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  • 251.
    Nordell, Erik
    et al.
    Linköpings universitet, Biogas Research Center. Tekniska Verken Linkoping AB Publ, Dept Biogas RandD, SE-58115 Linkoping, Sweden .
    B Hansson, Anna
    Linköpings universitet, Biogas Research Center. Tekniska Verken Linkoping AB Publ, Dept Biogas RandD, SE-58115 Linkoping, Sweden .
    Karlsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Biogas Research Center. Tekniska Verken Linkoping AB Publ, Dept Biogas RandD, SE-58115 Linkoping, Sweden .
    Zeolites relieves inhibitory stress from high concentrations of long chain fatty acids2013Inngår i: Waste Management, ISSN 0956-053X, E-ISSN 1879-2456, Vol. 33, nr 12, s. 2659-2663Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein and fat rich slaughterhouse waste is a very attractive waste stream for the production of biogas because of the high biochemical methane potential of the substrate. The material has however some drawbacks as the sole material for biogas production due to the production of several process disturbing metabolites such as ammonia, sulfides and long chain fatty acids. We can in this work present results that show that zeolites have the potential to relieve inhibitory stress from the presence of long chain fatty acids. Moreover, the results strongly indicate that it is mainly acetic acid consumers that are most negatively affected by long chain fatty acids and that the mechanism of stress relief is an adsorption of long chain fatty acids to the zeolites. In addition to this, it is shown that the effect is immediate and that only a small amount of zeolites is necessary to cancel the inhibitory effect of long chain fatty acids.

  • 252.
    Nordeman, Patrik
    et al.
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
    Johansson, Leif B. G.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Bäck, Marcus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Estrada, Sergio
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden..
    Hall, Håkan
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden..
    Sjölander, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Westermark, Gunilla T.
    Department of Medicinal Cell Biology, Uppsala University, Uppsala, Sweden.
    Westermark, Per
    Department of Immunology, Genetics and Pathology, Uppsala University, UppsalaSweden.
    Nilsson, Lars
    Department of Pharmacology, University of Oslo, Oslo, Norway.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, K. Peter R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Antoni, Gunnar
    Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
    11C and 18FRadiolabeling of Tetra- and Pentathiophenes as PET-ligands for Amyloid Protein Aggregates2016Inngår i: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, nr 4, s. 368-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Three oligothiophenes were evaluated as PET tracers for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver and spleen. To verify the specificity of the oligothiophenes towards amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, in vivo rat and monkey PET-CT studies showed very low uptake in the brain, pancreas and heart of the healthy animals indicating low non-specific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.

  • 253.
    Novotny, Renata
    et al.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Langer, Franziska
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Mahler, Jasmin
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Skodras, Angelos
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Vlachos, Andreas
    Goethe University of Frankfurt, Germany.
    Wegenast-Braun, Bettina M.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Kaeser, Stephan A.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Neher, Jonas J.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Eisele, Yvonne S.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Pietrowski, Marie J.
    University of Freiburg, Germany.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Deller, Thomas
    Goethe University of Frankfurt, Germany.
    Staufenbiel, Matthias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Heimrich, Bernd
    University of Freiburg, Germany.
    Jucker, Mathias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Conversion of Synthetic A beta to In Vivo Active Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model2016Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 36, nr 18, s. 5084-5093Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aggregation of amyloid-beta peptide (A beta) inbrain is an early event and hallmark of Alzheimers disease (AD). We combined the advantages of in vitro and in vivo approaches to study cerebral beta-amyloidosis by establishing a long-term hippocampal slice culture(HSC) model. While no A beta deposition was noted in untreated HSCs of postnatal A beta precursor protein transgenic (APP tg) mice, A beta deposition emerged in HSCs when cultures were treated once with brain extract from aged APP tg mice and the culture medium was continuously supplemented with synthetic A beta. Seeded A beta deposition was also observed under the same conditions in HSCs derived from wild-type or App-null mice but in no comparable way when HSCs were fixed before cultivation. Both the nature of the brain extract and the synthetic A beta species determined the conformational characteristics of HSCA beta deposition. HSCA beta deposits induced a microglia response, spine loss, and neuritic dystrophy but no obvious neuron loss. Remarkably, in contrast to in vitro aggregated synthetic A beta, homogenates of A beta deposits containing HSCs induced cerebral beta-amyloidosis upon intracerebral inoculation into young APP tg mice. Our results demonstrate that a living cellular environment promotes the seeded conversion of synthetic A beta into a potent in vivo seeding-active form.

  • 254.
    Nugraha, Roni
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Finlay, John A.
    University of Birmingham, England.
    Hill, Sophie
    University of Birmingham, England.
    Fyrner, Timmy
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Yandi, Wetra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Callow, Maureen E.
    University of Birmingham, England.
    Callow, James A.
    University of Birmingham, England.
    Ederth, Thomas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Antifouling properties of oligo(lactose)-based self-assembled monolayers2015Inngår i: Biofouling (Print), ISSN 0892-7014, E-ISSN 1029-2454, Vol. 31, nr 1, s. 123-134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The antifouling (AF) properties of oligo(lactose)-based self-assembled monolayers (SAMs), using four different proteins, zoospores of the green alga Ulva linza and cells of the diatom Navicula incerta, were investigated. The SAM-forming alkylthiols, which contained 1, 2 or 3 lactose units, showed significant variation in AF properties, with no differences in wettability. Non-specific adsorption of albumin and pepsin was low on all surfaces. Adsorption of lysozyme and fibrinogen decreased with increasing number of lactose units in the SAM, in agreement with the generally observed phenomenon that thicker hydrated layers provide higher barriers to protein adsorption. Settlement of spores of U. linza followed an opposite trend, being greater on the bulkier, more hydrated SAMs. These SAMs are more ordered for the larger saccharide units, and it is therefore hypothesized that the degree of order, and differences in crystallinity or stiffness between the surfaces, is an important parameter regulating spore settlement on these surfaces.

  • 255.
    Nystrom, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nelson, Erin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Reitan, Nina
    Norwegian University of Science and Technology.
    Ellingsen, Pal
    Norwegian University of Science and Technology.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Mason, Jeffrey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Johansson, Leif
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Sluzny, Chanan
    Appl Spectral Imaging, Migdal Haemeq.
    Handrick, Susann
    Charite.
    Prokop, Stefan
    Charite.
    Wegenast-Braun, Bettina
    German Centre Neurodegenerat Disease.
    Hornemann, Simone
    University of Zurich Hospital.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Lindgren, Mikael
    Norwegian University of Science and Technology.
    Heppner, Frank
    Charite.
    Jucker, Mathias
    German Centre Neurodegenerat Disease.
    Aguzzi, Adriano
    University of Zurich Hospital.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Monitoring amyloid formation and maturation in vitro and in vivo using LCO fluorescence in PRION, vol 6, issue , pp 13-132012Inngår i: PRION, Landes Bioscience , 2012, Vol. 6, s. 13-13Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 256.
    Nyström, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Bäck, Marcus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Imaging Amyloid Tissues Stained with Luminescent Conjugated Oligothiophenes by Hyperspectral Confocal Microscopy and Fluorescence Lifetime Imaging2017Inngår i: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, nr 128, artikkel-id e56279Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proteins that deposit as amyloid in tissues throughout the body can be the cause or consequence of a large number of diseases. Among these we find neurodegenerative diseases such as Alzheimers and Parkinsons disease afflicting primarily the central nervous system, and systemic amyloidosis where serum amyloid A, transthyretin and IgG light chains deposit as amyloid in liver, carpal tunnel, spleen, kidney, heart, and other peripheral tissues. Amyloid has been known and studied for more than a century, often using amyloid specific dyes such as Congo red and Thioflavin T (ThT) or Thioflavin (ThS). In this paper, we present heptamer-formyl thiophene acetic acid (hFTAA) as an example of recently developed complements to these dyes called luminescent conjugated oligothiophenes (LCOs). hFTAA is easy to use and is compatible with co-staining in immunofluorescence or with other cellular markers. Extensive research has proven that hFTAA detects a wider range of disease associated protein aggregates than conventional amyloid dyes. In addition, hFTAA can also be applied for optical assignment of distinct aggregated morphotypes to allow studies of amyloid fibril polymorphism. While the imaging methodology applied is optional, we here demonstrate hyperspectral imaging (HIS), laser scanning confocal microscopy and fluorescence lifetime imaging (FLIM). These examples show some of the imaging techniques where LCOs can be used as tools to gain more detailed knowledge of the formation and structural properties of amyloids. An important limitation to the technique is, as for all conventional optical microscopy techniques, the requirement for microscopic size of aggregates to allow detection. Furthermore, the aggregate should comprise a repetitive beta-sheet structure to allow for hFTAA binding. Excessive fixation and/or epitope exposure that modify the aggregate structure or conformation can render poor hFTAA binding and hence pose limitations to accurate imaging.

  • 257.
    Nyström, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions2015Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, nr 10101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from A beta 1-40, A beta 1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.

  • 258.
    Nyström, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Is the prevalent human prion protein 129M/V mutation a living fossil from a Paleolithic panzootic superprion pandemic?2014Inngår i: Prion, ISSN 1933-6896, E-ISSN 1933-690X, Vol. 8, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prion diseases are consistently associated with prion protein (PrPC) misfolding rendering a cascade of auto-catalytic self-perpetuation of misfolded PrP in an afflicted individual. The molecular process is intriguingly similar to all known amyloid diseases both local and systemic. The prion disease is also infectious by the transfer of misfolded PrP from one individual to the next. Transmissibility is surprisingly efficient in prion diseases and given the rapid disease progression following initial symptoms the prionoses stand out from other amyloidoses, which all may be transmissible under certain circumstances. The nature of the infectious prion as well as the genotype of the host is important for transmissibility. For hitherto unexplained reasons the majority of Europeans carry a missense mutation on one or both alleles of the PrP gene (PRNP), and hence express a variant of PrP with a substitution for valine (V) instead of methionine (M) in position 129. In fact the 129M/V variant is very common in all populations except for the Japanese. Sporadic Creutzfeldt-Jakob disease is a disease rarely striking people below the age of 60, where homozygosity especially 129MM is a very strong risk factor. Paradoxically, the 129M/V polymorphism suggestive of heterozygote advantage is one of the most clear cut disease associated traits of the human population, yet prion disease is extraordinarily rare. The genetic basis for how this trait spread with such prevalence within human populations is still target to investigations and deserves attention. This short essay represents a somewhat provocative hypothetical notion of a possible ancient significance of this polymorphism.

