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

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

  • 2.
    Abreu, Murilo S.
    et al.
    Fed Univ Santa Maria UFSM, Grad Program Pharmacol, BR-97105900 Santa Maria, RS, Brazil.
    Messias, Joao P. M.
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal.
    Thörnqvist, Per-Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Winberg, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Soares, Marta C.
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal.
    Monoaminergic levels at the forebrain and diencephalon signal for the occurrence of mutualistic and conspecific engagement in client reef fish2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7346Article in journal (Refereed)
    Abstract [en]

    Social interactions are commonly found among fish as in mammals and birds. While most animals interact socially with conspecifics some however are also frequently and repeatedly observed to interact with other species (i.e. mutualistic interactions). This is the case of the (so-called) fish clients that seek to be cleaned by other fish (the cleaners). Clients face an interesting challenge: they raise enough motivation to suspend their daily activities as to selectively visit and engage in interactions with cleaners. Here we aimed, for the first time, to investigate the region-specific brain monoaminergic level differences arising from individual client fish when facing a cleaner (interspecific context) compared to those introduced to another conspecific (socio-conspecific context). We show that monoaminergic activity differences occurring at two main brain regions, the diencephalon and the forebrain, are associated with fish clients' social and mutualistic activities. Our results are the first demonstration that monoaminergic mechanisms underlie client fish mutualistic engagement with cleanerfish. These pathways should function as a pre-requisite for cleaning to occur, providing to clients the cognitive and physiological tools to seek to be cleaned.

  • 3.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Musunuri, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6807Article in journal (Refereed)
    Abstract [en]

    The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.

  • 4. Adamik, Peter
    et al.
    Emmenegger, Tamara
    Briedis, Martins
    Gustafsson, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Henshaw, Ian
    Krist, Milos
    Laaksonen, Toni
    Liechti, Felix
    Prochazka, Petr
    Salewski, Volker
    Hahn, Steffen
    Barrier crossing in small avian migrants: individual tracking reveals prolonged nocturnal flights into the day as a common migratory strategy2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21560Article in journal (Refereed)
  • 5.
    Agić, Heda
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology. Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
    Högström, Anette E. S.
    UiT Arctic Univ Norway, Arctic Univ Museum Norway, N-9037 Tromso, Norway.
    Moczydlowska, Malgorzata
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Jensen, Sören
    Univ Extremadura, Area Paleontol, E-06006 Badajoz, Spain.
    Palacios, Teodoro
    Univ Extremadura, Area Paleontol, E-06006 Badajoz, Spain.
    Meinhold, Guido
    Keele Univ, Sch Geog Geol & Environm, Keele ST5 5BG, Staffs, England;Univ Gottingen, Dept Sedimentol & Environm Geol, Goldschmidtstr 3, D-37077 Gottingen, Germany.
    Ebbestad, Jan Ove R.
    Uppsala University, Music and Museums, Museum of Evolution.
    Taylor, Wendy L.
    Univ Cape Town, Dept Geol Sci, ZA-7701 Rondebosch, South Africa.
    Höyberget, Magne
    Rennesveien 14, N-4513 Mandal, Norway.
    Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 14659Article in journal (Refereed)
    Abstract [en]

    Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstatten.

  • 6.
    Ahi, Ehsan Pashay
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Brunel, Mathilde
    Swedish Univ Agr Sci, BioCentrum, Dept Mol Sci, Allmas Alle 5, SE-75007 Uppsala, Sweden.
    Tsakoumis, Emmanouil
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Schmitz, Monika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Transcriptional study of appetite regulating genes in the brain of zebrafish (Danio rerio) with impaired leptin signalling2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 20166Article in journal (Refereed)
    Abstract [en]

    The hormone leptin is a key regulator of body weight, food intake and metabolism. In mammals, leptin acts as an anorexigen and inhibits food intake centrally by affecting the appetite centres in the hypothalamus. In teleost fish, the regulatory connections between leptin and other appetite-regulating genes are largely unknown. In the present study, we used a zebrafish mutant with a loss of function leptin receptor to investigate brain expression patterns of 12 orexigenic and 24 anorexigenic genes under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-hours refeeding). Expression patterns were compared to wild-type zebrafish, in order to identify leptin-dependent differentially expressed genes under different feeding conditions. We provide evidence that the transcription of certain orexigenic and anorexigenic genes is influenced by leptin signalling in the zebrafish brain. We found that the expression of orexigenic genes was not affected by impaired leptin signalling under normal feeding conditions; however, several orexigenic genes showed increased transcription during fasting and refeeding, including agrp, apln, galr1a and cnr1. This suggests an inhibitory effect of leptin signal on the transcription of these orexigenic genes during short-term fasting and refeeding in functional zebrafish. Most pronounced effects were observed in the group of anorexigenic genes, where the impairment of leptin signalling resulted in reduced gene expression in several genes, including cart family, crhb, gnrh2, mc4r, pomc and spx, in the control group. This suggests a stimulatory effect of leptin signal on the transcription of these anorexigenic genes under normal feeding condition. In addition, we found multiple gain and loss in expression correlations between the appetite-regulating genes, in zebrafish with impaired leptin signal, suggesting the presence of gene regulatory networks downstream of leptin signal in zebrafish brain. The results provide the first evidence for the effects of leptin signal on the transcription of various appetite-regulating genes in zebrafish brain, under different feeding conditions. Altogether, these transcriptional changes suggest an anorexigenic role for leptin signal, which is likely to be mediated through distinct set of appetite-regulating genes under different feeding conditions.

  • 7.
    Ahi, Ehsan Pashay
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Karl Franzens Univ Graz, Inst Biol, Univ Pl 2, A-8010 Graz, Austria.
    Richter, Florian
    Karl Franzens Univ Graz, Inst Biol, Univ Pl 2, A-8010 Graz, Austria.
    Lecaudey, Laurene Alicia
    Karl Franzens Univ Graz, Inst Biol, Univ Pl 2, A-8010 Graz, Austria.
    Sefc, Kristina M.
    Karl Franzens Univ Graz, Inst Biol, Univ Pl 2, A-8010 Graz, Austria.
    Gene expression profiling suggests differences in molecular mechanisms of fin elongation between cichlid species2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9052Article in journal (Refereed)
    Abstract [en]

    Comparative analyses of gene regulation inform about the molecular basis of phenotypic trait evolution. Here, we address a fin shape phenotype that evolved multiple times independently across teleost fish, including several species within the family Cichlidae. In a previous study, we proposed a gene regulatory network (GRN) involved in the formation and regeneration of conspicuous filamentous elongations adorning the unpaired fins of the Neolamprologus brichardi. Here, we tested the members of this network in the blockhead cichlid, Steatocranus casuarius, which displays conspicuously elongated dorsal and moderately elongated anal fins. Our study provided evidence for differences in the anatomy of fin elongation and suggested gene regulatory divergence between the two cichlid species. Only a subset of the 20 genes tested in S. casuarius showed the qPCR expression patterns predicted from the GRN identified in N. brichardi, and several of the gene-by-gene expression correlations differed between the two cichlid species. In comparison to N. brichardi, gene expression patterns in S. casuarius were in better (but not full) agreement with gene regulatory interactions inferred in zebrafish. Within S. casuarius, the dorsoventral asymmetry in ornament expression was accompanied by differences in gene expression patterns, including potential regulatory differentiation, between the anal and dorsal fin.

