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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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, 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 apoptosis2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 1575Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Winberg, Svante
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    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 fish2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 7346Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Musunuri, Sravani
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 6807Artikel i tidskrift (Refereegranskat)
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Zooekologi.
    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 strategy2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 21560Artikel i tidskrift (Refereegranskat)
  • 5.
    Agić, Heda
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Paleobiologi. 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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Paleobiologi.
    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 universitet, Enheten för musik och museer, Evolutionsmuseet.
    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 Norway2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 14659Artikel i tidskrift (Refereegranskat)
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi. 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 species2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 9052Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Olsen, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    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 analysis2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 7361Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Alatalo, Juha M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Little, Chelsea J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Jagerbrand, Annika K.
    Molau, Ulf
    Vascular plant abundance and diversity in an alpine heath under observed and simulated global change2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 10197Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rimfors, Sabina Risen
    Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden.
    Lejonklou, Margareta Halin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    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 Humans2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 11315Artikel i tidskrift (Refereegranskat)
    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.

  • 10. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 13312Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - 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 mechanism2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 37993Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Ameur, Adam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Meiring, Tracy L.
    Bunikis, Ignas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Häggqvist, Susana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindau, Cecilia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lindberg, Julia Hedlund
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gustavsson, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mbulawa, Zizipho Z. A.
    Williamson, Anna-Lise
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing2014Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, s. 4398-Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Amlinger, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hoekzema, Mirthe
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Wagner, Gerhart E. H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Koskiniemi, Sanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Fluorescent CRISPR Adaptation Reporter for rapid quantification of spacer acquisition2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 10392Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Amlinger, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hoekzema, Mirthe
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Wagner, Gerhart E. H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Koskiniemi, Sanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Fluorescent CRISPR Adaptation Reporter for rapid quantification of spacer acquisition2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 10392Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Andersson, Jonathan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lundström, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Engström, Mathias
    GE Healthcare.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Medical.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Medical.
    Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 12358Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Andersson, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Almqvist, Bjarne S. G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Burchardt, Steffi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Mineralogi, petrologi och tektonik.
    Troll, Valentin R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Mineralogi, petrologi och tektonik.
    Malehmir, Alireza
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Snowball, Ian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Naturresurser och hållbar utveckling.
    Kubler, Lutz
    Geol Survey Sweden, Uppsala, Sweden..
    Magma transport in sheet intrusions of the Alnö carbonatite complex, central Sweden2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 27635Artikel i tidskrift (Refereegranskat)
    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.

  • 17.
    Andersson, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Malehmir, Alireza
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Troll, Valentin R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Berggrundsgeologi.
    Dehghannejad, Mahdieh
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Juhlin, Christopher
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Geofysik.
    Ask, Maria
    Carbonatite ring-complexes explained by caldera-style volcanism2013Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, s. 1677-Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Andersson, Mikael S.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Pappas, Spyridon D.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Stopfel, Henry
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Östman, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Stein, A.
    Brookhaven Natl Lab, Ctr Funct Nanomat, POB 5000, Upton, NY 11973 USA..
    Nordblad, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Mathieu, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Hjörvarsson, Björgvin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Kapaklis, Vassilios
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Thermally induced magnetic relaxation in square artificial spin ice2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 37097Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Aqvist, Johan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kamerlin, Shina C. Lynn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Struktur- och molekylärbiologi.
    Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 15817Artikel i tidskrift (Refereegranskat)
    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.

  • 20.
    Araujo, Carlos Moyses
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Nagar, Sandeep
    Ramzan, Muhammad
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Shukla, R.
    Jayakumar, O. D.
    Tyagi, A. K.
    Liu, Yi-Sheng
    Chen, Jeng-Lung
    Glans, Per-Anders
    Chang, Chinglin
    Blomqvist, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Lizárraga, Raquel
    Holmstrom, Erik
    Belova, Lyubov
    Guo, Jinghua
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. 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 Chromites2014Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, s. 4686-Artikel i tidskrift (Refereegranskat)
    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.