  • 259.
    Nyström, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Psonka-Antonczyk, Katarzyna M.
    Norwegian University of Science and Technology, Norway .
    Ellingsen, Pal Gunnar
    Norwegian University of Science and Technology, Norway .
    Johansson, Leif
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Reitan, Nina
    Norwegian University of Science and Technology, Norway .
    Handrick, Susann
    University of Medical Berlin, Germany .
    Prokop, Stefan
    University of Medical Berlin, Germany .
    Heppner, Frank L.
    University of Medical Berlin, Germany .
    Wegenast-Braun, Bettina M.
    German Centre Neurodegenerat Disease, Germany .
    Jucker, Mathias
    German Centre Neurodegenerat Disease, Germany .
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Torger Stokke, Bjorn
    Norwegian University of Science and Technology, Norway .
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter K R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Evidence for Age-Dependent in Vivo Conformational Rearrangement within A beta Amyloid Deposits2013Inngår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 8, nr 6, s. 1128-1133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deposition of aggregated A beta peptide in the brain is one of the major hallmarks of Alzheimers disease. Using a combination of two structurally different, but related, hypersensitive fluorescent amyloid markers, LCOs, reporting on separate ultrastructural elements, we show that conformational rearrangement occurs within A beta plaques of transgenic mouse models as the animals age. This important mechanistic insight should aid the design and evaluation of experiments currently using plaque load as readout.

  • 260.
    Nyström, Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Vahdat Shariat Panahi, Aida
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Westermark, Per
    d Department of Immunology , Genetics and Pathology, Uppsala University , Uppsala , Sweden.
    Westermark, Gunilla T.
    e Department of Medical Cell Biology , Uppsala University , Uppsala , Sweden.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lundmark, Katarzyna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Seed-dependent templating of murine AA amyloidosis2017Inngår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, nr sup1, s. 140-141Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 261.
    Odnell, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Influencing anaerobic digestion early stage processes for increased biomethane production from different substrate components2018Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Finding alternatives to petroleum-based energy sources is of interest since it could reduce the emissions of net carbon dioxide to the atmosphere by increasing the usage of renewable energy sources. To do so improvements are needed in the renewable energy production sector. Biogas production is of interest since the anaerobic digestion process can degrade many different biomolecules and is, contrary to e.g. bioethanol and biodiesel, not dependent on specific molecules. Thus, many wastes such as slaughterhouse waste, sludge from waste water treatment and lignocellulose residual material etc. can be used as substrates for biogas production. However, there are limitations in the degradation process depending on the composition of the selected substrate. To overcome these limitations such as inhibition of different microorganisms, or recalcitrant substrate, different methods can be used to increase the biogas production.

     In this study different substrates were selected and analyzed/treated for remedies of early stage rate limiting problems of the anaerobic digestion process. Different analyzes and techniques were selected depending on the limitations correlated to the main problematic component of the specific substrate.

     Improvements could be reached for the degradation of slaughterhouse waste by augmentation with the clay mineral zeolite. Addition of different enzymes to the substrate environment of different waste water treatment plant sludges resulted in limited life time of the selected enzymes. However, certain enzymes proved to be promising candidates with an effect of increased biogas production rate and yield for the time that the enzyme remained active. In an additional experiment, cellulolytic enzymes, naturally produced by a biogas producing microbial community, were induced, collected and added to a biogas experiment of ensiled forage ley, by which it was shown that these cellulases led to an increase in biogas production rate and yield. Thus, the studies demonstrate different techniques for improving the anaerobic digestion process of different types of substrates.

    Delarbeid
    1. Zeolites relieves inhibitory stress from high concentrations of long chain fatty acids
    Åpne denne publikasjonen i ny fane eller vindu >>Zeolites relieves inhibitory stress from high concentrations of long chain fatty acids
    2013 (engelsk)Inngår i: Waste Management, ISSN 0956-053X, E-ISSN 1879-2456, Vol. 33, nr 12, s. 2659-2663Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Protein and fat rich slaughterhouse waste is a very attractive waste stream for the production of biogas because of the high biochemical methane potential of the substrate. The material has however some drawbacks as the sole material for biogas production due to the production of several process disturbing metabolites such as ammonia, sulfides and long chain fatty acids. We can in this work present results that show that zeolites have the potential to relieve inhibitory stress from the presence of long chain fatty acids. Moreover, the results strongly indicate that it is mainly acetic acid consumers that are most negatively affected by long chain fatty acids and that the mechanism of stress relief is an adsorption of long chain fatty acids to the zeolites. In addition to this, it is shown that the effect is immediate and that only a small amount of zeolites is necessary to cancel the inhibitory effect of long chain fatty acids.

    sted, utgiver, år, opplag, sider
    Elsevier, 2013
    Emneord
    Zeolites, Anaerobic digestion, Long chain fatty acids, Inhibition, Slaughterhouse waste
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-103406 (URN)10.1016/j.wasman.2013.08.009 (DOI)000328309400010 ()
    Tilgjengelig fra: 2014-01-20 Laget: 2014-01-20 Sist oppdatert: 2018-05-07
    2. Activity, life time and effect of hydrolytic enzymes for enhanced biogas production from sludge anaerobic digestion
    Åpne denne publikasjonen i ny fane eller vindu >>Activity, life time and effect of hydrolytic enzymes for enhanced biogas production from sludge anaerobic digestion
    Vise andre…
    2016 (engelsk)Inngår i: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 103, s. 462-471Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    As an alternative to energy intensive physical methods, enzymatic treatment of sludge produced at wastewater treatment plants for increased hydrolysis and biogas production was investigated. Several hydrolytic enzymes were assessed with a focus on how enzyme activity and life time was influenced by sludge environments. It could be concluded that the activity life time of added enzymes was limited (amp;lt;24 h) in both waste activated sludge and anaerobic digester sludge environments and that this was, for the majority of enzymes, due to endogenous protease activity. In biogas in situ experiments, subtilisin at a 1% mixture on basis of volatile solids, was the only enzyme providing a significantly increased biomethane production of 37%. However, even at this high concentration, subtilisin could not hydrolyze all available substrate within the life time of the enzyme. Thus, for large scale implementation, enzymes better suited to the sludge environments are needed. (C) 2016 Elsevier Ltd. All rights reserved.

    sted, utgiver, år, opplag, sider
    PERGAMON-ELSEVIER SCIENCE LTD, 2016
    Emneord
    Wastewater treatment plant; Biogas; Enzyme; Protease; Subtilisin
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-132048 (URN)10.1016/j.watres.2016.07.064 (DOI)000383292100050 ()27498254 (PubMedID)
    Prosjekter
    BRC
    Forskningsfinansiär
    Swedish Energy Agency
    Merknad

    Funding Agencies|Swedish Energy Agency [P33609-1]

    Tilgjengelig fra: 2016-10-18 Laget: 2016-10-17 Sist oppdatert: 2018-10-11
    3. Enhanced biomethane production rate and yield from lignocellulosic ensiled forage ley by in situ anaerobic digestion treatment with endogenous cellulolytic enzymes
    Åpne denne publikasjonen i ny fane eller vindu >>Enhanced biomethane production rate and yield from lignocellulosic ensiled forage ley by in situ anaerobic digestion treatment with endogenous cellulolytic enzymes
    2017 (engelsk)Inngår i: Biotechnology for Biofuels, ISSN 1754-6834, E-ISSN 1754-6834, Vol. 10, artikkel-id 129Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Enzymatic treatment of lignocellulosic material for increased biogas production has so far focused on pretreatment methods. However, often combinations of enzymes and different physicochemical treatments are necessary to achieve a desired effect. This need for additional energy and chemicals compromises the rationale of using enzymes for low energy treatment to promote biogas production. Therefore, simpler and less energy intensive in situ anaerobic digester treatment with enzymes is desirable. However, investigations in which exogenous enzymes are added to treat the material in situ have shown mixed success, possibly because the enzymes used originated from organisms not evolutionarily adapted to the environment of anaerobic digesters. In this study, to examine the effect of enzymes endogenous to methanogenic microbial communities, cellulolytic enzymes were instead overproduced and collected from a dedicated methanogenic microbial community. By this approach, a solution with very high endogenous microbial cellulolytic activity was produced and tested for the effect on biogas production from lignocellulose by in situ anaerobic digester treatment. Results: Addition of enzymes, endogenous to the environment of a mixed methanogenic microbial community, to the anaerobic digestion of ensiled forage ley resulted in significantly increased rate and yield of biomethane production. The enzyme solution had an instant effect on more readily available cellulosic material. More importantly, the induced enzyme solution also affected the biogas production rate from less accessible cellulosic material in a second slower phase of lignocellulose digestion. Notably, this effect was maintained throughout the experiment to completely digested lignocellulosic substrate. Conclusions: The induced enzyme solution collected from a microbial methanogenic community contained enzymes that were apparently active and stable in the environment of anaerobic digestion. The enzymatic activity had a profound effect on the biogas production rate and yield, comparable with the results of many pretreatment methods. Thus, application of such enzymes could enable efficient low energy in situ anaerobic digester treatment for increased biomethane production from lignocellulosic material.