  • 8.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Bonnedahl, Jonas
    Linkoping Univ, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden;Kalmar Cty Hosp, Dept Infect Dis, SE-39185 Kalmar, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden.
    Hernandez, Jorge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7361Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

  • 9.
    Alam, Syed Bahauddin
    et al.
    Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
    Almutairi, Bader
    Missouri S&T, Dept Nucl Engn, Rolla, MO USA.
    Ridwan, Tuhfatur
    Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
    Kumar, Dinesh
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Goodwin, Cameron S.
    Rhode Isl Nucl Sci Ctr, 16 Reactor Rd, Narragansett, RI 02882 USA.
    Atkinson, Kirk D.
    Univ Ontario Inst Technol, 2000 Simcoe St North, Oshawa, ON L1G 0C5, Canada.
    Parks, Geoffrey T.
    Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
    Neutronic investigation of alternative & composite burnable poisons for the soluble-boron-free and long life civil marine small modular reactor cores2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 19591Article in journal (Refereed)
    Abstract [en]

    Concerns about the effects of global warming provide a strong case to consider how best nuclear power could be applied to marine propulsion. Currently, there are persistent efforts worldwide to combat global warming, and that also includes the commercial freight shipping sector. In an effort to decarbonize the marine sector, there are growing interests in replacing the contemporary, traditional propulsion systems with nuclear propulsion systems. The latter system allows freight ships to have longer intervals before refueling; subsequently, lower fuel costs, and minimal carbon emissions. Nonetheless, nuclear propulsion systems have remained largely confined to military vessels. It is highly desirable that a civil marine core not use soluble boron for reactivity control, but it is then a challenge to achieve an adequate shutdown margin throughout the core life while maintaining reactivity control and acceptable power distributions in the core. High-thickness ZrB2 150 mu m Integral Fuel Burnable Absorber (IFBA) is an excellent burnable poison (BP) candidate for long life soluble-boron-free core. However, in this study, we want to minimize the use of 150 mu m IFBA since B-10 undergoes an (n, alpha) capture reaction, and the resulting helium raises the pressure within the plenum and in the cladding. Therefore, we have considered several alternative and novel burnable BP design strategies to minimize the use of IFBA for reactivity control in this study: (Case 1) a composite BP: gadolinia (Gd2O3) or erbia (Er2O3) with 150 mu m thickness ZrB2 IFBA; (Case 2) Pu-240 or Am-241 mixed homogeneously with the fuel; and (Case 3) another composite BP: Pu-240 or Am-241 with 150 mu m thickness ZrB2 IFBA. The results are compared against those for a high-thickness 150 mu m 25 IFBA pins design from a previous study. The high-thickness 150 mu m 25 IFBA pins design is termed the "IFBA-only" BP design throughout this study. We arrive at a design using 15% U-235 fuel loaded into 13 x 13 assemblies with Case 3 BPs (IFBA+Pu-240 or IFBA+Am-241) for reactivity control while reducing 20% IFBA use. This design exhibits lower assembly reactivity swing and minimal burnup penalty due to the self-shielding effect. Case 3 provides similar to 10% more initial (beginning-of-life) reactivity suppression with similar to 70% less reactivity swing compared to the IFBA-only design for UO2 fuel while achieving almost the same core lifetime. Finally, optimized Case 3 assemblies were loaded in 3D nodal diffusion and reactor model code. The results obtained from the 3D reactor model confirmed that the designed core with the proposed Case 3 BPs can achieve the target lifetime of 15 years while contributing to similar to 10% higher BOL reactivity suppression, similar to 70% lower reactivity swings, similar to 30% lower radial form factor and similar to 28% lower total peaking factor compared to the IFBA-only core.

  • 10.
    Alatalo, Juha M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Little, Chelsea J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Jagerbrand, Annika K.
    Molau, Ulf
    Vascular plant abundance and diversity in an alpine heath under observed and simulated global change2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10197Article in journal (Refereed)
    Abstract [en]

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

  • 11.
    Alavian-Ghavanini, Ali
    et al.
    Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden;Karolinska Inst, Dept Clin Neurosci, CMM, S-17164 Solna, Sweden.
    Lin, Ping-I
    Karlstad Univ, Dept Hlth Sci, S-65188 Karlstad, Sweden.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rimfors, Sabina Risen
    Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Tang, Mandy
    Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden.
    Lindh, Christian
    Lund Univ, Div Occupat & Environm Med, S-22185 Lund, Sweden.
    Bornehag, Carl-Gustaf
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA;Karlstad Univ, Dept Hlth Sci, S-65188 Karlstad, Sweden.
    Rueegg, Joelle
    Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden;Karolinska Inst, Dept Clin Neurosci, CMM, S-17164 Solna, Sweden.
    Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11315Article in journal (Refereed)
    Abstract [en]

    Bisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, Iow APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and Iow APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.

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

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

  • 13.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA.;King Abdulaziz Univ, Dept Phys, Rabigh 21911, Saudi Arabia..
    Andersson, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    DNA intercalation optimized by two-step molecular lock mechanism2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37993Article in journal (Refereed)
    Abstract [en]

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

  • 14.
    Ameur, Adam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Meiring, Tracy L.
    Bunikis, Ignas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Häggqvist, Susana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindau, Cecilia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lindberg, Julia Hedlund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustavsson, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mbulawa, Zizipho Z. A.
    Williamson, Anna-Lise
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 4398-Article in journal (Refereed)
    Abstract [en]

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

  • 15.
    Amlinger, Lina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Hoekzema, Mirthe
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Wagner, Gerhart E. H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Koskiniemi, Sanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Lundgren, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Fluorescent CRISPR Adaptation Reporter for rapid quantification of spacer acquisition2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10392Article in journal (Refereed)
    Abstract [en]

    CRISPR-Cas systems are adaptive prokaryotic immune systems protecting against horizontally transferred DNA or RNA such as viruses and other mobile genetic elements. Memory of past invaders is stored as spacers in CRISPR loci in a process called adaptation. Here we developed a novel assay where spacer integration results in fluorescence, enabling detection of memory formation in single cells and quantification of as few as 0.05% cells with expanded CRISPR arrays in a bacterial population. Using this fluorescent CRISPR Adaptation Reporter (f-CAR), we quantified adaptation of the two CRISPR arrays of the type I-E CRISPR-Cas system in Escherichia coli, and confirmed that more integration events are targeted to CRISPR-II than to CRISPR-I. The f-CAR conveniently analyzes and compares many samples, allowing new insights into adaptation. For instance, we show that in an E. coli culture the majority of acquisition events occur in late exponential phase.