  • 21. 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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Panigrahi, Puspamitra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Trukhan, Vladimir M.
    Chatterji, Tapan
    Marenkin, Sergey F.
    Shoukavaya, Tatyana V.
    Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic chalcopyrites2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, s. 7720-Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    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 universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. 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 tissue2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 12941Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    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 trials2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 37307Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    Attermeyer, Katrin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. 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 lake2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 20424Artikel i tidskrift (Refereegranskat)
    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.

  • 25.
    Attwood, Misty M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Krishnan, Arunkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sällman Almén, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 12387Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Autieri, Carmine
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Recipe for High Moment Materials with Rare-earth and 3d Transition Metal Composites2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 29307Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Backman, Samuel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Maharjan, Rajani
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Falk Delgado, Alberto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Cupisti, Kenko
    Marien Hosp, Dept Surg, Euskirchen, Germany..
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 44943Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Backman, Samuel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Åkerström, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Maharjan, Rajani
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 6269Artikel i tidskrift (Refereegranskat)
    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.

  • 29. Bagger-Sjoback, Dan
    et al.
    Strömbäck, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lillieström, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Tideholm, Bo
    Johansson, Ann
    Hellstrom, Sten
    Hakizimana, Pierre
    Fridberger, Anders
    High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 13341Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Bass, Tarek Z.
    et al.
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Rosestedt, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Frejd, Fredrik Y.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Affibody AB, SE-17163 Solna, Sweden.
    Löfblom, John
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Ståhl, Stefan
    KTH Royal Inst Technol, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 43118Artikel i tidskrift (Refereegranskat)
    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.

  • 31.
    Behra, Phani Rama Krishna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Das, Sarbashis
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Pettersson, B. M. Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Shirreff, Lisa
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    DuCote, Tanner
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    Jacobsson, Karl-Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Ennis, Don G.
    Univ Louisiana, Dept Biol, Lafayette, LA USA.
    Kirsebom, Leif A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Extended insight into the Mycobacterium chelonae-abscessus complex through whole genome sequencing of Mycobacterium salmoniphilum outbreak and Mycobacterium salmoniphilum-like strains2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 4603Artikel i tidskrift (Refereegranskat)
    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.

  • 32.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    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 demonstration2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, nr 1, artikel-id 14458Artikel i tidskrift (Refereegranskat)
    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.

  • 33.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Mao, Ho-kwang
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. Applied Materials Physics, Department of Materials and Engineering, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.
    Atomic Diffusion in Solid Molecular Hydrogen2013Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, s. 2340-Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Berggren, Peter
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Fransson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Electron Paramagnetic Resonance of Single Magnetic Moment on a Surface2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 25584Artikel i tidskrift (Refereegranskat)
    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.

  • 35.
    Bergman, Anders
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. 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 chains2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 36872Artikel i tidskrift (Refereegranskat)
    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.

  • 36.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    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 interference2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, nr 1, artikel-id 14521Artikel i tidskrift (Refereegranskat)
    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.

  • 37.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. 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 skyrmions2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 3433Artikel i tidskrift (Refereegranskat)
    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.

  • 38. Bezerra-Neto, Manoel M.
    et al.
    Ribeiro, Marcelo S.
    Sanyal, Biplab
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Bergman, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Muniz, Roberto B.
    Eriksson, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Klautau, Angela B.
    Complex magnetic structure of clusters and chains of Ni and Fe on Pt(111)2013Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, s. 3054-Artikel i tidskrift (Refereegranskat)
    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.

  • 39.
    Bhandary, Sumanta
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Eriksson, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Sanyal, Biplab
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Defect controlled magnetism in FeP/graphene/Ni(111)2013Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, s. 3405-Artikel i tidskrift (Refereegranskat)
    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.

  • 40.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    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 Pain2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 8087Artikel i tidskrift (Refereegranskat)
    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.

  • 41.
    Bolund, Elisabeth
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Zooekologi.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Zooekologi.
    Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 24672Artikel i tidskrift (Refereegranskat)
    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.