    sted, utgiver, år, opplag, sider
    BIOMED CENTRAL LTD, 2017
    Emneord
    Biogas; Lignocellulose; Cellulolytic; Cellulase; Enzyme; Hydrolysis; Biochemical methane potential (BMP); Anaerobic digestion; In situ
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-138248 (URN)10.1186/s13068-017-0814-0 (DOI)000401621100002 ()28523077 (PubMedID)
    Merknad

    Funding Agencies|Swedish Research Council [621-2009-4150]; Swedish Energy Agency through the Biogas Research Center [P33609-1]

    Tilgjengelig fra: 2017-06-14 Laget: 2017-06-14 Sist oppdatert: 2018-05-07
  • 262.
    Odnell, Anna
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan. Karshult Municipal Wastewater Treatment, Sweden.
    Recktenwald, Michael
    Kemira Oyj, Finland.
    Stensen, Katarina
    Tekniska Verken Linkoping AB, SE-58278 Linkoping, Sweden; Swedish Meteorol and Hydrol Institute, Sweden.
    Jonsson, Bengt-Harald
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Karlsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. InZymes Biotech AB, Gjuterigatan 1B, SE-58273 Linkoping, Sweden.
    Activity, life time and effect of hydrolytic enzymes for enhanced biogas production from sludge anaerobic digestion2016Inngår i: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 103, s. 462-471Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    As an alternative to energy intensive physical methods, enzymatic treatment of sludge produced at wastewater treatment plants for increased hydrolysis and biogas production was investigated. Several hydrolytic enzymes were assessed with a focus on how enzyme activity and life time was influenced by sludge environments. It could be concluded that the activity life time of added enzymes was limited (amp;lt;24 h) in both waste activated sludge and anaerobic digester sludge environments and that this was, for the majority of enzymes, due to endogenous protease activity. In biogas in situ experiments, subtilisin at a 1% mixture on basis of volatile solids, was the only enzyme providing a significantly increased biomethane production of 37%. However, even at this high concentration, subtilisin could not hydrolyze all available substrate within the life time of the enzyme. Thus, for large scale implementation, enzymes better suited to the sludge environments are needed. (C) 2016 Elsevier Ltd. All rights reserved.

  • 263.
    Ojamäe, Lars
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Aulin, Christian
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Käll, Per-Olov
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    IR and quantum-chemical studies of carboxylic acid and glycine adsorption on rutile TiO2 nanoparticles2006Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 296, nr 1, s. 71-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

      Nanocrystalline TiO2 powders of the rutile polymorph, synthesized by a sol–gel method, were treated with water solutions containing, respectively, formic, acetic, and citric acid and glycine in order to study the adsorption properties of these organic species. The samples were characterized by FTIR, Raman, powder XRD, and TEM. It was found that HCOOH, CH3COOH and HOC(COOH)(CH2COOH)2—but not NH2CH2COOH—adsorbed onto TiO2. The adsorption of HCOOH, CH3COOH and NH2CH2COOH onto the (110) surface of rutile was also studied by quantum-chemical periodic density functional theory (DFT) calculations. The organic molecules were from the computations found to adsorb strongly to the surfaces in a bridge-coordinating mode, where the two oxygens of the deprotonated carboxylic acid bind to two surface titanium ions. Surface relaxation is found to influence adsorption geometries and energies significantly. The results from DFT calculations and ab initio molecular-dynamics simulations of formic acid adsorption onto TiO2 are compared and match well with the experimental IR measurements, supporting the bridge-binding geometry of carboxylic-acid adsorption on the TiO2 nanoparticles.

  • 264.
    Ojamäe, Lars
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Pisani, C
    Theoretical characterization of divacancies at the surface and in bulk MgO1998Inngår i: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 109, nr 24, s. 10984-10995Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two types of divacancy at the (001) surface of MgO are theoretically studied and compared with the corresponding defect in the bulk: the pit, where a surface magnesium and the oxygen ion underneath are removed, and the tub, where both removed ions are at the surface. All calculations have been performed by means of the EMBED program which adopts an embedded-cluster approach in the frame of the Hartree-Fock (HF) approximation [C. Pisani F. Corà, R. Nada, and R. Orlando, Comput. Phys. Commun. 82, 139 (1994); C. Pisani and U. Birkenheuer, ibid. 96, 152 (1996)]; the semi-infinite host crystal for the study of the surface defects has been simulated with a four-layer slab. The energy released on formation of the divacancy from the two charged isolated vacancies is very high, almost 300 kcal/mol. The tub divacancy is the most stable, both as a neutral and as a singly charged defect. For the paramagnetic center (one electron trapped in the cavity), spin density data are provided and discussed with reference to results from electron paramagnetic resonance experiments and molecular cluster calculations [E. Giamello M. C. Paganini, D. Murphy, A. M. Ferrari, and G. Pacchioni, J. Phys. Chem. 101, 971 (1997)]. It is suggested that the tub divacancy is a common defect, if not the most common, at the highly dehydrated MgO surface.

  • 265.
    Ojamäe, Lars
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shavitt, Isaiah
    Ohio State Univ, Dept Chem, Columbus.
    Singer, Sherwin J
    Ohio State Univ, Dept Chem, Columbus.
    Potential models for simulations of the solvated proton in water1998Inngår i: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 109, nr 13, s. 5547-5564Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analytical potential models are designed for simulations of water with excess protons. The potentials describe both intramolecular and intermolecular interactions, and allow dissociation and formation of the species (H 2 O) n H + . The potentials are parametrized in the form of interactions between H + and O 2− ions, with additional three-body (H–O–H) interaction terms and self-consistent treatment of the polarizability of the oxygen ions. The screening of electrostatic interactions caused by the overlap of the electron clouds in the real molecules is modeled by functions modifying the electric field at short distances. The model was derived by fitting to the potential surface of the H 5 O + 2 ion and other species, as obtained from ab initio MP2 calculations employing an extensive basis set. Emphasis was put on modeling the potential-energy surface for the proton-transfer reaction. Potential-surface profiles, geometry-optimizedstructures and formation energies of H 5 O + 2 , protonated water clusters [H + (H 2 O) n , n=2–4] and water clusters [(H 2 O) n , n=1–6] using these potentials are presented and compared to results using quantum-chemical calculations. The potential models can well reproduce ab initio results for the H 5 O + 2 ion, and can provide formation energies and structures of both protonated-water and water-only clusters that agree favorably with ab initio MP2 calculations.

  • 266.
    Ojamäe, Lars
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    SHAVITT, Isaiha
    Department of Chemistry, The Ohio State University.
    SINGER, Sherwin J.
    Department of Chemistry, The Ohio State University.
    POTENTIAL-ENERGY SURFACES AND VIBRATIONAL-SPECTRA OF H5O2+ AND LARGER HYDRATED PROTON COMPLEXES1995Inngår i: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 56, nr 29, s. 657-668Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article presents calculations of the structure, binding energetics, potential energy surfaces, and vibrational spectra of the H5O ion. The 15-dimensional potential energy surface for the seven nuclei in the ionic complex was computed by pointwise ab initio Møller-Plesset second-order perturbation (MP2) calculations, using the correlation-consistent pVTZ basis set augmented with diffuse basis functions on oxygen. The potential energy surface for the proton-transfer mechanism was investigated, and the effects of surrounding water molecules on the proton-transfer potential energy curve was studied. Density functional calculations for the proton-transfer potential surface are compared to the MP2 results. Geometry-optimized structures, binding energies, and harmonic vibrational spectra of H5O and H9O are presented. The energy-minimum structure of H5O using the augmented pVTZ basis set is of C2 symmetry, whereas for H9O, using the TZ2P basis set, it is of C3 symmetry. The H-bonded OH stretching harmonic frequency of H5O is very low, 913 cm−1, whereas for H9O it is 2927 cm−1. The subspace spanned by the hydrogen-bonded OH distance and the OO distance were used in one- and two-dimensional calculations of the anharmonic vibrational spectrum using collocation methods. The coupling of the OH stretch with the OO vibration causes a redshift and the anharmonicity a blueshift of the OH frequency: the resulting fundamental frequency of the H-bonded OH vibration is 1275 cm−1. Zero-point energies of the proton vibration and pathways for exchange of protons within H5O are discussed. © 1995 John Wiley & Sons, Inc.

  • 267.
    Ottosson, Nina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Silverå Ejneby, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Yazdi, Samira
    Stockholm University, Sweden.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindahl, Erik
    Stockholm University, Sweden; KTH Royal Institute Technology, Sweden.
    Elinder, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    A drug pocket at the lipid bilayer-potassium channel interface2017Inngår i: Science Advances, ISSN 0036-8156, E-ISSN 2375-2548, Vol. 3, nr 10, artikkel-id e1701099Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many pharmaceutical drugs against neurological and cardiovascular disorders exert their therapeutic effects by binding to specific sites on voltage-gated ion channels of neurons or cardiomyocytes. To date, all molecules targeting known ion channel sites bind to protein pockets that are mainly surrounded by water. We describe a lipid-protein drug-binding pocket of a potassium channel. We synthesized and electrophysiologically tested 125 derivatives, analogs, and related compounds to dehydroabietic acid. Functional data in combination with docking and molecular dynamics simulations mapped a binding site for small-molecule compounds at the interface between the lipid bilayer and the transmembrane segments S3 and S4 of the voltage-sensor domain. This fundamentally new binding site for small-molecule compounds paves the way for the design of new types of drugs against diseases caused by altered excitability.