  • 16.
    Andersson, J.
    et al.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Zagorodskikh, Sergey
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden;.
    Roos, A. Hult
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Talaee, O.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden;Univ Oulu, Nano & Mol Syst Res Unit, POB 3000, FI-90014 Oulu, Finland.
    Squibb, R. J.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Koulentianos, D.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden;Sorbonne Univ, Lab Chim Phys Matiere & Rayonnement, CNRS, F-75005 Paris 05, France.
    Wallner, M.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Zhaunerchyk, V
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Singh, R.
    Weizmann Inst Sci, Dept Particle Phys & Astrophys, IL-7610001 Rehovot, Israel.
    Eland, J. H. D.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden;Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, South Parks Rd, Oxford OX1 3QZ, England.
    Rost, J. M.
    Max Planck Inst Phys Komplexer Syst, Nothnitzer Str 38, D-01187 Dresden, Germany.
    Feifel, R.
    Univ Gothenburg, Dept Phys, Origovagen 6B, S-41296 Gothenburg, Sweden.
    Parametrization of energy sharing distributions in direct double photoionization of He2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 17883Article in journal (Refereed)
    Abstract [en]

    We present experimental results on the characteristic sharing of available excess energy, ranging from 11-221 eV, between two electrons in single-photon direct double ionization of He. An effective parametrization of the sharing distributions is presented along with an empirical model that describes the complete shape of the distribution based on a single experimentally determinable parameter. The measured total energy sharing distributions are separated into two distributions representing the shake-off and knock-out parts by simulating the sharing distribution curves expected from a pure wave collapse after a sudden removal of the primary electron. In this way, empirical knock-out distributions are extracted and both the shake-off and knock-out distributions are parametrized. These results suggest a simple method that can be applied to other atomic and molecular systems to experimentally study important aspects of the direct double ionization process.

  • 17.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

  • 18.
    Andersson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Almqvist, Bjarne S. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Burchardt, Steffi
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Troll, Valentin R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Malehmir, Alireza
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Snowball, Ian
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Natural Resources and Sustainable Development.
    Kubler, Lutz
    Geol Survey Sweden, Uppsala, Sweden..
    Magma transport in sheet intrusions of the Alnö carbonatite complex, central Sweden2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 27635Article in journal (Refereed)
    Abstract [en]

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

  • 19.
    Andersson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Malehmir, Alireza
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Troll, Valentin R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Solid Earth Geology.
    Dehghannejad, Mahdieh
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Juhlin, Christopher
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Ask, Maria
    Carbonatite ring-complexes explained by caldera-style volcanism2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 1677-Article in journal (Refereed)
    Abstract [en]

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

  • 20.
    Andersson, Mikael S.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Pappas, Spyridon D.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Stopfel, Henry
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Östman, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Stein, A.
    Brookhaven Natl Lab, Ctr Funct Nanomat, POB 5000, Upton, NY 11973 USA..
    Nordblad, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Mathieu, Roland
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Hjörvarsson, Björgvin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Kapaklis, Vassilios
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Thermally induced magnetic relaxation in square artificial spin ice2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37097Article in journal (Refereed)
    Abstract [en]

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

  • 21.
    Aqvist, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kamerlin, Shina C. Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15817Article in journal (Refereed)
    Abstract [en]

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

  • 22.
    Araujo, Carlos Moyses
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Nagar, Sandeep
    Ramzan, Muhammad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Shukla, R.
    Jayakumar, O. D.
    Tyagi, A. K.
    Liu, Yi-Sheng
    Chen, Jeng-Lung
    Glans, Per-Anders
    Chang, Chinglin
    Blomqvist, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Lizárraga, Raquel
    Holmstrom, Erik
    Belova, Lyubov
    Guo, Jinghua
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Applied Materials Physics, Department of Materials and Engineering, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.
    Rao, K. V.
    Disorder-induced Room Temperature Ferromagnetism in Glassy Chromites2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 4686-Article in journal (Refereed)
    Abstract [en]

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

  • 23.
    Arffman, R. K.
    et al.
    Univ Oulu, Oulu Univ Hosp, Med Res Ctr, Dept Obstet & Gynecol,PEDEGO Res Unit, Oulu, Finland.
    Saraswat, M.
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland.
    Joenväärä, S.
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland.
    Khatun, M.
    Univ Oulu, Oulu Univ Hosp, Med Res Ctr, Dept Obstet & Gynecol,PEDEGO Res Unit, Oulu, Finland.
    Agarwal, R.
    All India Inst Med Sci, Dept Reprod Biol, New Delhi 110029, India.
    Tohmola, T.
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Renkonen, R.
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland.
    Piltonen, T. T.
    Univ Oulu, Oulu Univ Hosp, Med Res Ctr, Dept Obstet & Gynecol,PEDEGO Res Unit, Oulu, Finland.
    Thromboinflammatory changes in plasma proteome of pregnant women with PCOS detected by quantitative label-free proteomics2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 17578Article in journal (Refereed)
    Abstract [en]

    Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. Several adverse pregnancy outcomes and abnormalities of the placenta have been associated with PCOS. By using quantitative label-free proteomics we investigated whether changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. A total of 169 proteins with >= 2 unique peptides were detected to be differentially expressed between women with PCOS (n = 7) and matched controls (n = 20) at term of pregnancy, out of which 35 were significant (p-value < 0.05). A pathway analysis revealed that networks related to humoral immune responses, inflammatory responses, cardiovascular disease and cellular growth and proliferation were affected by PCOS. Classification of cases and controls was carried out using principal component analysis, orthogonal projections on latent structure-discriminant analysis (OPLS-DA), hierarchical clustering, self-organising maps and ROC-curve analysis. The most significantly enriched proteins in PCOS were properdin and insulin-like growth factor II. In the dataset, properdin had the best predictive accuracy for PCOS (AUC=1). Additionally, properdin abundances correlated with AMH levels in pregnant women.

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

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

  • 25.
    Asp, Michaela
    et al.
    KTH Royal Inst Technol, Div Gene Technol, Sci Life Lab, Stockholm, Sweden..
    Salmen, Fredrik
    KTH Royal Inst Technol, Div Gene Technol, Sci Life Lab, Stockholm, Sweden..
    Ståhl, Patrik L.
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Vickovic, Sanja
    KTH Royal Inst Technol, Div Gene Technol, Sci Life Lab, Stockholm, Sweden..
    Felldin, Ulrika
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Löfling, Marie
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Navarro, Jose Fernandez
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Maaskola, Jonas
    KTH Royal Inst Technol, Div Gene Technol, Sci Life Lab, Stockholm, Sweden..
    Eriksson, Maria J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Persson, Bengt
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Corbascio, Matthias
    Karolinska Univ Hosp, Dept Cardiothorac Surg & Anesthesiol, Solna, Sweden..
    Persson, Hans
    Danderyd Hosp, Dept Cardiol, Stockholm, Sweden.;Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Linde, Cecilia
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Lundeberg, Joakim
    KTH Royal Inst Technol, Div Gene Technol, Sci Life Lab, Stockholm, Sweden..
    Spatial detection of fetal marker genes expressed at low level in adult human heart tissue2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12941Article in journal (Refereed)
    Abstract [en]

    Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.

