time reversal symmetry. Here we report the experimental discovery of an antiferromagnetic topological nodal-line semimetallic state in GdSbTe using angle-resolved photoemission spectroscopy. Our systematic study reveals the detailed electronic structure of the paramagnetic state of antiferromagnetic GdSbTe. We observe the presence of multiple Fermi surface pockets including a diamond-shape, and small circular pockets around the zone center and high symmetry X points of the Brillouin zone (BZ), respectively. Furthermore, we observe the presence of a Dirac-like state at the X point of the BZ and the effect of magnetism along the nodal-line direction. Interestingly, our experimental data show a robust  Dirac-like state both below and above the magnetic transition temperature (TN  = 13 K). Having a relatively high transition temperature, GdSbTe provides an archetypical platform to study the interaction between magnetism and topological states of matter.

  • 175.
    Huang, Shuo
    et al.
    Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden.
    Li, Wei
    Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden.
    Holmström, Erik
    Sandvik Coromant R&D, S-12680 Stockholm, Sweden.
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden; Inst Solid State Phys & Opt, Wigner Res Ctr Phys, H-1525 Budapest, Hungary.
    Phase-transition assisted mechanical behavior of TiZrHfTax high-entropy alloys2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12576Article in journal (Refereed)
    Abstract [en]

    Recent developments of high-entropy alloys with high strength and high ductility draw attention to the metastability-engineering strategy. Using first-principle theory, here we demonstrate that reducing the Ta level in the refractory TiZrHfTax system destabilizes the body-centered cubic (bcc) phase and leads to the appearance of the hexagonal close-packed (hcp) phase embedded in the bcc matrix. The alloying-induced features of the elastic parameters for the cubic and hexagonal structures are mapped out in details, and strong sensitivity to the crystal lattice and chemistry is revealed. Results show softening of the bcc matrix with decreasing Ta concentration which ensures ductile behavior. However, the elastically nearly isotropic hcp precipitates possess enhanced resistance against shear which promotes strengthening of the TiZrHfTax dual-phase system. The present atomic-level insight provides strong evidence to the experimental observation, and emphasizes the significance of quantum-design for advanced multi-phase high-entropy alloys with excellent strength-ductility combinations.

  • 176.
    Hudl, Matthias
    et al.
    Stockholm Univ, Dept Phys, Chem Phys, SE-10691 Stockholm, Sweden..
    Mathieu, Roland
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Nordblad, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Tunable exchange bias in dilute magnetic alloys: chiral spin glasses2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19964Article in journal (Refereed)
    Abstract [en]

    A unidirectional anisotropy appears in field cooled samples of dilute magnetic alloys at temperatures well below the cusp temperature of the zero field cooled magnetization curve. Magnetization measurements on a Cu(13.5 at% Mn) sample show that this anisotropy is essentially temperature independent and acts on a temperature dependent excess magnetization, Delta M. The anisotropy can be partially or fully transferred from being locked to the direction of the cooling field at lower fields to becoming locked to the direction of Delta M at larger fields, thus instead appearing as a uniaxial anisotropy. This introduces a deceiving division of the anisotropy into a superposition of a unidirectional and a uniaxial part. This two faced nature of the anisotropy has been empirically scrutinized and concluded to originate from one and the same exchange mechanism: the Dzyaloshinsky-Moriya interaction.

  • 177.
    Hulme, Heather E.
    et al.
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Meikle, Lynsey M.
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Wessel, Hannah
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Strittmatter, Nicole
    AstraZeneca, Milton Sci Pk, Cambridge CB4 0WG, England..
    Swales, John
    AstraZeneca, Milton Sci Pk, Cambridge CB4 0WG, England..
    Thomson, Carolyn
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nibbs, Robert J. B.
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Milling, Simon
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mackay, C. Logan
    Univ Edinburgh, Sch Chem, Edinburgh EH9 3FJ, Midlothian, Scotland..
    Dexter, Alex
    Natl Phys Lab, Teddington TW11 0LW, Middx, England..
    Bunch, Josephine
    Natl Phys Lab, Teddington TW11 0LW, Middx, England..
    Goodwin, Richard J. A.
    AstraZeneca, Milton Sci Pk, Cambridge CB4 0WG, England..
    Burchmore, Richard
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Wall, Daniel M.
    Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland..
    Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2786Article in journal (Refereed)
    Abstract [en]

    Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169(+) sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4(+) CD25(+) T cells and an increased number of B220(+) CD19(+) B cells. The reduction in CD4(+) CD25(+) T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome.

  • 178.
    Husain, Sajid
    et al.
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India..
    Akansel, Serkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Kumar, Ankit
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Svedlindh, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Chaudhary, Sujeet
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India..
    Growth of Co2FeAl Heusler alloy thin films on Si(100) having very small Gilbert damping by Ion beam sputtering2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 28692Article in journal (Refereed)
    Abstract [en]

    The influence of growth temperature T-s (300-773 K) on the structural phase ordering, static and dynamic magnetization behaviour has been investigated in ion beam sputtered full Heusler alloy Co2FeAl (CFA) thin films on industrially important Si(100) substrate. The B2 type magnetic ordering is established in these films based on the clear observation of the (200) diffraction peak. These ion beam sputtered CFA films possess very small surface roughness of the order of subatomic dimensions (<3 angstrom) as determined from the fitting of XRR spectra and also by AFM imaging. This is supported by the occurrence of distinct Kiessig fringes spanning over the whole scanning range (similar to 4 degrees) in the x-ray reflectivity (XRR) spectra. The Gilbert damping constant alpha and effective magnetization 4 pi M-eff are found to vary from 0.0053 +/- 0.0002 to 0.0015 +/- 0.0001 and 13.45 +/- 00.03 kG to 14.03 +/- 0.04 kG, respectively. These Co2FeAl films possess saturation magnetization ranging from 4.82 +/- 0.09 to 5.22 +/- 0.10 mu(B)/f.u. consistent with the bulk L2(1)-type ordering. A record low alpha-value of 0.0015 is obtained for Co2FeAl films deposited on Si substrate at T-s similar to 573 K.