  • 42.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    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 blood2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 4450Artikel i tidskrift (Refereegranskat)
    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.

  • 43.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. 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 pressure2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 2459Artikel i tidskrift (Refereegranskat)
    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).

  • 44.
    Brandis, Gerrit
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hughes, Diarmaid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mechanisms of fitness cost reduction for rifampicin-resistant strains with deletion or duplication mutations in rpoB.2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 17488Artikel i tidskrift (Refereegranskat)
    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.

  • 45.
    Breinl, Korbinian
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Luft-, vatten och landskapslära.
    Di Baldassarre, Giuliano
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Luft-, vatten och landskapslära.
    Girons Lopez, Marc
    Department of Geography, University of Zurich.
    Hagenlocher, Michael
    Institute for Environment and Human Security, United Nations University (UNU-EHS).
    Vico, Giulia
    Department of Crop Production Ecology, Swedish University of Agricultural Sciences.
    Rutgersson, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Luft-, vatten och landskapslära.
    Can weather generation capture precipitation patterns across different climates, spatial scales and under data scarcity?2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 5449Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stochastic weather generators can generate very long time series of weather patterns, which are indispensable in earth sciences, ecology and climate research. Yet, both their potential and limitations remain largely unclear because past research has typically focused on eclectic case studies at small spatial scales in temperate climates. In addition, stochastic multi-site algorithms are usually not publicly available, making the reproducibility of results difficult. To overcome these limitations, we investigated the performance of the reduced-complexity multi-site precipitation generator TripleM across three different climatic regions in the United States. By resampling observations, we investigated for the first time the performance of a multi-site precipitation generator as a function of the extent of the gauge network and the network density. The definition of the role of the network density provides new insights into the applicability in data-poor contexts. The performance was assessed using nine different statistical metrics with main focus on the inter-annual variability of precipitation and the lengths of dry and wet spells. Among our study regions, our results indicate a more accurate performance in wet temperate climates compared to drier climates. Performance deficits are more marked at larger spatial scales due to the increasing heterogeneity of climatic conditions.

  • 46.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Landegren, Nils
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Stockholm, Sweden..
    Sjöberg, Ronald
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, SE-17121 Solna, Sweden..
    Hallgren, Åsa
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden..
    Renneker, Stefanie
    Euroimmun AG, D-23560 Lubeck, Germany..
    Lattwein, Erik
    Euroimmun AG, D-23560 Lubeck, Germany..
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, SE-17121 Solna, Sweden..
    Andersson, Goran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Lilliehöök, Inger
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst Harvard & MIT, Cambridge, USA..
    Kämpe, Olle
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden.; Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.;Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, N-5021 Bergen, Norway.;Haukeland Hosp, Dept Med, N-5021 Bergen, Norway..
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 4852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.

  • 47.
    Broeckx, Bart J. G.
    et al.
    Univ Ghent, Lab Anim Genet, Fac Vet Med, Merelbeke, Belgium..
    Derrien, Thomas
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Mottier, Stephanie
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Wucher, Valentin
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Cadieu, Edouard
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Hedan, Benoit
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Le Beguec, Celine
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Botherel, Nadine
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA USA.
    Saunders, Jimmy H.
    Univ Ghent, Dept Med Imaging & Orthoped, Fac Vet Med, Merelbeke, Belgium..
    Deforce, Dieter
    Univ Ghent, Fac Pharmaceut Sci, Lab Pharmaceut Biotechnol, Ghent, Belgium..
    Andre, Catherine
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    Peelman, Luc
    Univ Ghent, Lab Anim Genet, Fac Vet Med, Merelbeke, Belgium..
    Hitte, Christophe
    Univ Rennes 1, CNRS URM6290, Inst Genet & Dev Rennes, Rennes, France..
    An exome sequencing based approach for genome-wide association studies in the dog2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 15680Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) are widely used to identify loci associated with phenotypic traits in the domestic dog that has emerged as a model for Mendelian and complex traits. However, a disadvantage of GWAS is that it always requires subsequent fine-mapping or sequencing to pinpoint causal mutations. Here, we performed whole exome sequencing (WES) and canine high-density (cHD) SNP genotyping of 28 dogs from 3 breeds to compare the SNP and linkage disequilibrium characteristics together with the power and mapping precision of exome-guided GWAS (EG-GWAS) versus cHD-based GWAS. Using simulated phenotypes, we showed that EG-GWAS has a higher power than cHD to detect associations within target regions and less power outside target regions, with power being influenced further by sample size and SNP density. We analyzed two real phenotypes (hair length and furnishing), that are fixed in certain breeds to characterize mapping precision of the known causal mutations. EG-GWAS identified the associated exonic and 3'UTR variants within the FGF5 and RSPO2 genes, respectively, with only a few samples per breed. In conclusion, we demonstrated that EG-GWAS can identify loci associated with Mendelian phenotypes both within and across breeds.