  • 26.
    Atabaki-Pasdar, Naeimeh
    et al.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Ohlsson, Mattias
    Lund Univ, Dept Astron & Theoret Phys, Computat Biol & Biol Phys Unit, Lund, Sweden..
    Shungin, Dmitry
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Kurbasic, Azra
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Pearson, Ewan R.
    Univ Dundee, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Ali, Ashfaq
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Statistical power considerations in genotype-based recall randomized controlled trials2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37307Article in journal (Refereed)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

  • 27.
    Attermeyer, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Leibniz Inst Freshwater Ecol & Inland Fisheries C, Muggelseedamm 310, D-12587 Berlin, Germany..
    Flury, S.
    Leibniz Inst Freshwater Ecol & Inland Fisheries C, Muggelseedamm 310, D-12587 Berlin, Germany.;Univ Geneva, Fac Sci, Blvd Carl Vogt 66, CH-1211 Geneva, Switzerland..
    Jayakumar, R.
    IITM, IGCS, Madras 600036, Tamil Nadu, India.;IITM, Environm & Water Resources Engn Div, Dept Civil Engn, Madras 600036, Tamil Nadu, India..
    Fiener, P.
    Univ Augsburg, Dept Geog, Alter Postweg 118, D-86159 Augsburg, Germany..
    Steger, K.
    IITM, IGCS, Madras 600036, Tamil Nadu, India..
    Arya, V.
    IITM, Environm & Water Resources Engn Div, Dept Civil Engn, Madras 600036, Tamil Nadu, India..
    Wilken, F.
    Univ Augsburg, Dept Geog, Alter Postweg 118, D-86159 Augsburg, Germany.;BTU, Chair Soil Protect & Recultivat, Konrad Wachsmann Allee 6, D-03013 Cottbus, Germany..
    van Geldern, R.
    Univ Erlangen Nurnberg, GeoZentrum Nordbayern, Schlossgarten 5, D-91054 Erlangen, Germany..
    Premke, K.
    Leibniz Inst Freshwater Ecol & Inland Fisheries C, Muggelseedamm 310, D-12587 Berlin, Germany.;Leibniz Ctr Agr Landscape Res ZALF, Inst Landscape Biogeochem, Eberswalder Str 84, D-15374 Muncheberg, Germany..
    Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20424Article in journal (Refereed)
    Abstract [en]

    Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km(2)) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets.

  • 28.
    Attwood, Misty M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Krishnan, Arunkumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12387Article in journal (Refereed)
    Abstract [en]

    The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.

  • 29.
    Autieri, Carmine
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Kumar, P. Anil
    Univ Duisburg Essen, Fac Phys Duisburg Essen CeNIDE, D-47057 Duisburg, Germany..
    Walecki, Dirk
    Univ Duisburg Essen, Fac Phys Duisburg Essen CeNIDE, D-47057 Duisburg, Germany..
    Webers, Samira
    Univ Duisburg Essen, Fac Phys Duisburg Essen CeNIDE, D-47057 Duisburg, Germany..
    Gubbins, Mark A.
    Seagate Technol, 1 Disc Dr, Springtown BT48 0BF, North Ireland..
    Wende, Heiko
    Univ Duisburg Essen, Fac Phys Duisburg Essen CeNIDE, D-47057 Duisburg, Germany..
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Recipe for High Moment Materials with Rare-earth and 3d Transition Metal Composites2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 29307Article in journal (Refereed)
    Abstract [en]

    Materials with high volume magnetization are perpetually needed for the generation of sufficiently large magnetic fields by writer pole of magnetic hard disks, especially for achieving increased areal density in storage media. In search of suitable materials combinations for this purpose, we have employed density functional theory to predict the magnetic coupling between iron and gadolinium layers separated by one to several monolayers of 3d transition metals (Sc-Zn). We demonstrate that it is possible to find ferromagnetic coupling for many of them and in particular for the early transition metals giving rise to high moment. Cr and Mn are the only elements able to produce a significant ferromagnetic coupling for thicker spacer layers. We also present experimental results on two trilayer systems Fe/Sc/Gd and Fe/Mn/Gd. From the experiments, we confirm a ferromagnetic coupling between Fe and Gd across a 3 monolayers Sc spacer or a Mn spacer thicker than 1 monolayer. In addition, we observe a peculiar dependence of Fe/Gd magnetic coupling on the Mn spacer thickness.

  • 30.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Eckerdal, Patricia
    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.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    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.
    Investigating the association between neuroticism and adverse obstetric and neonatal outcomes2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15470Article in journal (Refereed)
    Abstract [en]

    Neuroticism is not only associated with affective disorders but also with certain somatic health problems. However, studies assessing whether neuroticism is associated with adverse obstetric or neonatal outcomes are scarce. This observational study comprises first-time mothers (n = 1969) with singleton pregnancies from several cohorts based in Uppsala, Sweden. To assess neuroticism-related personality, the Swedish universities Scales of Personality was used. Swedish national health registers were used to extract outcomes and confounders. In logistic regression models, odds ratios (ORs) with 95% confidence intervals (Cis) were calculated for the outcomes by an increase of 63 units of neuroticism (equalling the interquartile range). Analyses were adjusted for maternal age, educational level, height, body mass index, year of delivery, smoking during pregnancy, involuntary childlessness, and psychiatric morbidity. Main outcomes were mode of delivery, gestational diabetes mellitus, gestational hypertension, preeclampsia, induction of delivery, prolonged delivery, severe lacerations, placental retention, postpartum haemorrhage, premature birth, infant born small or large for gestational age, and Apgar score. Neuroticism was not independently associated with adverse obstetric or neonatal outcomes besides gestational diabetes. For future studies, models examining sub-components of neuroticism or pregnancy-specific anxiety are encouraged.

  • 31.
    Backman, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Falk Delgado, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Cupisti, Kenko
    Marien Hosp, Dept Surg, Euskirchen, Germany..
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 44943Article in journal (Refereed)
    Abstract [en]

    Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.

  • 32.
    Backman, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
    Cupisti, Kenko
    Marien Hosp, Dept Surg, Euskirchen, Germany.
    Willenberg, Holger S.
    Rostock Univ, Med Ctr, Div Endocrinol & Metab, Rostock, Germany.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6269Article in journal (Refereed)
    Abstract [en]

    Aldosterone producing adenomas (APAs) occur in the adrenal glands of around 30% of patients with primary aldosteronism, the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1 have been described in similar to 60% of these tumours. We subjected 15 aldosterone producing adenomas (13 with known mutations and two without) to RNA Sequencing and Whole Genome Sequencing (n = 2). All known mutations were detected in the RNA-Seq reads, and mutations in ATP2B3 (G123R) and CACNA1D (S410L) were discovered in the tumours without known mutations. Adenomas with CTNNB1 mutations showed a large number of differentially expressed genes (1360 compared to 106 and 75 for KCNJ5 and ATP1A1/ATP2B3 respectively) and clustered together in a hierarchical clustering analysis. RT-PCR in an extended cohort of 49 APAs confirmed higher expression of AFF3 and ISM1 in APAs with CTNNB1 mutations. Investigation of the expression of genes involved in proliferation and apoptosis revealed subtle differences between tumours with and without CTNNB1 mutations. Together our results consolidate the notion that CTNNB1 mutations characterize a distinct subgroup of APAs.