  • 179.
    Husain, Sajid
    et al.
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India.
    Sisodia, Naveen
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India.
    Chaurasiya, Avinash Kumar
    SN Bose Natl Ctr Basic Sci, Dept Condensed Matter Phys & Mat Sci, Block JD,Sect 3, Kolkata 700106, India.
    Kumar, Ankit
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Singh, Jitendra Pal
    Yadav, Brajesh S.
    Solid State Phys Lab, Lucknow Rd, Delhi 110054, India.
    Akansel, Serkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Chae, Keun Hwa
    Korea Inst Sci & Technol, Adv Anal Ctr, Seoul 02792, South Korea.
    Barman, Anjan
    SN Bose Natl Ctr Basic Sci, Dept Condensed Matter Phys & Mat Sci, Block JD,Sect 3, Kolkata 700106, India.
    Muduli, P. K.
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India.
    Svedlindh, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Chaudhary, Sujeet
    Indian Inst Technol Delhi, Dept Phys, Thin Film Lab, New Delhi 110016, India.
    Observation of Skyrmions at Room Temperature in Co2FeAl Heusler Alloy Ultrathin Film Heterostructures2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1085Article in journal (Refereed)
    Abstract [en]

    Magnetic skyrmions are topological spin-textures having immense potential for energy efficient spintronic devices. Here, we report the observation of stable skyrmions in unpatterned Ta/Co2FeAl(CFA)/MgO thin film heterostructures at room temperature in remnant state employing magnetic force microscopy. It is shown that these skyrmions consisting of ultrathin ferromagnetic CFA Heusler alloy result from strong interfacial Dzyaloshinskii-Moriya interaction (i-DMI) as evidenced by Brillouin light scattering measurements, in agreement with the results of micromagnetic simulations. We also emphasize on room temperature observation of multiple skyrmions which can be stabilized for suitable combinations of CFA layer thickness, perpendicular magnetic anisotropy, and i-DMI. These results provide a significant step towards designing of room temperature spintronic devices based on skyrmions in full Heusler alloy based thin films.

  • 180.
    Ilari, Andrea
    et al.
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Fiorillo, Annarita
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Poser, Elena
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Lalioti, Vasiliki S.
    Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Celular & Inmunol, Canto Blanco, Spain.;Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain..
    Sundell, Gustav N.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Ivarsson, Ylva
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden..
    Genovese, Ilaria
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Colotti, Gianni
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Structural basis of Sorcin-mediated calcium-dependent signal transduction2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16828Article in journal (Refereed)
    Abstract [en]

    Sorcin is an essential penta-EF hand calcium binding protein, able to confer the multi-drug resistance phenotype to drug-sensitive cancer cells and to reduce Endoplasmic Reticulum stress and cell death. Sorcin silencing blocks cell cycle progression in mitosis and induces cell death by triggering apoptosis. Sorcin participates in the modulation of calcium homeostasis and in calcium-dependent cell signalling in normal and cancer cells. The molecular basis of Sorcin action is yet unknown. The X-ray structures of Sorcin in the apo (apoSor) and in calcium bound form (CaSor) reveal the structural basis of Sorcin action: calcium binding to the EF1-3 hands promotes a large conformational change, involving a movement of the long D-helix joining the EF1-EF2 sub-domain to EF3 and the opening of EF1. This movement promotes the exposure of a hydrophobic pocket, which can accommodate in CaSor the portion of its N-terminal domain displaying the consensus binding motif identified by phage display experiments. This domain inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin consensus motif, co-localizes with Sorcin in the perinuclear region of the cell and in the midbody and is involved in the onset of apoptosis.

  • 181.
    Ilari, Andrea
    et al.
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Fiorillo, Annarita
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Poser, Elena
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Lalioti, Vasiliki S.
    Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Celular & Inmunol, Canto Blanco, Spain.;Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain..
    Sundell, Gustav N.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Ivarsson, Ylva
    Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden..
    Genovese, Ilaria
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Colotti, Gianni
    Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy.;Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy..
    Structural basis of Sorcin-mediated calcium-dependent signal transduction2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16828Article in journal (Refereed)
    Abstract [en]

    Sorcin is an essential penta-EF hand calcium binding protein, able to confer the multi-drug resistance phenotype to drug-sensitive cancer cells and to reduce Endoplasmic Reticulum stress and cell death. Sorcin silencing blocks cell cycle progression in mitosis and induces cell death by triggering apoptosis. Sorcin participates in the modulation of calcium homeostasis and in calcium-dependent cell signalling in normal and cancer cells. The molecular basis of Sorcin action is yet unknown. The X-ray structures of Sorcin in the apo (apoSor) and in calcium bound form (CaSor) reveal the structural basis of Sorcin action: calcium binding to the EF1-3 hands promotes a large conformational change, involving a movement of the long D-helix joining the EF1-EF2 sub-domain to EF3 and the opening of EF1. This movement promotes the exposure of a hydrophobic pocket, which can accommodate in CaSor the portion of its N-terminal domain displaying the consensus binding motif identified by phage display experiments. This domain inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin consensus motif, co-localizes with Sorcin in the perinuclear region of the cell and in the midbody and is involved in the onset of apoptosis.