  • 48. Broeckx, Bart J. G.
    et al.
    Hitte, Christophe
    Coopman, Frank
    Verhoeven, Geert E. C.
    De Keulenaer, Sarah
    De Meester, Ellen
    Derrien, Thomas
    Alfoldi, Jessica
    Lindblad-Toh, Kerstin
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Bosmans, Tim
    Gielen, Ingrid
    Van Bree, Henri
    Van Ryssen, Bernadette
    Saunders, Jimmy H.
    Van Nieuwerburgh, Filip
    Deforce, Dieter
    Improved canine exome designs, featuring ncRNAs and increased coverage of protein coding genes2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 12810Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    By limiting sequencing to those sequences transcribed as mRNA, whole exome sequencing is a cost-efficient technique often used in disease-association studies. We developed two target enrichment designs based on the recently released annotation of the canine genome: the exome-plus design and the exome-CDS design. The exome-plus design combines the exons of the CanFam 3.1 Ensembl annotation, more recently discovered protein-coding exons and a variety of non-coding RNA regions (microRNAs, long non-coding RNAs and antisense transcripts), leading to a total size of approximate to 152 Mb. The exome-CDS was designed as a subset of the exome-plus by omitting all 3' and 5' untranslated regions. This reduced the size of the exome-CDS to approximate to 71 Mb. To test the capturing performance, four exome-plus captures were sequenced on a NextSeq 500 with each capture containing four pre-capture pooled, barcoded samples. At an average sequencing depth of 68.3x, 80% of the regions and well over 90% of the targeted base pairs were completely covered at least 5 times with high reproducibility. Based on the performance of the exome-plus, we estimated the performance of the exome-CDS. Overall, these designs provide flexible solutions for a variety of research questions and are likely to be reliable tools in disease studies.

  • 49.
    Browning, Kathryn L.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lind, T. K.
    Malmo Univ, Dept Biomed Sci & Biofilms, Malmo, Sweden..
    Maric, S.
    Malmo Univ, Dept Biomed Sci & Biofilms, Malmo, Sweden..
    Malekkhaiat Häffner, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Fredrikson, G. N.
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Bengtsson, E.
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Univ Copenhagen, Dept Pharm, Copenhagen, Denmark..
    Cardenas, M.
    Malmo Univ, Dept Biomed Sci & Biofilms, Malmo, Sweden..
    Human Lipoproteins at Model Cell Membranes: Effect of Lipoprotein Class on Lipid Exchange2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 7478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid exchange and lipid removal can be distinguished thanks to the combined use of hydrogenated and tail-deuterated lipids. Both HDL and LDL remove lipids from the bilayer and deposit hydrogenated material into the lipid bilayer, however, the extent of removal and exchange depends on LP type. These results support the notion of HDL acting as the 'good' cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the 'bad' cholesterol, depositing lipid material into the vascular wall.

  • 50.
    Bränn, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Rostedt Punga, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartumIngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Artikel i tidskrift (Refereegranskat)
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