  • 33. Bagger-Sjoback, Dan
    et al.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Tideholm, Bo
    Johansson, Ann
    Hellstrom, Sten
    Hakizimana, Pierre
    Fridberger, Anders
    High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 13341Article in journal (Refereed)
    Abstract [en]

    Otosclerosis is a common disorder that leads to conductive hearing loss. Most patients with otosclerosis also have tinnitus, and surgical treatment is known to improve hearing as well as tinnitus. Some patients however experience worsening of tinnitus after the operation, but there are no known factors that allow surgeons to predict who will be at risk. In this prospective observational study on 133 patients undergoing stapedotomy, we show that postoperative air conduction thresholds at very high stimulus frequencies predict improvement of tinnitus, as assessed with proportional odds logistic regression models. Young patients were significantly more likely to experience reduction of tinnitus and patients whose tinnitus became better were also more satisfied with the outcome of the operation. These findings have practical importance for patients and their surgeons. Young patients can be advised that surgery is likely to be beneficial for their tinnitus, but a less positive message should be conveyed to older patients.

  • 34.
    Bass, Tarek Z.
    et al.
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Mitran, Bogdan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Frejd, Fredrik Y.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Affibody AB, SE-17163 Solna, Sweden.
    Löfblom, John
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Ståhl, Stefan
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43118Article in journal (Refereed)
    Abstract [en]

    Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with In-111 via a DOTA chelator. The residence time of In-111-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. In-111-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, In-111-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct In-111-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of In-111-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours.

  • 35.
    Behra, Phani Rama Krishna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Das, Sarbashis
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Pettersson, B. M. Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Shirreff, Lisa
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    DuCote, Tanner
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    Jacobsson, Karl-Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ennis, Don G.
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    Kirsebom, Leif A
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Extended insight into the Mycobacterium chelonae-abscessus complex through whole genome sequencing of Mycobacterium salmoniphilum outbreak and Mycobacterium salmoniphilum-like strains2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4603Article in journal (Refereed)
    Abstract [en]

    Members of the Mycobacterium chelonae-abscessus complex (MCAC) are close to the mycobacterial ancestor and includes both human, animal and fish pathogens. We present the genomes of 14 members of this complex: the complete genomes of Mycobacterium salmoniphilum and Mycobacterium chelonae type strains, seven M. salmoniphilum isolates, and five M. salmoniphilum-like strains including strains isolated during an outbreak in an animal facility at Uppsala University. Average nucleotide identity (ANI) analysis and core gene phylogeny revealed that the M. salmoniphilum-like strains are variants of the human pathogen Mycobacterium franklinii and phylogenetically close to Mycobacterium abscessus. Our data further suggested that M. salmoniphilum separates into three branches named group I, II and III with the M. salmoniphilum type strain belonging to group II. Among predicted virulence factors, the presence of phospholipase C (plcC), which is a major virulence factor that makes M. abscessus highly cytotoxic to mouse macrophages, and that M. franklinii originally was isolated from infected humans make it plausible that the outbreak in the animal facility was caused by a M. salmoniphilum-like strain. Interestingly, M. salmoniphilum-like was isolated from tap water suggesting that it can be present in the environment. Moreover, we predicted the presence of mutational hotspots in the M. salmoniphilum isolates and 26% of these hotspots overlap with genes categorized as having roles in virulence, disease and defense. We also provide data about key genes involved in transcription and translation such as sigma factor, ribosomal protein and tRNA genes.

  • 36.
    Behra, Phani Rama Krishna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Pettersson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Ramesh, Malavika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Dasgupta, Santanu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Kirsebom, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Insight into the biology of Mycobacterium mucogenicum and Mycobacterium neoaurum Glade members2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 19259Article in journal (Refereed)
    Abstract [en]

    Nontuberculous mycobacteria, NTM, are of growing concern and among these members of the Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clades can cause infections in humans and they are resistant to first-line anti-tuberculosis drugs. They can be isolated from different ecological niches such as soil, tap water and ground water. Mycobacteria, such as Mmuc and Mneo, are classified as rapid growing mycobacteria, RGM, while the most familiar, Mycobacterium tuberculosis, belongs to the slow growing mycobacteria, SGM. Modern "omics" approaches have provided new insights into our understanding of the biology and evolution of this group of bacteria. Here we present comparative genomics data for seventeen NTM of which sixteen belong to the Mmuc- and Mneo-clades. Focusing on virulence genes, including genes encoding sigma/anti-sigma factors, serine threonine protein kinases (STPK), type VII (ESX genes) secretion systems and mammalian cell entry (Mce) factors we provide insight into their presence as well as phylogenetic relationship in the case of the sigma/anti-sigma factors and STPKs. Our data further suggest that these NTM lack ESX-5 and Mce2 genes, which are known to affect virulence. In this context, Mmuc- and Mneo-clade members lack several of the genes in the glycopeptidolipid (GLP) locus, which have roles in colony morphotype appearance and virulence. For the M. mucogenicum type strain, Mmuc(T), we provide RNASeq data focusing on mRNA levels for sigma factors, STPK, ESX proteins and Mce proteins. These data are discussed and compared to in particular the SGM and fish pathogen Mycobacterium marinum. Finally, we provide insight into as to why members of the Mmuc- and Mneo-clades show resistance to rifampin and isoniazid, and why Mmuc(T) forms a rough colony morphotype.

  • 37.
    Bekaert, J.
    et al.
    Univ Antwerp, Dept Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
    Bignardi, L.
    Univ Groningen, Zernike Inst Adv Mat, Nijenborgh 4, NL-9747 AG Groningen, Netherlands.; Elettra Sincrotrone Trieste, Str Statale 14 Km 163-5, I-34149 Trieste, Italy.
    Aperis, Alex
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    van Abswoude, P.
    Univ Groningen, Zernike Inst Adv Mat, Nijenborgh 4, NL-9747 AG Groningen, Netherlands.
    Mattevi, C.
    IOM CNR, Lab TASC, Str Statale 14 Km 163-5, I-34149 Trieste, Italy.; Imperial Coll London, Dept Mat, Exhibit Rd, London SW7 2AZ, England.
    Gorovikov, S.
    Elettra Sincrotrone Trieste, Str Statale 14 Km 163-5, I-34149 Trieste, Italy.; Canadian Light Source Inc, 44 Innovat Blvd, Saskatoon, SK S7N 2V3, Canada.
    Petaccia, L.
    Elettra Sincrotrone Trieste, Str Statale 14 Km 163-5, I-34149 Trieste, Italy.
    Goldoni, A.
    Elettra Sincrotrone Trieste, Str Statale 14 Km 163-5, I-34149 Trieste, Italy.
    Partoens, B.
    Univ Antwerp, Dept Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
    Oppeneer, Peter M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Peeters, F. M.
    Univ Antwerp, Dept Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
    Milošević, M. V.
    Univ Antwerp, Dept Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
    Rudolf, P.
    Univ Groningen, Zernike Inst Adv Mat, Nijenborgh 4, NL-9747 AG Groningen, Netherlands.
    Cepek, C.
    IOM CNR, Lab TASC, Str Statale 14 Km 163-5, I-34149 Trieste, Italy .
    Free surfaces recast superconductivity in few-monolayer MgB2: Combined first-principles and ARPES demonstration2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 14458Article in journal (Refereed)
    Abstract [en]

    Two-dimensional materials are known to harbour properties very different from those of their bulk counterparts. Recent years have seen the rise of atomically thin superconductors, with a caveat that superconductivity is strongly depleted unless enhanced by specific substrates, intercalants or adatoms. Surprisingly, the role in superconductivity of electronic states originating from simple free surfaces of two-dimensional materials has remained elusive to date. Here, based on first-principles calculations, anisotropic Eliashberg theory, and angle-resolved photoemission spectroscopy (ARPES), we show that surface states in few-monolayer MgB2 make a major contribution to the superconducting gap spectrum and density of states, clearly distinct from the widely known, bulk-like σ- and π-gaps. As a proof of principle, we predict and measure the gap opening on the magnesium-based surface band up to a critical temperature as high as ~30 K for merely six monolayers thick MgB2. These findings establish free surfaces as an unavoidable ingredient in understanding and further tailoring of superconductivity in atomically thin materials.