  • 182.
    Iliadis, Stavros I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Axfors, Cathrine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Johansson, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Mulic-Lutvica, Ajlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Women with prolonged nausea in pregnancy have increased risk for depressive symptoms postpartum2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 15796Article in journal (Refereed)
    Abstract [en]

    The aim of this population-based, longitudinal study was to assess the association between nausea and vomiting in pregnancy (NVP) and perinatal depressive symptoms. Pregnant women (N = 4239) undergoing routine ultrasound at gestational week (GW) 17 self-reported on NVP and were divided into those without nausea (G0), early (<= 17 GW) nausea without medication (G1), early nausea with medication (G2), and prolonged (>17 GW) nausea (G3). The Edinburgh Postnatal Depression Scale at GW 17 and 32 (cut-off >= 13) and at six weeks postpartum (cut-off >= 12) was used to assess depressive symptoms. Main outcome measures were depressive symptoms at GW 32 and at six weeks postpartum. NVP was experienced by 80.7%. The unadjusted logistic regression showed a positive association between all three nausea groups and depressive symptoms at all time-points. After adjustment, significant associations with postpartum depressive symptoms remained for G3, compared to G0 (aOR = 1.66; 95% CI 1.1-2.52). After excluding women with history of depression, only the G3 group was at higher odds for postpartum depressive symptoms (aOR = 2.26; 95% CI 1.04-4.92). In conclusion, women with prolonged nausea have increased risk of depressive symptoms at six weeks postpartum, regardless of history of depression.

  • 183.
    Ishibashi, Ryoichi
    et al.
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Takemoto, Minoru
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Akimoto, Yoshihiro
    Kyorin Univ, Sch Med, Dept Anat, Mitaka, Tokyo 181, Japan..
    Ishikawa, Takahiro
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    He, Peng
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan..
    Maezawa, Yoshiro
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Sakamoto, Kenichi
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Tsurutani, Yuya
    Yokohama Rosai Hosp, Yokohama, Kanagawa, Japan..
    Ide, Shintaro
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Ide, Kana
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Kawamura, Harukiyo
    Eastern Chiba Med Ctr, Chiba, Japan..
    Kobayashi, Kazuki
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Tokuyama, Hirotake
    Yu Karigaoka Tokuyama Clin, Chiba, Japan..
    Tryggvason, Karl
    Duke NUS Grad Med Sch, Cardiovasc & Metab Disorders Program, Singapore, Singapore..
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Yokote, Koutaro
    Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan.;Chiba Univ Hosp, Div Diabet Metab & Endocrinol, Chiba, Japan..
    A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25955Article in journal (Refereed)
    Abstract [en]

    Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the pathophysiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

  • 184.
    Isidorova, Anastasija
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Grasset, Charlotte
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Mendonca, Raquel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Methane formation in tropical reservoirs predicted from sediment age and nitrogen2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11017Article in journal (Refereed)
    Abstract [en]

    Freshwater reservoirs, in particular tropical ones, are an important source of methane (CH4) to the atmosphere, but current estimates are uncertain. The CH4 emitted from reservoirs is microbially produced in their sediments, but at present, the rate of CH4 formation in reservoir sediments cannot be predicted from sediment characteristics, limiting our understanding of reservoir CH4 emission. Here we show through a long-term incubation experiment that the CH4 formation rate in sediments of widely different tropical reservoirs can be predicted from sediment age and total nitrogen concentration. CH4 formation occurs predominantly in sediment layers younger than 6-12 years and beyond these layers sediment organic carbon may be considered effectively buried. Hence mitigating reservoir CH4 emission via improving nutrient management and thus reducing organic matter supply to sediments is within reach. Our model of sediment CH4 formation represents a first step towards constraining reservoir CH4 emission from sediment characteristics.

  • 185.
    Islam, Md. Koushikul
    et al.
    Umea Univ, Dept Clin Microbiol, Infect Dis, Umea, Sweden..
    Strand, Mårten
    Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden..
    Saleeb, Michael
    Umea Univ, Dept Chem, Umea, Sweden..
    Svensson, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Baranczewski, Pawel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Artursson, Per
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Wadell, Göran
    Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden..
    Ahlm, Clas
    Umea Univ, Dept Clin Microbiol, Infect Dis, Umea, Sweden..
    Elofsson, Mikael
    Umea Univ, Dept Chem, Umea, Sweden..
    Evander, Magnus
    Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden..
    Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1925Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.

  • 186. Jacobsen, Carsten Suhr
    et al.
    Nielsen, Tue Kjærgaard
    Vester, Jan Kjølhede
    Stougaard, Peter
    Nielsen, Jeppe Lund
    Voriskova, Jana
    Winding, Anne
    Baldrian, Petr
    Liu, Binbin
    Frostegård, Åsa
    Pedersen, Dorthe
    Tveit, Alexander Tøsdal
    Svenning, Mette Marianne
    Tebbe, Christoph C.
    Øvreås, Lise
    Jakobsen, Pia Bach
    Blazewicz, Steven J.
    Hubablek, Valerie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hansen, Lars Hestbjerg
    Cary, S. Craig
    Holben, William E.
    Ekelund, Flemming
    Bælum, Jacob
    Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5711Article in journal (Refereed)
    Abstract [en]

    Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.