  • 268.
    Ottosson, Nina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nolting, Andreas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Urban
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lund, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Ruda, Katinka
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Svensson, Stefan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Elinder, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability2015Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, nr 13278Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Voltage-gated ion channels generate cellular excitability, cause diseases when mutated, and act as drug targets in hyperexcitability diseases, such as epilepsy, cardiac arrhythmia and pain. Unfortunately, many patients do not satisfactorily respond to the present-day drugs. We found that the naturally occurring resin acid dehydroabietic acid (DHAA) is a potent opener of a voltage-gated K channel and thereby a potential suppressor of cellular excitability. DHAA acts via a non-traditional mechanism, by electrostatically activating the voltage-sensor domain, rather than directly targeting the ion-conducting pore domain. By systematic iterative modifications of DHAA we synthesized 71 derivatives and found 32 compounds more potent than DHAA. The most potent compound, Compound 77, is 240 times more efficient than DHAA in opening a K channel. This and other potent compounds reduced excitability in dorsal root ganglion neurons, suggesting that resin-acid derivatives can become the first members of a new family of drugs with the potential for treatment of hyperexcitability diseases.

  • 269.
    Owenius, Rikard
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Jarl, Anngelica
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Jonsson, Bengt-Harald
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Carlsson, Uno
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    GroEL-induced topological dislocation of a substrate protein β-sheet core: a solution EPR spin–spin distance study2010Inngår i: Journal of chemical biology, ISSN 1864-6158, E-ISSN 1864-6166, Vol. 3, nr 3, s. 127-39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Hsp60-type chaperonin GroEL assists in the folding of the enzyme human carbonic anhydrase II (HCA II) and protects it from aggregation. This study was aimed to monitor conformational rearrangement of the substrate protein during the initial GroEL capture (in the absence of ATP) of the thermally unfolded HCA II molten-globule. Single- and double-cysteine mutants were specifically spin-labeled at a topological breakpoint in the β-sheet rich core of HCA II, where the dominating antiparallel β-sheet is broken and β-strands 6 and 7 are parallel. Electron paramagnetic resonance (EPR) was used to monitor the GroEL-induced structural changes in this region of HCA II during thermal denaturation. Both qualitative analysis of the EPR spectra and refined inter-residue distance calculations based on magnetic dipolar interaction show that the spin-labeled positions F147C and K213C are in proximity in the native state of HCA II at 20 °C (as close as ∼8 Å), and that this local structure is virtually intact in the thermally induced molten-globule state that binds to GroEL. In the absence of GroEL, the molten globule of HCA II irreversibly aggregates. In contrast, a substantial increase in spin–spin distance (up to >20 Å) was observed within minutes, upon interaction with GroEL (at 50 and 60 °C), which demonstrates a GroEL-induced conformational change in HCA II. The GroEL binding-induced disentanglement of the substrate protein core at the topological break-point is likely a key event for rearrangement of this potent aggregation initiation site, and hence, this conformational change averts HCA II misfolding.

  • 270.
    Pathak, Surajit
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Meng, Wen-Jian
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Sichuan University, Peoples R China.
    Kumar Nandy, Suman
    University of Kalyani, India.
    Ping, Jie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Bisgin, Atil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Helmfors, Linda
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Waldmann, Patrik
    Linköpings universitet, Institutionen för datavetenskap, Statistik. Linköpings universitet, Filosofiska fakulteten.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner2015Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, nr 42, s. 44758-44780Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan (R) miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-alpha, IL-1 beta, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1 alpha were increased, and IFN-gamma expression was decreased after radiation, whereas, IL-6, IFN-gamma, TNF-alpha, IL-1 beta, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1 alpha were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

  • 271.
    Pearce, Ruth
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Becker, Elin
    Chalmers Göteborg.
    Haglin, A
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Söderlind, Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Käll, Per-Olov
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Fysikalisk Kemi. Linköpings universitet, Tekniska högskolan.
    Yakimova, Rositsa
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Skoglundh, Magnus
    Chalmers, Göteborg.
    Lloyd Spetz, Anita
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Understanding the gas sensor response of ZnO and Ga:ZnO2010Inngår i: IMCS13, 2010, s. 376-Konferansepaper (Fagfellevurdert)
  • 272.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Experimental and quantum-chemical studies of the surface interactions between organic molecules and nanocrystals of (a) RE2O3 (RE = Y or Gd); and (b) TiOb22005Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The increasing interest for using nanocrystals in bio-medical and optical applications has highlighted the need of molecular functionalisation of nanocrystals. Knowledge of how to attach molecules to the nanocrystal surface is a key factor. This thesis focuses on the surface interactions between nanocrystals of (a) RE2O3 (RE = Y or Gd); and (b) TiO2 and organic molecules, which have been studied experimentally and by quantum-chemical calculations with the intent to elucidate the chemisorption characteristics such as adsorption geometries and energies.

    (a) RE2O3 nanocrystal synthesis was performed by a colloidal method based on polyols and by a rapid combustion method. The products were experimentally characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), infrared spectroscopy (IR), Raman, and X-ray photoelectron spectroscopy (XPS). By quantum chemical calculations the chemisorption of formic acid, DEG, water and TMOS at the surface of RE12O18 clusters was studied. From comparison between calculated and experimental vibrational spectra, the binding mode for formic acid on RE2O3 was inferred to be of bridge or bidentate type. XPS and IR showed that DEG chemisorbs on the particle surface and experimental IR spectra of DEG chemisorbed on RE2O3 were consistent with an adsorption mode where the hydroxyl groups are deprotonated according to the quantum-chemical computations.

    (b) Synthesis of single-phase rutile TiO2 nanocrystals was done by a sol-gel method and the nanocrystals was subsequently functionalized by organic acids and glycine. Quantum-chemical studies indicate that formic- and acetic acid adsorbs in a bridge or monodentate binding mode, while glycine is suggested to adsorb as a zwitterion with bridge bonded carboxylic group and a hydrogen bonded amino group. However, spectroscopic data showed that the amino acid, unlike the other acids did not adsorb on TiO2 under the given experimental conditions.

    Delarbeid
    1. Synthesis and characterisation of Gd2O3 nanocrystals functionalised by organic acids
    Åpne denne publikasjonen i ny fane eller vindu >>Synthesis and characterisation of Gd2O3 nanocrystals functionalised by organic acids
    Vise andre…
    2005 (engelsk)Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 288, nr 1, s. 140-148Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Nanocrystals of Gd2O3 have been prepared by various methods, using, e.g., trioctylphosphine oxide (TOPO), diethylene glycol (DEG) or glycine. The crystalline particles were of sizes 5 to 15 nm. Different carboxylic acids, e.g., oleic acid or citric acid, were adsorbed onto the surface of the particles made with DEG. IR measurements show that the molecules coordinate to the Gd2O3 surface via the carboxylate group in a bidentate or bridging manner. The organic-acid/particle complexes were characterised by XRPD, TEM, FTIR, Raman, and XPS.

    Emneord
    Nanocrystals; Synthesis; Functionalisation; IR; XPS
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13295 (URN)10.1016/j.jcis.2005.02.089 (DOI)000229861600019 ()
    Tilgjengelig fra: 2008-05-21 Laget: 2008-05-21 Sist oppdatert: 2017-12-13
    2. Surface interactions between Y2O3 nanocrystals and organic molecules—an experimental and quantum-chemical study
    Åpne denne publikasjonen i ny fane eller vindu >>Surface interactions between Y2O3 nanocrystals and organic molecules—an experimental and quantum-chemical study
    Vise andre…
    2005 (engelsk)Inngår i: Surface Science, ISSN 0039-6028, E-ISSN 1879-2758, Vol. 592, nr 1-3, s. 124-140Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The surface interactions between Y2O3 nanocrystals and the organic molecules formic acid, diethylene glycol (DEG), and tetramethoxy silane (TMOS), have been studied experimentally and by quantum chemical calculations with the intent to elucidate the chemisorption characteristics such as adsorbate vibrational spectra and adsorption structures. Nanocrystal synthesis was performed by a colloidal method based on polyols and by a rapid combustion method. The products were experimentally characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS).

    In the quantum chemical calculations, the B3LYP hybrid density functional ab initio method was used to study the chemisorption of formic acid, DEG and TMOS at the surface of Y12O18 clusters. From a comparison of calculated and experimental vibrational spectra, the binding mode for formic acid on Y2O3 was inferred to be of bridge or bidentate type. The XPS and FT-IR experiments showed that DEG is chemisorbed on the particle surface. The experimental IR spectra of DEG chemisorbed on Y2O3 were consistent with an adsorption mode where the hydroxyl groups are deprotonated according to the quantum-chemical computations. The adsorption energy is of the order of 370 kJ mol−1 for formic acid, 550 kJ mol−1 for DEG, and 60 kJ mol−1 for TMOS, according to the quantum chemical calculations.