  • 38.
    Belonoshko, Anatoly B.
    et al.
    Condensed Matter Theory, Department of Theoretical Physics, AlbaNova University Center, KTH Royal Institute of Technology, SE- 106 91 Stockholm, Sweden.
    Ramzan, Muhammad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Mao, Ho-kwang
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Applied Materials Physics, Department of Materials and Engineering, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.
    Atomic Diffusion in Solid Molecular Hydrogen2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2340-Article in journal (Refereed)
    Abstract [en]

    We performed ab initio molecular dynamics simulations of the C2c and Cmca-12 phases of hydrogen at pressures from 210 to 350 GPa. These phases were predicted to be stable at 0 K and pressures above 200 GPa. However, systematic studies of temperature impact on properties of these phases have not been performed so far. Filling this gap, we observed that on temperature increase diffusion sets in the Cmca-12 phase, being absent in C2c. We explored the mechanism of diffusion and computed melting curve of hydrogen at extreme pressures. The results suggest that the recent experiments claiming conductive hydrogen at the pressure around 260 GPa and ambient temperature might be explained by the diffusion. The diffusion might also be the reason for the difference in Raman spectra obtained in recent experiments.

  • 39.
    Berggren, Peter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Fransson, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Electron Paramagnetic Resonance of Single Magnetic Moment on a Surface2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25584Article in journal (Refereed)
    Abstract [en]

    We address electron spin resonance of single magnetic moments in a tunnel junction using time-dependent electric fields and spin-polarized current. We show that the tunneling current directly depends on the local magnetic moment and that the frequency of the external electric field mixes with the characteristic Larmor frequency of the local spin. The importance of the spin-polarized current induced anisotropy fields acting on the local spin moment is, moreover, demonstrated. Our proposed model thus explains the absence of an electron spin resonance for a half integer spin, in contrast with the strong signal observed for an integer spin.

  • 40.
    Bergman, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Hellsvik, Johan
    KTH Royal Inst Technol, Sch Informat & Commun Technol, Dept Mat & Nano Phys, Electrum 229, SE-16440 Kista, Sweden..
    Bessarab, Pavel F.
    KTH Royal Inst Technol, Sch Informat & Commun Technol, Dept Mat & Nano Phys, Electrum 229, SE-16440 Kista, Sweden.;Univ Iceland, Inst Sci, VR 3, IS-107 Reykjavik, Iceland..
    Delin, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Sch Informat & Commun Technol, Dept Mat & Nano Phys, Electrum 229, SE-16440 Kista, Sweden.;KTH Royal Inst Technol, Swedish E Sci Res Ctr SeRC, SE-10044 Stockholm, Sweden..
    Spin relaxation signature of colossal magnetic anisotropy in platinum atomic chains2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36872Article in journal (Refereed)
    Abstract [en]

    Recent experimental data demonstrate emerging magnetic order in platinum atomically thin nanowires. Furthermore, an unusual form of magnetic anisotropy-colossal magnetic anisotropy (CMA)-was earlier predicted to exist in atomically thin platinum nanowires. Using spin dynamics simulations based on first-principles calculations, we here explore the spin dynamics of atomically thin platinum wires to reveal the spin relaxation signature of colossal magnetic anisotropy, comparing it with other types of anisotropy such as uniaxial magnetic anisotropy (UMA). We find that the CMA alters the spin relaxation process distinctly and, most importantly, causes a large speed-up of the magnetic relaxation compared to uniaxial magnetic anisotropy. The magnetic behavior of the nanowire exhibiting CMA should be possible to identify experimentally at the nanosecond time scale for temperatures below 5 K. This time-scale is accessible in e.g., soft x-ray free electron laser experiments.

  • 41.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Åhlén, Emma
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Holst, Bodil Ström
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Characterization of canine anti-mouse antibodies highlights that multiple strategies are needed to combat immunoassay interference2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 14521Article in journal (Refereed)
    Abstract [en]

    Immunoassays are widely used for detection and quantification of analytes in biological samples, but are vulnerable to analytical errors caused by interfering sample substances. Of particular interest are endogenous anti-animal antibodies that may bind to the immunoassay antibodies and cause erroneous test results. This phenomenon is a hazard to patient safety in both human and veterinary medicine. Here, we demonstrate that anti-mouse antibodies in dogs bind selectively to different regions of the murine IgG molecule, cross-react with IgG from different species, and consist of all major antibody classes present in canine serum (IgA, IgG and IgM). The antibody characteristics varied among individuals and their prevalence differed between two dog breeds. The selective binding to different IgG regions suggests that the antibodies might not originate from immunization through exposure to mice or other species. These findings show that canine anti-mouse antibodies are highly heterogeneous in nature and therefore require a combination of strategies to be counteracted.

  • 42.
    Bessarab, Pavel F.
    et al.
    Univ Iceland, Sci Inst, IS-107 Reykjavik, Iceland.;ITMO Univ, St Petersburg 197101, Russia..
    Müller, Gideon P.
    Univ Iceland, Sci Inst, IS-107 Reykjavik, Iceland.;Forschungszentrum Julich, Peter Grunberg Inst, D-52425 Julich, Germany.;Forschungszentrum Julich, Inst Adv Simulat, D-52425 Julich, Germany.;JARA, D-52425 Julich, Germany..
    Lobanov, Igor S.
    ITMO Univ, St Petersburg 197101, Russia..
    Rybakov, Filipp N.
    KTH Royal Inst Technol, Dept Phys, SE-10691 Stockholm, Sweden..
    Kiselev, Nikolai S.
    Forschungszentrum Julich, Peter Grunberg Inst, D-52425 Julich, Germany.;Forschungszentrum Julich, Inst Adv Simulat, D-52425 Julich, Germany.;JARA, D-52425 Julich, Germany..
    Jonsson, Hannes
    Univ Iceland, Sci Inst, IS-107 Reykjavik, Iceland.;Aalto Univ, FI-00076 Espoo, Finland..
    Uzdin, Valery M.
    ITMO Univ, St Petersburg 197101, Russia.;St Petersburg State Univ, Dept Phys, St Petersburg 198504, Russia.;ITMO Univ, St Petersburg 197101, Russia..
    Blügel, Stefan
    Forschungszentrum Julich, Peter Grunberg Inst, D-52425 Julich, Germany.;Forschungszentrum Julich, Inst Adv Simulat, D-52425 Julich, Germany.;JARA, D-52425 Julich, Germany..
    Bergqvist, Lars
    KTH Royal Inst Technol, Sch Engn Sci, Dept Appl Phys, Electrum 229, SE-16440 Kista, Sweden.;KTH Royal Inst Technol, SeRC Swedish E Sci Res Ctr, SE-10044 Stockholm, Sweden..
    Delin, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Sch Engn Sci, Dept Appl Phys, Electrum 229, SE-16440 Kista, Sweden.;KTH Royal Inst Technol, SeRC Swedish E Sci Res Ctr, SE-10044 Stockholm, Sweden..
    Lifetime of racetrack skyrmions2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3433Article in journal (Refereed)
    Abstract [en]