  • 187.
    Jacobsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Andersson, Håkan S.
    Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, Kalmar, Sweden..
    Strand, Malin
    Swedish Univ Agr Sci, Swedish Species Informat Ctr, Uppsala, Sweden..
    Peigneur, Steve
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Eriksson, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Lodén, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Shariatgorji, Mohammadreza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lebbe, Eline K. M.
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Rosengren, K. Johan
    Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia..
    Tytgat, Jan
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Göransson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Peptide ion channel toxins from the bootlace worm, the longest animal on Earth2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4596Article in journal (Refereed)
    Abstract [en]

    Polypeptides from animal venoms have found important uses as drugs, pharmacological tools, and within biotechnological and agricultural applications. We here report a novel family of cystine knot peptides from nemertean worms, with potent activity on voltage-gated sodium channels. These toxins, named the alpha-nemertides, were discovered in the epidermal mucus of Lineus longissimus, the 'bootlace worm' known as the longest animal on earth. The most abundant peptide, the 31-residue long alpha-1, was isolated, synthesized, and its 3D NMR structure determined. Transcriptome analysis including 17 species revealed eight alpha-nemertides, mainly distributed in the genus Lineus. alpha-1 caused paralysis and death in green crabs (Carcinus maenas) at 1 mu g/kg (similar to 300 pmol/kg). It showed profound effect on invertebrate voltage-gated sodium channels (e.g. Blattella germanica Na(v)1) at low nanomolar concentrations. Strong selectivity for insect over human sodium channels indicates that a-nemertides can be promising candidates for development of bioinsecticidal agents.

  • 188.
    Jafri, S. Hassan M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Department of Electrical Engineering, Mirpur University of Science and Technology, Pakistan.
    Löfås, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. Uppsala Univ, Dept Phys & Astron, SE-75120 Uppsala, Sweden..
    Blom, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Grigoriev, Anton
    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.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Uppsala Univ, Dept Chem BMC, SE-75123 Uppsala, Sweden..
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Nano-fabrication of molecular electronic junctions by targeted modification of metal-molecule bonds2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 14431Article in journal (Refereed)
    Abstract [en]

    Reproducibility, stability and the coupling between electrical and molecular properties are central challenges in the field of molecular electronics. The field not only needs devices that fulfill these criteria but they also need to be up-scalable to application size. In this work, few-molecule based electronics devices with reproducible electrical characteristics are demonstrated. Our previously reported 5 nm gold nanoparticles (AuNP) coated with omega-triphenylmethyl (trityl) protected 1,8-octanedithiol molecules are trapped in between sub-20 nm gap spacing gold nanoelectrodes forming AuNP-molecule network. When the trityl groups are removed, reproducible devices and stable Au-thiol junctions are established on both ends of the alkane segment. The resistance of more than 50 devices is reduced by orders of magnitude as well as a reduction of the spread in the resistance histogram is observed. By density functional theory calculations the orders of magnitude decrease in resistance can be explained and supported by TEM observations thus indicating that the resistance changes and strongly improved resistance spread are related to the establishment of reproducible and stable metal-molecule bonds. The same experimental sequence is carried out using 1,6-hexanedithiol functionalized AuNPs. The average resistances as a function of molecular length, demonstrated herein, are comparable to the one found in single molecule devices.

  • 189.
    Jendresen, Charlotte
    et al.
    Univ Oslo, Dept Pharmacol, Postboks 1057, NO-0316 Oslo, Norway;Oslo Univ Hosp, Postboks 1057, NO-0316 Oslo, Norway.
    Digre, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Cui, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. College of Life Science, Jiangxi Normal University, Nanchang, 330022, China.
    Zhang, Xiao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Vlodavsky, Israel
    Technion, Fac Med, Canc & Vasc Biol Res Ctr Rappaport, POB 9649, IL-31096 Haifa, Israel.
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Nilsson, Lars N. G.
    Univ Oslo, Dept Pharmacol, Postboks 1057, NO-0316 Oslo, Norway;Oslo Univ Hosp, Postboks 1057, NO-0316 Oslo, Norway.
    Systemic LPS-induced A beta-solubilization and clearance in A beta PP-transgenic mice is diminished by heparanase overexpression2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4600Article in journal (Refereed)
    Abstract [en]

    Amyloid-beta (A(beta) is the main constituent of amyloid deposits in Alzheimer's disease (AD). The neuropathology is associated with neuroinflammation. Here, we investigated effects of systemic lipopolysaccharide (LPS)-treatment on neuroinflammation and A beta deposition in A beta PP-mice and doubletransgenic mice with brain expression of A beta PP and heparanase, an enzyme that degrades HS and generates an attenuated LPS-response. At 13 months of age, the mice received a single intraperitoneal injection of 50 mu g LPS or vehicle, and were sacrificed 1.5 months thereafter. A beta in the brain was analyzed histologically and biochemically after sequential detergent extraction. Neuroinflammation was assessed by CD45 immunostaining and mesoscale cytokine/chemokine ELISA. In single-transgenic mice, LPS-treatment reduced total A beta deposition and increased Tween-soluble A beta. This was associated with a reduced CXCL1, IL-1 beta, TNF-alpha-level and microgliosis, which correlated with amyloid deposition and total A beta. In contrast, LPS did not change A beta accumulation or inflammation marker in the doubletransgenic mice. Our findings suggest that a single pro-inflammatory LPS-stimulus, if given sufficient time to act, triggers A beta-clearance in A beta PP-transgenic mouse brain. The effects depend on HS and heparanase.