    Emneord
    Ab initio quantum chemical methods and calculations; X-ray photoelectron spectroscopy; Chemisorption; Yttrium; Alcohols; Carboxylic acid; Silane
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13296 (URN)10.1016/j.susc.2005.07.027 (DOI)000232461700015 ()
    Tilgjengelig fra: 2008-05-21 Laget: 2008-05-21 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Towards Biocompatibility of RE2O3 Nanocrystals − Water and Organic Molecules Chemisorbed on Gd2O3 and Y2O3 Nanocrystals Studied by Quantum-Chemical Computations
    Åpne denne publikasjonen i ny fane eller vindu >>Towards Biocompatibility of RE2O3 Nanocrystals − Water and Organic Molecules Chemisorbed on Gd2O3 and Y2O3 Nanocrystals Studied by Quantum-Chemical Computations
    2006 (engelsk)Inngår i: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 6, nr 9, s. 2004-2008Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Nanocrystals of Gd2O3/Y2O3 and their interaction with water, formic acid, diethylene glycol (DEG), and tetramethoxy silane (TMOS) have been studied by quantum-chemical calculations at the B3LYP level using solvent-coated clusters of gadolinia and yttria. Adsorption energies, surface geometries, electronic structures, and excitation spectra were calculated. The results concerning adsorption strengths and superparamagnetic high-spin states can provide insight into the design of molecular-capped RE2O3 nanocrystals to be used in vivo.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-36184 (URN)10.1021/nl061185w (DOI)000240465100030 ()30419 (Lokal ID)30419 (Arkivnummer)30419 (OAI)
    Tilgjengelig fra: 2009-10-10 Laget: 2009-10-10 Sist oppdatert: 2017-12-13
    4. IR and quantum-chemical studies of carboxylic acid and glycine adsorption on rutile TiO2 nanoparticles
    Åpne denne publikasjonen i ny fane eller vindu >>IR and quantum-chemical studies of carboxylic acid and glycine adsorption on rutile TiO2 nanoparticles
    2006 (engelsk)Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 296, nr 1, s. 71-78Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

      Nanocrystalline TiO2 powders of the rutile polymorph, synthesized by a sol–gel method, were treated with water solutions containing, respectively, formic, acetic, and citric acid and glycine in order to study the adsorption properties of these organic species. The samples were characterized by FTIR, Raman, powder XRD, and TEM. It was found that HCOOH, CH3COOH and HOC(COOH)(CH2COOH)2—but not NH2CH2COOH—adsorbed onto TiO2. The adsorption of HCOOH, CH3COOH and NH2CH2COOH onto the (110) surface of rutile was also studied by quantum-chemical periodic density functional theory (DFT) calculations. The organic molecules were from the computations found to adsorb strongly to the surfaces in a bridge-coordinating mode, where the two oxygens of the deprotonated carboxylic acid bind to two surface titanium ions. Surface relaxation is found to influence adsorption geometries and energies significantly. The results from DFT calculations and ab initio molecular-dynamics simulations of formic acid adsorption onto TiO2 are compared and match well with the experimental IR measurements, supporting the bridge-binding geometry of carboxylic-acid adsorption on the TiO2 nanoparticles.

    Emneord
    Titanium oxide; Nanoparticle; Adsorption; Carboxylic acid; Glycine; FTIR; Raman; Quantum-chemical calculations
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-36193 (URN)10.1016/j.jcis.2005.08.037 (DOI)000236185600010 ()30468 (Lokal ID)30468 (Arkivnummer)30468 (OAI)
    Tilgjengelig fra: 2009-10-10 Laget: 2009-10-10 Sist oppdatert: 2017-12-13
  • 273.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    On the Existence of Nonfunctional Materials2018Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 30, nr 17, s. 5797-5798Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 274.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Simple Chemical Vapor Deposition Experiment2014Inngår i: Journal of Chemical Education, ISSN 0021-9584, E-ISSN 1938-1328, Vol. 91, nr 9, s. 1495-1497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chemical vapor deposition (CVD) is a process commonly used for the synthesis of thin films for several important technological applications, for example, microelectronics, hard coatings, and smart windows. Unfortunately, the complexity and prohibitive cost of CVD equipment makes it seldom available for undergraduate chemistry students. Here, a simple CVD experiment designed to give hands-on experience with this technique using common chemical laboratory equipment is outlined. The experiment is suitable for an upper-level or graduate course on inorganic chemistry, materials chemistry or materials science. In the experiment, crystalline thin films of titanium nitride (TiN) are deposited using titanium tetrachloride, hydrogen, and nitrogen gas in an experimental setup based on a tithe furnace and common safety flasks. Typically, crystalline TiN films with some incorporation of TiO2 are deposited in this experiment. The experiment has been used in the teaching of both master and doctorial students.

  • 275.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Time as the Fourth Dimension: Opening up New Possibilities in Chemical Vapor Deposition2016Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 28, nr 3, s. 691-699Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thin films of inorganic materials are essential to several technologies we take for granted in our everyday lives. They form the basis of touch screens in smart phones and the electronic components in computers. Dating back more than a century, chemical vapor deposition (CVD) is one of the most common methods to form these films. In CVD, the atoms needed for the thin film are typically supplied by a continuous flow of gaseous precursor molecules and incorporated into the film by gas phase and surface chemical reactions. The continuous demand for more precise thin film fabrication on more complex shapes at lower temperatures sets a demand for more advanced CVD methods. The development of better designed precursor molecules is one important path to evolve CVD; the other path is to evolve the way in which we do CVD. In this perspective I will describe how using time as a fourth dimension in CVD can enable fabrication of new thin film materials and material structures at lower temperatures and on more complex substrate geometries by accessing new types of CVD chemistries available in time-resolved CVD.

  • 276.
    Pedersen, Henrik
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Alling, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska fakulteten.
    Högberg, Hans
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tunnfilmsfysik. Linköpings universitet, Tekniska fakulteten.
    Ektarawong, Annop
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska fakulteten. Chulalongkorn Univ, Thailand; Commiss Higher Educ, Thailand.
    Thermodynamic stability of hexagonal and rhombohedral boron nitride under chemical vapor deposition conditions from van der Waals corrected first principles calculations2019Inngår i: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 37, nr 4, artikkel-id 040603Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thin films of boron nitride (BN), particularly the sp(2)-hybridized polytypes hexagonal BN (h-BN) and rhombohedral BN (r-BN), are interesting for several electronic applications, given the bandgaps in the UV. They are typically deposited close to thermal equilibrium by chemical vapor deposition (CVD) at temperatures and pressures in the regions 1400-1800K and 1000-10000Pa, respectively. In this letter, the authors use the van der Waals corrected density functional theory and thermodynamic stability calculations to determine the stability of r-BN and compare it to that of h-BN as well as to cubic BN and wurtzitic BN. The authors find that r-BN is the stable sp(2)-hybridized phase at CVD conditions, while h-BN is metastable. Thus, their calculations suggest that thin films of h-BN must be deposited far from thermal equilibrium.

  • 277.
    Pedersen, Henrik
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Elliott, Simon D.
    National University of Ireland University of Coll Cork, Ireland .
    Studying chemical vapor deposition processes with theoretical chemistry2014Inngår i: Theoretical Chemistry accounts, ISSN 1432-881X, E-ISSN 1432-2234, Vol. 133, nr 5, s. 1476-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In a chemical vapor deposition (CVD) process, a thin film of some material is deposited onto a surface via the chemical reactions of gaseous molecules that contain the atoms needed for the film material. These chemical reactions take place on the surface and in many cases also in the gas phase. To fully understand the chemistry in the process and thereby also have the best starting point for optimizing the process, theoretical chemical modeling is an invaluable tool for providing atomic-scale detail on surface and gas phase chemistry. This overview briefly introduces to the non-expert the main concepts, history and application of CVD, including the pulsed CVD variant known as atomic layer deposition, and put into perspective the use of theoretical chemistry in modeling these processes.

  • 278.
    Pedersen, Henrik
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Lin, Ching-Chi
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    On the change of preferential growth orientation in chemical vapor deposition of titanium carbide by aromatic hydrocarbon precursors2013Inngår i: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 31, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thin films of titanium carbide grown by chemical vapor deposition exhibit a strong preferential (111) growth direction if aromatic hydrocarbons, such as benzene, are used as a carbon precursor. If aliphatic hydrocarbons such as methane are used, growth on the (100) surface is preferred. In this study, quantum chemical computations are used to study the adsorption of benzene and methane on the (100) and (111) surfaces to provide an explanation for the changed growth behavior. The adsorption energy of benzene is found to be approximately twice as high on the (111) surface as compared to the (100) surface, and adsorption studies further suggest that benzene chemisorbs on the (111) surface, while it physisorbs on the (100) surface. The studies reveal no significant differences in adsorption energy or behavior for methane on the two surfaces. The authors propose that the higher benzene adsorption energy and different adsorption behavior on the (111) surface are the explanations for the preferential growth orientation.

  • 279.
    Pedersen, Henrik
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Towards Biocompatibility of RE2O3 Nanocrystals − Water and Organic Molecules Chemisorbed on Gd2O3 and Y2O3 Nanocrystals Studied by Quantum-Chemical Computations2006Inngår i: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 6, nr 9, s. 2004-2008Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nanocrystals of Gd2O3/Y2O3 and their interaction with water, formic acid, diethylene glycol (DEG), and tetramethoxy silane (TMOS) have been studied by quantum-chemical calculations at the B3LYP level using solvent-coated clusters of gadolinia and yttria. Adsorption energies, surface geometries, electronic structures, and excitation spectra were calculated. The results concerning adsorption strengths and superparamagnetic high-spin states can provide insight into the design of molecular-capped RE2O3 nanocrystals to be used in vivo.

  • 280.
    Persson, Kristin M
    et al.
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska högskolan.
    Gabrielsson, Roger
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sawatdee, Anurak
    Department of Printed Electronics, Acreo Swedish ICT AB, Norrköping, Sweden.
    Nilsson, David
    Department of Printed Electronics, Acreo Swedish ICT AB, Norrköping, Sweden.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Berggren, Magnus
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska högskolan.
    Electronic control over detachment of a self-doped water-soluble conjugated polyelectrolyte2014Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, nr 21, s. 6257-6266Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Water-soluble conducting polymers are of interest to enable more versatile processing in aqueous media as well as to facilitate interactions with biomolecules. Here, we report a substituted poly(3,4-ethylenedioxythiophene) derivative (PEDOT-S:H) that is fully water-soluble and selfdoped. When electrochemically oxidizing a PEDOT-S:H thin film, the film detaches from the under-laying electrode. The oxidation of PEDOT-S:H starts with an initial phase of swelling followed by cracking before it finally disrupts and detaches from the electrode. We investigated the detachment mechanism and found that parameters such as the size, charge and concentration of ions in the electrolyte, the temperature and also the pH influence the characteristics of detachment. When oxidizing PEDOT-S:H, the positively charged polymer backbone is balanced by anions from the electrolyte solution and also by the sulphonate groups on the side chains (more self-doping). From our experiments, we conclude that detachment of the PEDOT-S:H film upon oxidation occurs in part due to swelling caused by an inflow of solvated anions and associated water, and in part due to rearrangements and strain within the film, caused by more self-doping. We believe that PEDOT-S:H detachment can be of interest in a number of different applications, including addressed and active control of the release of materials such as biomolecules and cell cultures.