    The skyrmion racetrack is a promising concept for future information technology. There, binary bits are carried by nanoscale spin swirls-skyrmions-driven along magnetic strips. Stability of the skyrmions is a critical issue for realising this technology. Here we demonstrate that the racetrack skyrmion lifetime can be calculated from first principles as a function of temperature, magnetic field and track width. Our method combines harmonic transition state theory extended to include Goldstone modes, with an atomistic spin Hamiltonian parametrized from density functional theory calculations. We demonstrate that two annihilation mechanisms contribute to the skyrmion stability: At low external magnetic field, escape through the track boundary prevails, but a crossover field exists, above which the collapse in the interior becomes dominant. Considering a Pd/Fe bilayer on an Ir(111) substrate as a well-established model system, the calculated skyrmion lifetime is found to be consistent with reported experimental measurements. Our simulations also show that the Arrhenius pre-exponential factor of escape depends only weakly on the external magnetic field, whereas the pre-exponential factor for collapse is strongly field dependent. Our results open the door for predictive simulations, free from empirical parameters, to aid the design of skyrmion-based information technology.

  • 43. Bezerra-Neto, Manoel M.
    et al.
    Ribeiro, Marcelo S.
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Bergman, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Muniz, Roberto B.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Klautau, Angela B.
    Complex magnetic structure of clusters and chains of Ni and Fe on Pt(111)2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 3054-Article in journal (Refereed)
    Abstract [en]

    We present an approach to control the magnetic structure of adatoms adsorbed on a substrate having a high magnetic susceptibility. Using finite Ni-Pt and Fe-Pt nanowires and nanostructures on Pt(111) surfaces, our ab initio results show that it is possible to tune the exchange interaction and magnetic configuration of magnetic adatoms (Fe or Ni) by introducing different numbers of Pt atoms to link them, or by including edge effects. The exchange interaction between Ni (or Fe) adatoms on Pt(111) can be considerably increased by introducing Pt chains to link them. The magnetic ordering can be regulated allowing for ferromagnetic or antiferromagnetic configurations. Noncollinear magnetic alignments can also be stabilized by changing the number of Pt-mediated atoms. An Fe-Pt triangularly-shaped nanostructure adsorbed on Pt(111) shows the most complex magnetic structure of the systems considered here: a spin-spiral type of magnetic order that changes its propagation direction at the triangle vertices.

  • 44.
    Bhandary, Sumanta
    et al.
    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.
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Defect controlled magnetism in FeP/graphene/Ni(111)2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 3405-Article in journal (Refereed)
    Abstract [en]

    Spin switching of organometallic complexes by ferromagnetic surfaces is an important topic in the area of molecular nanospintronics. Moreover, graphene has been shown as a 2D surface for physisorption of molecular magnets and strain engineering on graphene can tune the spin state of an iron porphyrin (FeP) molecule from S = 1 to S = 2. Our ab initio density functional calculations suggest that a pristine graphene layer placed between a Ni(111) surface and FeP yields an extremely weak exchange interaction between FeP and Ni whereas the introduction of defects in graphene shows a variety of ferromagnetic and antiferromagnetic exchange interactions. Moreover, these defects control the easy axes of magnetization, strengths of magnetic anisotropy energies and spin-dipolar contributions. Our study suggests a new way of manipulating molecular magnetism by defects in graphene and hence has the potential to be explored in designing spin qubits to realize logic operations in molecular nanospintronics.

  • 45.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Psychology, University of Southern Denmark, Odense, Denmark;Department of Psychology, Lund University, Lund, Sweden.
    Schiller, Daniela
    Li, Jian
    Davidson, Per
    Rosén, Jörgen
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Mårtensson, Johan
    Kirk, Ulrich
    The effect of mindfulness training on extinction retention2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 19896Article in journal (Refereed)
    Abstract [en]

    Anxiety and trauma related disorders are highly prevalent, causing suffering and high costs for society. Current treatment strategies, although effective, only show moderate effect-sizes when compared to adequate control groups demonstrating a need to develop new forms of treatment or optimize existing ones. In order to achieve this, an increased understanding of what mechanisms are involved is needed. An emerging literature indicates that mindfulness training (MFT) can be used to treat fear and anxiety related disorders, but the treatment mechanisms are unclear. One hypothesis, largely based on findings from neuroimaging studies, states that MFT may improve extinction retention, but this has not been demonstrated empirically. To investigate this question healthy subjects either completed a 4-week MFT- intervention delivered through a smart-phone app (n = 14) or were assigned to a waitlist (n = 15). Subsequently, subjects participated in a two-day experimental protocol using pavlovian aversive conditioning, evaluating acquisition and extinction of threat-related responses on day 1, and extinction retention on day 2. Results showed that the MFT group displayed reduced spontaneous recovery of threat related arousal responses, as compared to the waitlist control group, on day 2. MFT did not however, have an effect on either the acquisition or extinction of conditioned responses day 1. This clarifies the positive effect of MFT on emotional functioning and could have implications for the treatment of anxiety and trauma related disorders.

  • 46.
    Boeckel, Jes-Niels
    et al.
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany;German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, Frankfurt, Germany;Univ Hosp Leipzig, Dept Internal Med, Cardiol, Leipzig, Germany.
    Palapies, Lars
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany.
    Klotsche, Jens
    Tech Univ Dresden, Clin Psychol & Psychotherapy, Dresden, Germany.
    Zeller, Tanja
    German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
    von Jeinsen, Beatrice
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany;German Ctr Cardiovasc Dis DZHK, Berlin, Germany.
    Perret, Maya F.
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany.
    Kleinhaus, Soeren L.
    Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, Frankfurt, Germany.
    Pieper, Lars
    Tech Univ Dresden, Clin Psychol & Psychotherapy, Dresden, Germany.
    Tzikas, Stergios
    Aristotle Univ Thessaloniki, Ippokrateio Hosp, Dept Cardiol 3, Thessaloniki, Greece;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 2, Mainz, Germany.
    Leistner, David
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany;German Ctr Cardiovasc Dis DZHK, Berlin, Germany.
    Bickel, Christoph
    Fed Armed Forces Hosp, Dept Internal Med, Koblenz, Germany.
    Stalla, Guenter K.
    Max Planck Inst Psychiat, Neuroendocrinol, Munich, Germany.
    Lehnert, Hendrik
    Univ Hosp Schleswig Holstein, Dept Internal Med 1, Lubeck, Germany.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wittchen, Hans-Ulrich
    Tech Univ Dresden, Clin Psychol & Psychotherapy, Dresden, Germany.
    Silber, Sigmund
    Praxisklin, Kardiol Gemeinschaftspraxis, Munich, Germany.
    Baldus, Stephan
    Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany;Univ Cologne, Heart Ctr, Cologne, Germany.
    Maerz, Winfried
    Synlab Serv GmbH, Synlab Akad Arztl Fortbildung, Mannheim, Germany.
    Dimmeler, Stefanie
    German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, Frankfurt, Germany.
    Blankenberg, Stefan
    German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
    Muenzel, Thomas
    German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 2, Mainz, Germany.
    Zeiher, Andreas M.
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany;German Ctr Cardiovasc Dis DZHK, Berlin, Germany.
    Keller, Till
    Goethe Univ Frankfurt, Univ Hosp, Dept Internal Med 3, Cardiol, Frankfurt, Germany;German Ctr Cardiovasc Dis DZHK, Berlin, Germany;Kerckhoff Heart & Thorax Ctr, Bad Nauheim, Germany.
    Adjusted Troponin I for Improved Evaluation of Patients with Chest Pain2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8087Article in journal (Refereed)
    Abstract [en]

    The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with r(age) = 0.436/0.518 and with (r)(eGFR) = -0.142/-0.207. For adjustment, these variables served as covariates in a linear regression model with cTnl as dependent variable. This adjustment model was then applied to a real-world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients.