  • 190.
    Jeong, Seung Hee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Chen, Si
    Chalmers, Dept Microtechnol & Nanosci MC2, SE-41296 Gothenburg, Sweden..
    Huo, Jinxing
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Gamstedt, Erik Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Liu, Johan
    Chalmers, Dept Microtechnol & Nanosci MC2, SE-41296 Gothenburg, Sweden..
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Zhang, Zhi-Bin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Wu, Zhigang
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mechanically Stretchable and Electrically Insulating Thermal Elastomer Composite by Liquid Alloy Droplet Embedment2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 18257Article in journal (Refereed)
    Abstract [en]

    Stretchable electronics and soft robotics have shown unsurpassed features, inheriting remarkable functions from stretchable and soft materials. Electrically conductive and mechanically stretchable materials based on composites have been widely studied for stretchable electronics as electrical conductors using various combinations of materials. However, thermally tunable and stretchable materials, which have high potential in soft and stretchable thermal devices as interface or packaging materials, have not been sufficiently studied. Here, a mechanically stretchable and electrically insulating thermal elastomer composite is demonstrated, which can be easily processed for device fabrication. A liquid alloy is embedded as liquid droplet fillers in an elastomer matrix to achieve softness and stretchability. This new elastomer composite is expected useful to enhance thermal response or efficiency of soft and stretchable thermal devices or systems. The thermal elastomer composites demonstrate advantages such as thermal interface and packaging layers with thermal shrink films in transient and steady-state cases and a stretchable temperature sensor.

  • 191.
    Jeong, Seung Hee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Wu, Zhigang
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tape transfer atomization patterning of liquid alloys for microfluidic stretchable wireless power transfer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 8419-Article in journal (Refereed)
    Abstract [en]

    Stretchable electronics offers unsurpassed mechanical compliance on complex or soft surfaces like the human skin and organs. To fully exploit this great advantage, an autonomous system with a self-powered energy source has been sought for. Here, we present a new technology to pattern liquid alloys on soft substrates, targeting at fabrication of a hybrid-integrated power source in microfluidic stretchable electronics. By atomized spraying of a liquid alloy onto a soft surface with a tape transferred adhesive mask, a universal fabrication process is provided for high quality patterns of liquid conductors in a meter scale. With the developed multilayer fabrication technique, a microfluidic stretchable wireless power transfer device with an integrated LED was demonstrated, which could survive cycling between 0% and 25% strain over 1,000 times.

  • 192.
    Jepson, Paul D.
    et al.
    Zool Soc London, Inst Zool, London NW1 4RY, England..
    Deaville, Rob
    Zool Soc London, Inst Zool, London NW1 4RY, England..
    Barber, Jonathan L.
    Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England..
    Aguilar, Alex
    Univ Barcelona, Dept Anim Biol, Barcelona, Spain.;Univ Barcelona, Biodivers Res Inst IRBio, Barcelona, Spain..
    Borrell, Asuncion
    Univ Barcelona, Dept Anim Biol, Barcelona, Spain.;Univ Barcelona, Biodivers Res Inst IRBio, Barcelona, Spain..
    Murphy, Sinead
    Zool Soc London, Inst Zool, London NW1 4RY, England..
    Barry, Jon
    Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England..
    Brownlow, Andrew
    Scottish Marine Anim Stranding Scheme, SRUC Vet Serv Drummondhill, Inverness IV2 4JZ, Scotland..
    Barnett, James
    Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England..
    Berrow, Simon
    Galway Mayo Inst Technol, Marine & Freshwater Res Ctr, Galway, Ireland..
    Cunningham, Andrew A.
    Zool Soc London, Inst Zool, London NW1 4RY, England..
    Davison, Nicholas J.
    Scottish Marine Anim Stranding Scheme, SRUC Vet Serv Drummondhill, Inverness IV2 4JZ, Scotland..
    ten Doeschate, Mariel
    Scottish Marine Anim Stranding Scheme, SRUC Vet Serv Drummondhill, Inverness IV2 4JZ, Scotland..
    Esteban, Ruth
    CIRCE, Conservat Informat & Res Cetaceans, Algeciras 11390, Spain..
    Ferreira, Marisa
    Univ Minho, Dept Biol, Soc Portuguesa Vida Selvagem, Marine Anim Tissue Bank Portugal, P-4719 Braga, Portugal.;CESAM, Oporto, Portugal..
    Foote, Andrew D.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Genov, Tilen
    Morigenos Slovenian Marine Mammal Soc, Piran 6330, Slovenia.;Univ Primorska, Sci & Res Ctr, Inst Biodivers Studies, Koper, Slovenia.;Univ Primorska, Fac Math Nat Sci & Informat Technol, Dept Biodivers, Koper, Slovenia..
    Gimenez, Joan
    CSIC, EBD, Dept Conservat Biol, Seville 42092, Spain..
    Loveridge, Jan
    Cornwall Wildlife Trust Marine Strandings Network, Truro TR4 9DJ, England..
    Llavona, Angela
    Coordinadora Estudio Mamiferos Marinos CEMMA, Gondomar 36380, Pontevedra, Spain..
    Martin, Vidal
    Soc Estudios Cetaceos Canarias SECAC, Lanzarote, Spain..
    Maxwell, David L.
    Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England..
    Papachlimitzou, Alexandra
    Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England..
    Penrose, Rod
    Marine Environm Monitoring, Cardigan SA43 2PS, Ceredigion, England..
    Perkins, Matthew W.
    Zool Soc London, Inst Zool, London NW1 4RY, England..
    Smith, Brian
    Nat Hist Museum, London SW7 5BD, England..
    de Stephanis, Renaud
    CSIC, EBD, Dept Conservat Biol, Seville 42092, Spain..
    Tregenza, Nick
    Cornwall Wildlife Trust Marine Strandings Network, Truro TR4 9DJ, England..
    Verborgh, Philippe
    CIRCE, Conservat Informat & Res Cetaceans, Algeciras 11390, Spain..
    Fernandez, Antonio
    Univ Las Palmas Gran Canaria, Fac Vet, Gran Canaria, Spain..
    Law, Robin J.
    Zool Soc London, Inst Zool, London NW1 4RY, England.;Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England..
    PCB pollution continues to impact populations of orcas and other dolphins in European waters2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 18573Article in journal (Refereed)
    Abstract [en]