  • 281.
    Ping Heidi Iu, Yan
    et al.
    Queen Elizabeth Hospital, Peoples R China.
    Helander, Sara
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Zimdahl Kahlin, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Wah Cheng, Chun
    Queen Elizabeth Hospital, Peoples R China.
    Chung Shek, Chi
    Queen Elizabeth Hospital, Peoples R China.
    Ho Leung, Moon
    Queen Elizabeth Hospital, Peoples R China.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Mårtensson, Lars-Göran
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindqvist Appell, Malin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    One amino acid makes a difference-Characterization of a new TPMT allele and the influence of SAM on TPMT stability2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 46428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A amp;gt; C, named TPMT*41, together with the more common variant *3C c.719A amp;gt; G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively. We show that the patient heterozygote for c.719A amp;gt; C has intermediate enzymatic activity in red blood cells. Furthermore, in vitro studies, using recombinant protein, show that TPMT p.Y240S is less stable than both TPMTwt and TPMT p.Y240C. The addition of SAM increases the stability and, in agreement with Isothermal Titration Calorimetry (ITC) data, higher molar excess of SAM is needed in order to stabilize TPMT p.Y240C and TPMT p.Y240S compared to TPMTwt. Molecular dynamics simulations show that the loss of interactions is most severe for Y240S, which agrees with the thermal stability of the mutations. In conclusion, our study shows that SAM increases the stability of TPMT and that changing only one amino acid can have a dramatic effect on TPMT stability and activity.

  • 282.
    Poxson, David
    et al.
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Karady, Michal
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Gabrielsson, Roger
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Alkattan, Aziz Yousif Aziz
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Gustavsson, Anna
    Umeå Plant Science Centre, Department of Plant Physiology, Umeå University, Umeå, Sweden.
    Doyle, Siamsa M.
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Robert, Stéphanie
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Ljung, Karin
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Grebe, Markus
    Umeå Plant Science Centre, Department of Plant Physiology, Umeå University, Umeå, Sweden; Plant Physiology, Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Golm, Germany.
    Simon, Daniel
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Berggren, Magnus
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Regulating plant physiology with organic electronics.2017Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 18, s. 4597-4602Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

  • 283.
    Psonka-Antonczyk, Katarzyna M.
    et al.
    Department of Physics, Norwegian University of Science and Technology NTNU, Trondheim, Norway.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Johansson, Leif
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Department of Physics, Norwegian University of Science and Technology NTNU, Trondheim, Norway.
    Stokke, Björn T.
    Department of Physics, Norwegian University of Science and Technology NTNU, Trondheim, Norway.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nanoscale Structure and Spectroscopic Probing of A beta 1-40 Fibril Bundle Formation2016Inngår i: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 4, artikkel-id 44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid plaques composed of fibrillar Amyloid-beta (A beta) are hallmarks of Alzheimers disease. However, A beta fibrils are morphologically heterogeneous. Conformation sensitive luminescent conjugated oligothiophenes (LCOs) are versatile tools for monitoring such fibril polymorphism in vivo and in vitro. Biophysical methods applied on in vitro generated A beta fibrils, stained with LCOs with different binding and fluorescence properties, can be used to characterize the A beta fibrillation in depth, far beyond that possible for in vivo generated amyloid plaques. In this study, in vitro fibrillation of the A beta 1-40 peptide was monitored by time-lapse transmission electron microscopy, LCO fluorescence, and atomic force microscopy. Differences in the LCO binding in combination with nanoscale imaging revealed that spectral variation correlated with fibrils transforming from solitary filaments (empty set similar to 2.5 nm) into higher order bundled structures (empty set similar to 5 nm). These detailed in vitro experiments can be used to derive data that reflects the heterogeneity of in vivo generated A beta plaques observed by LCO fluorescence. Our work provides new structural basis for targeted drug design and molecular probe development for amyloid imaging.

  • 284.
    Rasmussen, Jay
    et al.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Mahler, Jasmin
    University of Tubingen, Germany.
    Beschorner, Natalie
    University of Tubingen, Germany.
    Kaeser, Stephan A.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Haesler, Lisa M.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Baumann, Frank
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Portelius, Erik
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Blennow, Kaj
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Lashley, Tammaryn
    UCL, England.
    Fox, Nick C.
    UCL, England.
    Sepulveda-Falla, Diego
    University of Medical Centre Hamburg Eppendorf, Germany; University of Antioquia, Colombia; University of Antioquia, Colombia.
    Glatzel, Markus
    University of Medical Centre Hamburg Eppendorf, Germany.
    Oblak, Adrian L.
    Indiana University of School Med, IN 46202 USA.
    Ghetti, Bernardino
    Indiana University of School Med, IN 46202 USA.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Staufenbiel, Matthias
    University of Tubingen, Germany.
    Walker, Lary C.
    Emory University, GA 30329 USA.
    Jucker, Mathias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimers disease2017Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 49, s. 13018-13023Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-beta peptide (A beta) has been shown to adopt distinct structural conformations with different biological activities, we asked whether A beta can assume structurally and functionally distinct conformations within the brain. To this end, we analyzed the LCO-stained cores of beta-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimers disease (AD) or sporadic (idiopathic) AD (sAD). The spectral attributes of LCO-bound plaques varied markedly in the brain, but the mean spectral properties of the amyloid cores were generally similar in all three cortical regions of individual patients. Remarkably, the LCO amyloid spectra differed significantly among some of the familial and sAD subtypes, and between typical patients with sAD and those with posterior cortical atrophy AD. Neither the amount of A beta nor its protease resistance correlated with LCO spectral properties. LCO spectral amyloid phenotypes could be partially conveyed to A beta plaques induced by experimental transmission in a mouse model. These findings indicate that polymorphic A beta-amyloid deposits within the brain cluster as clouds of conformational variants in different AD cases. Heterogeneity in the molecular architecture of pathogenic A beta among individuals and in etiologically distinct subtypes of AD justifies further studies to assess putative links between A beta conformation and clinical phenotype.

  • 285.
    Ravichandran, Ranjithkumar
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Islam, M. M.
    Karolinska Institute, Sweden.
    Alarcon, E. I.
    University of Ottawa, Canada; Fac Med, Canada.
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wang, S.
    Uppsala University, Sweden.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hilborn, J.
    Uppsala University, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Correction: Functionalised type-1 collagen as a hydrogel building block for bio-orthogonal tissue engineering applications (vol 4, pg 318, 2016)2017Inngår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 5, nr 26, s. 5284-5284Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 286.
    Ravichandran, Ranjithkumar
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Islam, M. M.
    Karolinska Institute, Sweden; .
    Alarcon, E. I.
    University of Ottawa, Canada; .
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wang, S.
    Uppsala University, Sweden.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hilborn, J.
    Uppsala University, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications2016Inngår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, nr 2, s. 318-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

  • 287.
    Richter, Katrin
    et al.
    Justus Liebig Univ Giessen, Germany.
    Koch, Christian
    Justus Liebig Univ Giessen, Germany.
    Perniss, Alexander
    Justus Liebig Univ Giessen, Germany.
    Wolf, Philipp M.
    Justus Liebig Univ Giessen, Germany.
    Schweda, Elke
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wichmann, Sven
    Justus Liebig Univ Giessen, Germany.
    Wilker, Sigrid
    Justus Liebig Univ Giessen, Germany.
    Magel, Ilona
    Justus Liebig Univ Giessen, Germany.
    Sander, Michael
    Justus Liebig Univ Giessen, Germany.
    McIntosh, J. Michael
    Univ Utah, UT 84112 USA; George E Wahlen Vet Affairs Med Ctr, UT 84148 USA; Univ Utah, UT 84108 USA.
    Padberg, Winfried
    Justus Liebig Univ Giessen, Germany.
    Grau, Veronika
    Justus Liebig Univ Giessen, Germany.
    Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1 beta Release by Pulmonary Epithelial Cells2018Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 8, artikkel-id 1979Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1 beta. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1 beta release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits alpha 7, alpha 9, and/or alpha 10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae.

  • 288.
    Ries, Jonas
    et al.
    EMBL Heidelberg, Germany .
    Udayar, Vinod
    University of Zurich, Switzerland .
    Soragni, Alice
    ETH, Switzerland .
    Hornemann, Simone
    University of Zurich, Switzerland .
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Riek, Roland
    ETH, Switzerland .
    Hock, Christoph
    University of Zurich, Switzerland .
    Ewers, Helge
    ETH, Switzerland .
    Aguzzi, Adriano A.
    University of Zurich, Switzerland .
    Rajendran, Lawrence
    University of Zurich, Switzerland .
    Superresolution Imaging of Amyloid Fibrils with Binding-Activated Probes2013Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 4, nr 7, s. 1057-1061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein misfolding into amyloid-like aggregates underlies many neurodegenerative diseases. Thus, insights into the structure and function of these amyloids will provide valuable information on the pathological mechanisms involved and aid in the design of improved drugs for treating amyloid-based disorders. However, determining the structure of endogenous amyloids at high resolution has been difficult. Here we employ binding-activated localization microscopy (BALM) to acquire superresolution images of alpha-synuclein amyloid fibrils with unprecedented optical resolution. We propose that BALM imaging can be extended to study the structure of other amyloids, for differential diagnosis of amyloid-related diseases and for discovery of drugs that perturb amyloid structure for therapy.