  • 47.
    Bolund, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Lummaa, Virpi
    Univ Turku, Dept Biol, FIN-20014 Turku, Finland.;Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England..
    Smith, Ken R.
    Univ Utah, Huntsman Canc Inst, Dept Family & Consumer Studies & Populat Sci, Salt Lake City, UT 84112 USA..
    Hanson, Heidi A.
    Univ Utah, Huntsman Canc Inst, Dept Family & Prevent Med & Populat Sci, Salt Lake City, UT 84112 USA..
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 24672Article in journal (Refereed)
    Abstract [en]

    The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution.

  • 48.
    Bongoni, Anjan K.
    et al.
    St Vincents Hosp Melbourne, Immunol Res Ctr, Fitzroy, Vic, Australia..
    Salvaris, Evelyn
    St Vincents Hosp Melbourne, Immunol Res Ctr, Fitzroy, Vic, Australia..
    Nordling, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Klymiuk, Nikolai
    Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Munich, Germany..
    Wolf, Eckhard
    Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Munich, Germany..
    Ayares, David L.
    Revivicor Inc, Blacksburg, VA USA..
    Rieben, Robert
    Univ Bern, Dept Clin Res, Bern, Switzerland..
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cowan, Peter J.
    St Vincents Hosp Melbourne, Immunol Res Ctr, Fitzroy, Vic, Australia.;Univ Melbourne, Dept Med, Melbourne, Vic, Australia..
    Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4450Article in journal (Refereed)
    Abstract [en]

    Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno) transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (GTKO. hCD46. hTBM) pig aortic endothelial cells (PAEC) in two pig-to-human in vitro xenotransplantation settings. Model 1: incubation of untreated or hTNFa-treated PAEC with 10% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation activation in WT and GTKO. hCD46. hTBM PAEC. Coating of untreated or hTNFa-treated PAEC with CHC (100 mu g/ml) protected against human plasma-induced endothelial activation and damage. Model 2: PAEC were grown on microcarrier beads, coated with CHC, and incubated with non-anticoagulated whole human blood. Genetically modified PAEC significantly prolonged clotting time of human blood (115.0 +/- 16.1 min, p < 0.001) compared to WT PAEC (34.0 +/- 8.2 min). Surface CHC significantly improved the human blood compatibility of PAEC, as shown by increased clotting time (WT: 84.3 +/- 11.3 min, p < 0.001; GTKO. hCD46. hTBM: 146.2 +/- 20.4 min, p < 0.05) and reduced platelet adhesion, complement activation, coagulation activation and inhibition of fibrinolysis. The combination of CHC coating and genetic modification provided the greatest compatibility with human blood, suggesting that pre-transplant perfusion of genetically modified porcine organs with CHC may benefit post-transplant xenograft function.

  • 49.
    Bovornratanaraks, Thiti
    et al.
    Chulalongkorn Univ, Fac Sci, Dept Phys, ECPRL, Bangkok, Thailand; Chulalongkorn Univ, Fac Sci, Dept Phys, PEMRU, Bangkok, Thailand; Commiss Higher Educ, Thailand Ctr Excellence Phys, Bangkok, Thailand.
    Tsuppayakorn-aek, Prutthipong
    Chulalongkorn Univ, Fac Sci, Dept Phys, ECPRL, Bangkok, Thailand; Chulalongkorn Univ, Fac Sci, Dept Phys, PEMRU, Bangkok, Thailand; Commiss Higher Educ, Thailand Ctr Excellence Phys, Bangkok, Thailand.
    Luo, Wei
    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, Technology, Department of Engineering Sciences, Solid State Physics. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol KTH, Appl Mat Phys, Dept Mat & Engn, Stockholm, Sweden.
    Ground-state structure of semiconducting and superconducting phases in xenon carbides at high pressure2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2459Article in journal (Refereed)
    Abstract [en]

    The 'missing Xe paradox' is one of the phenomena at the Earth's atmosphere. Studying the 'missing Xe paradox' will provide insights into a chemical reaction of Xe with C. We search the ground-state structure candidates of xenon carbides using the Universal Structure Predictor: Evolutionary Xtallography (USPEX) code, which has been successfully applied to a variety of systems. We predict that XeC2 is the most stable among the convex hull. We find that the I((4) over bar)2m structure of XeC2 is the semiconducting phase. Accurate electronic structures of tetragonal XeC2 have been calculated using a hybrid density functionals HSE06, which gives larger more accurate band gap than a GGA-PBE exchange-correlation functional. Specifically, we find that the I((4) over bar)2m structure of XeC2 is a dynamically stable structure at high pressure. We also predict that the P6/mmm structure of XeC2 is the superconducting phase with a critical temperature of 38 K at 200 GPa. The ground-state structure of xenon carbides is of critical importance for understanding in the missing Xe. We discuss the inference of the stable structures of XeC2. The accumulation of electrons between Xe and C led to the stability by investigating electron localization function (ELF).

  • 50.
    Brandis, Gerrit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hughes, Diarmaid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mechanisms of fitness cost reduction for rifampicin-resistant strains with deletion or duplication mutations in rpoB.2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17488Article in journal (Refereed)
    Abstract [en]

    Rifampicin resistance (Rif(R)) is caused by mutations in rpoB, encoding the beta-subunit of RNA polymerase. Rif(R )mutations generally incur a fitness cost and in resistant isolates are frequently accompanied by compensatory mutations in rpoA, rpoB or rpoC. Previous studies of fitness compensation focused on Rif(R) caused by amino acid substitutions within rpoB. Rif(R) is also caused by deletion and duplication mutations in rpoB but it is not known whether or how such mutants can ameliorate their fitness costs. Using experimental evolution of Salmonella carrying Rif(R) deletion or duplication mutations we identified compensatory amino acid substitution mutations within rpoA, rpoB or rpoC in 16 of 21 evolved lineages. Additionally, we found one lineage where a large deletion was compensated by duplication of adjacent amino acids (possibly to fill the gap within the protein structure), two lineages where mutations occurred outside of rpoABC, and two lineages where a duplication mutant reverted to the wild-type sequence. All but the two revertant mutants maintained the Rif(R) phenotype. These data suggest that amino acid substitution mutations are the major compensatory mechanism regardless of the nature of the primary Rif(R) mutation.

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