    Organochlorine (OC) pesticides and the more persistent polychlorinated biphenyls (PCBs) have well-established dose-dependent toxicities to birds, fish and mammals in experimental studies, but the actual impact of OC pollutants on European marine top predators remains unknown. Here we show that several cetacean species have very high mean blubber PCB concentrations likely to cause population declines and suppress population recovery. In a large pan-European meta-analysis of stranded (n = 929) or biopsied (n = 152) cetaceans, three out of four species:-striped dolphins (SDs), bottlenose dolphins (BNDs) and killer whales (KWs) had mean PCB levels that markedly exceeded all known marine mammal PCB toxicity thresholds. Some locations (e.g. western Mediterranean Sea, south-west Iberian Peninsula) are global PCB "hotspots" for marine mammals. Blubber PCB concentrations initially declined following a mid-1980s EU ban, but have since stabilised in UK harbour porpoises and SDs in the western Mediterranean Sea. Some small or declining populations of BNDs and KWs in the NE Atlantic were associated with low recruitment, consistent with PCB-induced reproductive toxicity. Despite regulations and mitigation measures to reduce PCB pollution, their biomagnification in marine food webs continues to cause severe impacts among cetacean top predators in European seas.

  • 193. Jiang, Xue
    et al.
    Arhammar, Cecilia
    Liu, Peng
    Zhao, Jijun
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    The R3-carbon allotrope: a pathway towards glassy carbon under high pressure2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 1877-Article in journal (Refereed)
    Abstract [en]

    Pressure-induced bond type switching and phase transformation in glassy carbon (GC) has been simulated by means of Density Functional Theory (DFT) calculations and the Stochastic Quenching method (SQ) in a wide range of pressures (0-79 GPa). Under pressure, the GC experiences a hardening transition from sp-and sp(2)-type to sp(3)-type bonding, in agreement with previous experimental results. Moreover, a new crystalline carbon allotrope possessing R3 symmetry (R3-carbon) is predicted using the stochastic SQ method. The results indicate that R3-carbon can be regarded as an allotrope similar to that of amorphous GC. Avery small difference in the heat of formation and the coherence of the radial and angular distribution functions of GC and the R3-carbon structure imply that small perturbations to this crystalline carbon allotrope may provide another possible amorphization pathway of carbon besides that of quenching the liquid melt or gas by ultra-fast cooling.

  • 194.
    Jingying, Xu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Buck, Moritz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Eklöf, Karin
    Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, SE-75007, Uppsala, Sweden.
    Ahmed Osman, Omneya
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Schaefer, Jeffra K.
    Department of Environmental Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA.
    Bishop, Kevin
    Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Skyllberg, Ulf
    Department of Forest Ecology and Management, Swedish University of Agricultural Science, Umeå, Sweden.
    Björn, Erik
    epartment of Forest Ecology and Management, Swedish University of Agricultural Science, Umeå, Sweden.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Bravo, Andrea Garcia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Department of Marine Biology and Oceanography, Institut de Ciències del Mar, Consejo Superior de Investigaciones Científicas, Barcelona, Catalunya, Spain.
    Mercury methylating microbial communities of boreal forest soils2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 518Article in journal (Refereed)
    Abstract [en]

    The formation of the potent neurotoxic methylmercury (MeHg) is a microbially mediated process that has raised much concern because MeHg poses threats to wildlife and human health. Since boreal forest soils can be a source of MeHg in aquatic networks, it is crucial to understand the biogeochemical processes involved in the formation of this pollutant. High-throughput sequencing of 16S rRNA and the mercury methyltransferase, hgcA, combined with geochemical characterisation of soils, were used to determine the microbial populations contributing to MeHg formation in forest soils across Sweden. The hgcA sequences obtained were distributed among diverse clades, including Proteobacteria, Firmicutes, and Methanomicrobia, with Deltaproteobacteria, particularly Geobacteraceae, dominating the libraries across all soils examined. Our results also suggest that MeHg formation is linked to the composition of also non-mercury methylating bacterial communities, likely providing growth substrate (e.g. acetate) for the hgcA-carrying microorganisms responsible for the actual methylation process. While previous research focused on mercury methylating microbial communities of wetlands, this study provides some first insights into the diversity of mercury methylating microorganisms in boreal forest soils.