  • 289.
    Rouf, Polla
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    O´brien, Nathan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Rönnby, Karl
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Samii, Rouzbeh
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Ivanov, Ivan Gueorguiev
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska fakulteten.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    The Endocyclic Carbon Substituent of Guanidinate and Amidinate Precursors Controlling Atomic Layer Deposition of InN Films2019Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 123, nr 42, s. 25691-25700Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Indium nitride (InN) is an interesting material for future high-frequency electronics due to its high electron mobility. The problematic deposition of InN films currently prevents full exploration of InN-based electronics. We present studies of atomic layer deposition (ALD) of InN using In precursors with bidentate ligands forming In-N bonds: tris(N,N-dimethyl-N,N -diisopropylguanidinato)indium(III), tris(N,N-diisopropylamidinato)indium(III), and tris(N,N-diisopropylformamidinato)indium(III). These compounds form a series were the size of the substituent on the endocyclic position decreases from -NMe2 to -Me and to -H, respectively. We show that when the size of the substituent decreases, the InN films deposited have a better crystalline quality, of better optical quality, lower roughness, and an In/N ratio closer to unity. From quantum chemical calculations, we show that the smaller substituents lead to less steric repulsion and weaker bonds between the ligand and In center. We propose that these effects render a more favored surface chemistry for the nitridation step in the ALD cycle, which explains the improved film properties.

  • 290.
    Rouhbakhsh, Zeinab
    et al.
    Not Found:Linkoping Univ, Dept Phys Chem and Biol, Div Mol Phys, Lab Mol Mat, S-58183 Linkoping, Sweden; Linkoping Univ, Dept Phys, Div Chem, Chem and Biol, S-58183 Linkoping, Sweden.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Martinsson, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Svärd, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Back, Marcus
    Ferdowsi Univ Mashhad, Iran.
    Housaindokht, Mohammad R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Ferdowsi Univ Mashhad, Iran.
    Selegård, Robert
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Self-Assembly of a Structurally Defined Chiro-Optical Peptide-Oligothiophene Hybrid Material2018Inngår i: ACS OMEGA, ISSN 2470-1343, Vol. 3, nr 11, s. 15066-15075Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conducting polymers are routinely used in optoelectronic biomaterials, but large polymer polydispersity and poor aqueous compatibility complicate integration with biomolecular templates and development of discrete and defined supramolecular complexes. Herein, we report on a chiro-optical hybrid material generated by the self-assembly of an anionic peptide and a chemically defined cationic pentameric thiophene in aqueous environment. The peptide acts as a stereochemical template for the thiophene and adopts an a-helical conformation upon association, inducing optical activity in the thiophene r-n * transition region. Theoretical calculations confirm the experimentally observed induced structural changes and indicate the importance of electrostatic interactions in the complex. The association process is also probed at the substrate-solvent interface using peptide-functionalized gold nanoparticles, indicating that the peptide can also act as a scaffold when immobilized, resulting in structurally well-defined supramolecular complexes. The hybrid complex could rapidly be assembled, and the kinetics of the formation could be monitored by utilizing the local surface plasmon resonance originating from the gold nanoparticles. We foresee that these findings will aid in designing novel hybrid materials and provide a possible route for the development of functional optoelectronic interfaces for both biomaterials and energy harvesting applications.

  • 291.
    Rönnby, Karl
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    A computational study on indium nitride ALD precursors and surface chemical mechanism2018Independent thesis Advanced level (degree of Master (Two Years)), 40 poäng / 60 hpOppgave
    Abstract [en]

    Indium nitride has many applications as a semiconductor. High quality films of indium nitride can be grown using Chemical Vapour Deposition (CVD) and Atomic Layer Deposition (ALD), but the availability of precursors and knowledge of the underlaying chemical reactions is limited. In this study the gas phase decomposition of a new indium precursor, N,N-dimethyl-N',N''-diisopropylguanidinate, has been investigated by quantum chemical methods for use in both CVD and ALD of indium nitride. The computations showed significant decomposition at around 250°C, 3 mbar indicating that the precursor is unstable at ALD conditions. A computational study of the surface chemical mechanism of the adsorption of trimethylindium and ammonia on indium nitride was also performed as a method development for other precursor surface mechanism studies. The results show, in accordance with experimental data, that the low reactivity of ammonia is a limiting factor in thermal ALD growth of indium nitride with trimethylindium and ammonia.

  • 292.
    Rönnby, Karl
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Quantum Chemical Feasibility Study of Methylamines as Nitrogen Precursors in Chemical Vapor Deposition2015Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    The possibility of using methylamines instead of ammonia as a nitrogen precursor for the CVD of nitrides is studied using quantum chemical computations of reaction energies: reaction electronic energy (Δ𝑟𝐸𝑒𝑙𝑒𝑐) reaction enthalpy (Δ𝑟𝐻) and reaction free energy (Δ𝑟𝐺). The reaction energies were calculated for three types of reactions: Uni- and bimolecular decomposition to more reactive nitrogen species, adduct forming with trimethylgallium (TMG) and trimethylaluminum (TMA) followed by a release of methane or ethane and surface adsorption to gallium nitride for both the unreacted ammonia or methylamines or the decomposition products. The calculations for the reaction entropy and free energy were made at both STP and CVD conditions (300°C-1300°C and 50 mbar). The ab inito Gaussian 4 (G4) theory were used for the calculations of the decomposition and adduct reactions while the surface adsorptions were calculated using the Density Functional Theory method B3LYP. From the reactions energies it can be concluded that the decomposition was facilitated by the increasing number of methyl groups on the nitrogen. The adducts with mono- and dimethylamine were more favorable than ammonia and trimethylamine. 𝑁𝐻2 was found to be most readily to adsorb to 𝐺𝑎𝑁 while the undecomposed ammonia and methylamines was not willingly to adsorb.

  • 293.
    Rönnby, Karl
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Buttera, Sydney C.
    Carleton Univ, Canada.
    Rouf, Polla
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Barry, Sean T.
    Carleton Univ, Canada.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Methylamines as Nitrogen Precursors in Chemical Vapor Deposition of Gallium Nitride2019Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 123, nr 11, s. 6701-6710Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chemical vapor deposition (CVD) is one of the most important techniques for depositing thin films of the group 13 nitrides (13-Ns), AIN, GaN, InN, and their alloys, for electronic device applications. The standard CVD chemistry for 13-Ns uses ammonia as the nitrogen precursor; however, this gives an inefficient CVD chemistry, forcing N/13 ratios of 100/1 or more. Here, we investigate the hypothesis that replacing the N-H bonds in ammonia with weaker N-C bonds in methylamines will permit better CVD chemistry, allowing lower CVD temperatures and an improved N/13 ratio. Quantum chemical computations show that while the methylamines have a more reactive gas-phase chemistry, ammonia has a more reactive surface chemistry. CVD experiments using methylamines failed to deposit a continuous film, while instead micrometer-sized gallium droplets were deposited. This study shows that the nitrogen surface chemistry is most likely more important to be considered than the gas-phase chemistry when searching for better nitrogen precursors for 13-N CVD.

    Fulltekst tilgjengelig fra 2020-02-28 08:58
  • 294.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Polymorphic protein aggregation in tauopathies2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease(s) comprises one of the most common and costly neurodegenerative diseases. With a larger population and an increasing life expectancy, amyloid diseases (with age as one of the most prominent risk factors) will generate an even larger burden on healthcare. We know that protein misfolding is involved in the disease process but lack a complete understanding of the mechanism behind these diseases, both the sporadic and hereditary variants. It is not always known whether it is a gain-of-toxic function or loss‐of‐function that causes the neurodegeneration. To determine the correct diagnosis is a major challenge. If diagnosed, only a few amyloid diseases can be treated today.

    Amyloids are highly ordered filamentous protein aggregates with a β‐sheet structure. From identical or similar amino acid sequences, a large variety of structures can be formed by different secondary and tertiary structures and by different packing of the individual filaments. This is known as fibril polymorphism.

    This work focuses on characterization on two proteins involved in Alzheimer’s disease and other neurodegenerative diseases, namely Amyloid‐β (Aβ) and microtubule associated protein tau (tau). In order to investigate the properties of these proteins in vitro it is important to have protocols for production of recombinant protein that enables characterization of these aggregation prone proteins. We present protocols for recombinant expression, purification and non‐denaturing fibrillation assays used in our lab to produce and analyze Aβ, tau and the prion protein.

    Development of new ligands for characterization of fibrils is an important way of investigating different fibrillary structures and characterizing and distinguishing between the different polymorphs of aggregates. We showed that the central benzene ring of the amyloid ligand X‐34 can be exchanged for other heterocyclic motifs and still retain targeting of the “Congo red” binding site. The compounds do not compete with the Pittsburgh compound B (PiB) binding site on recombinant Aβ fibrils.

    We also characterized tau fibrils formed from seeding with tau aggregates from patients diagnosed with different neurodegenerative tauopathies. We use aggregation kinetics to test the seeding activity on two different sequence isoforms of tau, 0N3R and 0N4R. Fibrillation kinetics, an array of recently developed ligands (including the X‐34 analogs) and electron microscopy were used to characterize different polymorphs of the tau aggregates formed by seeded templating from patient derived seeds. Our data showed that brains contain seeds with different morphologies even with in patients diagnosed with the same disease.

    Investigations of the rare tau mutant G273R found in a patient with a presumed tauopathy also highlights the problem with proper diagnostics. Our results reveal that in vitro this mutation change the binding properties of 0N4R tau to the cytoskeletal proteins microtubule and F‐actin. Furthermore, we could show that when seeded, the fibril formation seeding activity followed a sequence similarity dependent manner. In fibrils formed during heparin-induced aggregation we can be distinguished between wild type and mutant tau as they form fibrils with different thickness. Our in vitro biophysical data support that the G237R mutant is causing a 4R tauopathy.