  • 195.
    Jirak, Daniel
    et al.
    Inst Clin & Expt Med, Dept Diagnost & Intervent Radiol, MR Unit, Prague 14021, Czech Republic.;Charles Univ Prague, Med Fac 1, Inst Biophys & Informat, Prague, Czech Republic..
    Janacek, Jiri
    Acad Sci Czech Republic, Inst Physiol, Dept Biomath, CR-14220 Prague, Czech Republic..
    Kear, Benjamin P.
    Uppsala University, Music and Museums, Museum of Evolution. Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    A combined MR and CT study for precise quantitative analysis of the avian brain2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16002Article in journal (Refereed)
    Abstract [en]

    Brain size is widely used as a measure of behavioural complexity and sensory-locomotive capacity in avians but has largely relied upon laborious dissections, endoneurocranial tissue displacement, and physical measurement to derive comparative volumes. As an alternative, we present a new precise calculation method based upon coupled magnetic resonance (MR) imaging and computed tomography (CT). Our approach utilizes a novel interactive Fakir probe cross-referenced with an automated CT protocol to efficiently generate total volumes and surface areas of the brain tissue and endoneurocranial space, as well as the discrete cephalic compartments. We also complemented our procedures by using sodium polytungstate (SPT) as a contrast agent. This greatly enhanced CT applications but did not degrade MR quality and is therefore practical for virtual brain tissue reconstructions employing multiple imaging modalities. To demonstrate our technique, we visualized sex-based brain size differentiation in a sample set of Ring-necked pheasants (Phasianus colchicus). This revealed no significant variance in relative volume or surface areas of the primary brain regions. Rather, a trend towards isometric enlargement of the total brain and endoneurocranial space was evidenced in males versus females, thus advocating a non-differential sexually dimorphic pattern of brain size increase amongst these facultatively flying birds.

  • 196. Johansson, Borje
    et al.
    Luo, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Li, Sa
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Cerium; Crystal Structure and Position in The Periodic Table2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 6398-Article in journal (Refereed)
    Abstract [en]

    The properties of the cerium metal have intrigued physicists and chemists for many decades. In particular a lot of attention has been directed towards its high pressure behavior, where an isostructural volume collapse (gamma phase -> alpha phase) has been observed. Two main models of the electronic aspect of this transformation have been proposed; one where the 4f electron undergoes a change from being localized into an itinerant metallic state, and one where the focus is on the interaction between the 4f electron and the conduction electrons, often referred to as the Kondo volume collapse model. However, over the years it has been repeatedly questioned whether the cerium collapse really is isostructural. Most recently, detailed experiments have been able to remove this worrisome uncertainty. Therefore the isostructural aspect of the a-c transition has now to be seriously addressed in the theoretical modeling, something which has been very much neglected. A study of this fundamental characteristic of the cerium volume collapse is made in present paper and we show that the localized reversible arrow delocalized 4f electron picture provides an adequate description of this unique behavior. This agreement makes it possible to suggest that an appropriate crossroad position for cerium in The Periodic Table.

  • 197.
    Johansson, Robert
    et al.
    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.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Hjörvarsson, Björgvin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Scheicher, Ralph H.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Effect of uniaxial strain on the site occupancy of hydrogen in vanadium from density-functional calculations2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10301Article in journal (Refereed)
    Abstract [en]

    We investigate the influence of uniaxial strain on the site occupancy of hydrogen in vanadium, using density functional theory. The site occupancy is found to be strongly influenced by the strain state of the lattice. The results provide the conceptual framework for the atomistic description of the observed hysteresis in the alpha to beta phase transition in bulk, as well as the preferred octahedral occupancy of hydrogen in strained V layers.

  • 198.
    John, R.
    et al.
    Ernst Moritz Arndt Univ Greifswald, Dept Phys, D-17489 Greifswald, Germany..
    Berritta, Marco
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Hinzke, D.
    Univ Konstanz, Dept Phys, D-78457 Constance, Germany..
    Mueller, C.
    Univ Kiel, Inst Mat Sci, D-24143 Kiel, Germany..
    Santos, T.
    Western Digital Corp, San Jose, CA 95131 USA..
    Ulrichs, H.
    Georg August Univ, Phys Inst 1, D-37077 Gottingen, Germany..
    Nieves, P.
    CSIC, Inst Ciencia Mat Madrid, E-28049 Madrid, Spain.;Univ Burgos, Int Res Ctr Crit Raw Mat Adv Ind Technol ICCRAM, Burgos 09001, Spain..
    Walowski, J.
    Ernst Moritz Arndt Univ Greifswald, Dept Phys, D-17489 Greifswald, Germany..
    Mondal, Ritwik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Chubykalo-Fesenko, O.
    CSIC, Inst Ciencia Mat Madrid, E-28049 Madrid, Spain..
    McCord, J.
    Oppeneer, Peter M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Uppsala Univ, Dept Phys & Astron, POB 516, SE-75120 Uppsala, Sweden..
    Nowak, U.
    Univ Konstanz, Dept Phys, D-78457 Constance, Germany..
    Muenzenberg, M.
    Ernst Moritz Arndt Univ Greifswald, Dept Phys, D-17489 Greifswald, Germany..
    Magnetisation switching of FePt nanoparticle recording medium by femtosecond laser pulses2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4114Article in journal (Refereed)
    Abstract [en]

    Manipulation of magnetisation with ultrashort laser pulses is promising for information storage device applications. The dynamics of the magnetisation response depends on the energy transfer from the photons to the spins during the initial laser excitation. A material of special interest for magnetic storage are FePt nanoparticles, for which switching of the magnetisation with optical angular momentum was demonstrated recently. The mechanism remained unclear. Here we investigate experimentally and theoretically the all-optical switching of FePt nanoparticles. We show that the magnetisation switching is a stochastic process. We develop a complete multiscale model which allows us to optimize the number of laser shots needed to switch the magnetisation of high anisotropy FePt nanoparticles in our experiments. We conclude that only angular momentum induced optically by the inverse Faraday effect will provide switching with one single femtosecond laser pulse.

  • 199.
    Jonsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Troll, Valentin R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Högdahl, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Harris, Chris
    Weis, Franz
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Nilsson, Katarina P.
    Skelton, Alasdair
    Magmatic origin of giant 'Kiruna-type' apatite-iron-oxide ores in Central Sweden2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 1644-Article in journal (Refereed)
    Abstract [en]

    Iron is the most important metal for modern industry and Sweden is by far the largest iron-producer in Europe, yet the genesis of Sweden's main iron-source, the 'Kiruna-type' apatite-iron-oxide ores, remains enigmatic. We show that magnetites from the largest central Swedish 'Kiruna-type' deposit at Grangesberg have delta O-18 values between -0.4 and +3.7%, while the 1.90-1.88 Ga meta-volcanic host rocks have d18O values between +4.9 and +9%. Over 90% of the magnetite data are consistent with direct precipitation from intermediate to felsic magmas or magmatic fluids at high-temperature (delta O-18(mgt). > +0.9 parts per thousand, i.e. ortho-magmatic). A smaller group of magnetites (delta O-18(mgt) <= +0.9 parts per thousand), in turn, equilibrated with high-delta O-18, likely meteoric, hydrothermal fluids at low temperatures. The central Swedish 'Kiruna-type' ores thus formed dominantly through magmatic iron-oxide precipitation within a larger volcanic superstructure, while local hydrothermal activity resulted from low-temperature fluid circulation in the shallower parts of this system.

  • 200.
    Josten, Elisabeth
    et al.
    Forschungszentrum Julich, JCNS, D-52425 Julich, Germany.;Forschungszentrum Julich, PGI, JARA FIT, D-52425 Julich, Germany.;Helmholtz Zentrum Dresden Rossendorf, Inst Ion Beam Phys & Mat Res, D-01328 Dresden, Germany..
    Wetterskog, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Glavic, Artur
    Forschungszentrum Julich, JCNS, D-52425 Julich, Germany.;Forschungszentrum Julich, PGI, JARA FIT, D-52425 Julich, Germany.;Paul Scherrer Inst, Lab Neutron Scattering & Imaging, CH-5232 Villigen, Switzerland..
    Boesecke, Peter
    ESRF European Synchrotron, F-38043 Grenoble, France..
    Feoktystov, Artem
    Forschungszentrum Julich, Heinz Maier Leibnitz Zentrum MLZ, JCNS, D-85747 Garching, Germany..
    Brauweiler-Reuters, Elke
    Forschungszentrum Julich, Bioelect ICS 8, Inst Complex Syst, D-52425 Julich, Germany..
    Ruecker, Ulrich
    Forschungszentrum Julich, JCNS, D-52425 Julich, Germany.;Forschungszentrum Julich, PGI, JARA FIT, D-52425 Julich, Germany..
    Salazar-Alvarez, German
    Stockholm Univ, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden..
    Brueckel, Thomas
    Forschungszentrum Julich, JCNS, D-52425 Julich, Germany.;Forschungszentrum Julich, PGI, JARA FIT, D-52425 Julich, Germany..
    Bergstrom, Lennart
    Stockholm Univ, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden..
    Superlattice growth and rearrangement during evaporation-induced nanoparticle self-assembly2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2802Article in journal (Refereed)
    Abstract [en]

    Understanding the assembly of nanoparticles into superlattices with well-defined morphology and structure is technologically important but challenging as it requires novel combinations of in-situ methods with suitable spatial and temporal resolution. In this study, we have followed evaporation-induced assembly during drop casting of superparamagnetic, oleate-capped gamma-Fe2O3 nanospheres dispersed in toluene in real time with Grazing Incidence Small Angle X-ray Scattering (GISAXS) in combination with droplet height measurements and direct observation of the dispersion. The scattering data was evaluated with a novel method that yielded time-dependent information of the relative ratio of ordered (coherent) and disordered particles (incoherent scattering intensities), superlattice tilt angles, lattice constants, and lattice constant distributions. We find that the onset of superlattice growth in the drying drop is associated with the movement of a drying front across the surface of the droplet. We couple the rapid formation of large, highly ordered superlattices to the capillary-induced fluid flow. Further evaporation of interstitital solvent results in a slow contraction of the superlattice. The distribution of lattice parameters and tilt angles was significantly larger for superlattices prepared by fast evaporation compared to slow evaporation of the solvent.

1234567 151 - 200 of 471
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