    The work in this thesis increase our knowledge in the field of tau aggregation and tau fibril polymorphism.

    Delarbeid
    1. Purification and Fibrillation of Recombinant Human Amyloid-ß, Prion Protein, and Tau Under Native Conditions
    Åpne denne publikasjonen i ny fane eller vindu >>Purification and Fibrillation of Recombinant Human Amyloid-ß, Prion Protein, and Tau Under Native Conditions
    2018 (engelsk)Inngår i: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, s. 147-166Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Protein misfolding, aggregation, and amyloid formation is involved in a large number of diseases. Recombinantly expressed proteins to study the amyloid fibril formation process are important for mechanistic studies. We here report protocols for production, purification, and fibrillation of three different proteins commonly found in cerebral amyloid; Aß and Tau found in Alzheimers disease, Chronic traumatic brain injury, Corticobasal degeneration, and Progressive Supranuclear Palsy and human prion protein found in Creutzfeldt-Jakobs disease. The three protocols have in common that the protein is in a pH-neutral phosphate saline buffer during fibrillation to mimic their endogenous near physiological environment.

    sted, utgiver, år, opplag, sider
    Humana Press, 2018
    Serie
    Methods in Molecular Biology, E-ISSN 1940-6029 ; 1779
    Emneord
    Amyloid; Aß; Fibrillation; Neurodegenerative disease; Prion protein; Purification; Recombinant; Tau
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-152517 (URN)10.1007/978-1-4939-7816-8_10 (DOI)29886532 (PubMedID)9781493978151 (ISBN)9781493978168 (ISBN)
    Tilgjengelig fra: 2019-03-28 Laget: 2019-03-28 Sist oppdatert: 2019-11-08
    2. Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues
    Åpne denne publikasjonen i ny fane eller vindu >>Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues
    Vise andre…
    2018 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, nr 28, s. 7210-7216Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We revisited the Congo red analogue 2,5-bis(4-hydroxy-3-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimers disease (AD) pathology comprising A beta and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of A beta 1-42 (13-300nmK(d)) and Tau (16-200nmK(d)) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant A beta 1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for A pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of A fibrils.

    sted, utgiver, år, opplag, sider
    WILEY-V C H VERLAG GMBH, 2018
    Emneord
    Alzheimers disease; amyloid ligands; dyes/pigments; fluorescence; microscopy
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-148653 (URN)10.1002/chem.201800501 (DOI)000434074800013 ()29543355 (PubMedID)
    Merknad

    Funding Agencies|China Scholarship Council; Swedish Research Council [2015-04521]; Goran Gustafsson Foundation; Swedish Alzheimer Foundation; Swedish Brain foundation; Linkoping University (LiU-Neuro); NIH/NINDS [R21 NS080576]

    Tilgjengelig fra: 2018-06-18 Laget: 2018-06-18 Sist oppdatert: 2019-11-08
  • 295.
    Sandberg, Alexander
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Purification and Fibrillation of Recombinant Human Amyloid-ß, Prion Protein, and Tau Under Native Conditions2018Inngår i: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, s. 147-166Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Protein misfolding, aggregation, and amyloid formation is involved in a large number of diseases. Recombinantly expressed proteins to study the amyloid fibril formation process are important for mechanistic studies. We here report protocols for production, purification, and fibrillation of three different proteins commonly found in cerebral amyloid; Aß and Tau found in Alzheimers disease, Chronic traumatic brain injury, Corticobasal degeneration, and Progressive Supranuclear Palsy and human prion protein found in Creutzfeldt-Jakobs disease. The three protocols have in common that the protein is in a pH-neutral phosphate saline buffer during fibrillation to mimic their endogenous near physiological environment.

  • 296.
    Sandgren, Veronica
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Belda, Oscar
    Medivir AB, Huddinge, Sweden.
    Kvarnström, Ingemar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Lindberg, Jimmy
    Medivir AB, Huddinge, Sweden.
    Samuelsson, Bertil
    Medivir AB, Huddinge, Sweden.
    Dahlgren, Anders
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Design and Synthesis of Novel Arylketo-containing P1-P3 Linked Macro-cyclic BACE-1 Inhibitors2015Inngår i: Open Medicinal Chemistry Journal, ISSN 1874-1045, Vol. 9, s. 13-26Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A series of arylketo-containing P1-P3 linked macrocyclic BACE-1 inhibitors were designed, synthesized, and compared with compounds with a previously known and extensively studied corresponding P2 isophthalamide moiety with the aim to improve on permeability whilst retaining the enzyme- and cell-based activities. Several inhibitors displayed substantial increases in Caco-2 cell-based permeability compared to earlier synthesized inhibitors and notably also with retained activities, showing that this approach might yield BACE-1 inhibitors with improved properties.

  • 297.
    Sandin, Linnea
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Bergkvist, Liza
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Nath, Sangeeta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kielkopf, Claudia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Helmfors, Linda
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden / UCL Institute of Neurology, London, UK.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.
    Li, Hongyun
    Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
    Nilsberth, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Garner, Brett
    Illawarra Health and Medical Research Institute, University of Wollongong, Australia / School of Biological Sciences, University of Wollongong, Australia.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster2016Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 283, nr 19, s. 3508-3522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.

  • 298.
    Schuetz, Anne K.
    et al.
    Swiss Fed Inst Technol, Switzerland.
    Hornemann, Simone
    Univ Zurich, Switzerland.
    Waelti, Marielle A.
    Swiss Fed Inst Technol, Switzerland.
    Greuter, Ladina
    Univ Zurich, Switzerland.
    Tiberi, Cinzia
    Univ Zurich, Switzerland.
    Cadalbert, Riccardo
    Swiss Fed Inst Technol, Switzerland.
    Gantner, Matthias
    Swiss Fed Inst Technol, Switzerland.
    Riek, Roland
    Swiss Fed Inst Technol, Switzerland.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Boeckmann, Anja
    Univ Lyon 1, France.
    Aguzzi, Adriano
    Univ Zurich, Switzerland.
    Meier, Beat H.
    Swiss Fed Inst Technol, Switzerland.
    Binding of Polythiophenes to Amyloids: Structural Mapping of the Pharmacophore2018Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 9, nr 3, s. 475-481Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. 560 We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene.

  • 299.
    Schultz, Sebastian
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Torstensdotter Westermark, Gunilla
    Uppsala University.
    Drosophila Melanogaster as a Model System for Studies of Islet Amyloid Polypeptide Aggregation2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Recent research supports that aggregation of islet amyloid polypeptide (IAPP) leads to cell death and this makes islet amyloid a plausible cause for the reduction of beta cell mass, demonstrated in patients with type 2 diabetes. IAPP is produced by the beta cells as a prohormone, and proIAPP is processed into IAPP by the prohormone convertases PC1/3 and PC2 in the secretory granules. Little is known about the pathogenesis for islet amyloid and which intracellular mechanisms are involved in amyloidogenesis and induction of cell death.

    Methodology/Principal Findings: We have established expression of human proIAPP (hproIAPP), human IAPP (hIAPP) and the non-amyloidogenic mouse IAPP (mIAPP) in Drosophila melanogaster, and compared survival of flies with the expression driven to different cell populations. Only flies expressing hproIAPP in neurons driven by the Gal4 driver elavC(155,Gal4) showed a reduction in lifespan whereas neither expression of hIAPP or mIAPP influenced survival. Both hIAPP and hproIAPP expression caused formation of aggregates in CNS and fat body region, and these aggregates were both stained by the dyes Congo red and pFTAA, both known to detect amyloid. Also, the morphology of the highly organized protein granules that developed in the fat body of the head in hIAPP and hproIAPP expressing flies was characterized, and determined to consist of 15.8 nm thick pentagonal rod-like structures.

    Conclusions/Significance: These findings point to a potential for Drosophila melanogaster to serve as a model system for studies of hproIAPP and hIAPP expression with subsequent aggregation and developed pathology.

  • 300.
    Sekijima, Yoshiki
    et al.
    Shinshu University,Matsumoto, Japan.
    Campos, Raul Ivan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Yoshinaga, Tsuneaki
    Shinshu University, Matsumoto, Japan.
    Nagamatsu, Kiyoshiro
    Shinshu University, Matsumoto, Japan.
    Yazaki, Masahide
    Shinshu University,Matsumoto, Japan.
    Kametani, Fuyuki
    Tokyo Metropolitan Org Medical Research, Japan.
    Ikeda, Shu-ichi
    Shinshu University, Matsumoto, Japan.
    Pathological, biochemical, and biophysical characteristics of the transthyretin variant Y114H (p.Y134H) explain its very mild clinical phenotype2015Inngår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 20, nr 4, s. 372-379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transthyretin (TTR) is a homotetrameric protein that must misfold in order to form amyloid fibrils. Misfolding includes rate limiting tetramer dissociation, followed by fast tertiary structural changes of the monomer that enable aggregation. Hereditary ATTR amyloidosis is an autosomal dominant genetic disorder with systemic deposition of amyloid fibrils induced by TTR gene mutation. We identified a rare Y114H (p.Y134H) TTR variant in a Japanese patient presenting with late-onset, very mild clinical course. The patient had an extremely low serum variant TTR concentration (18% of total TTR), whereas the composition of variant TTR was 55% in amyloid fibrils in tenosynovial tissues obtained at carpal tunnel release surgery. The amyloid fibril deposits in the ATTR Y114H patient had an altered structure compared with that in wild-type ATTR patients, as determined by luminescent conjugated poly/oligo-thiophene fluorescence spectroscopy. Biophysical studies using recombinant protein showed that Y114H TTR was markedly destabilized both thermodynamically and kinetically and was highly amyloidogenic in vitro. These data suggest that extremely low serum variant Y114H TTR concentration, probably due to endoplasmic reticulum-associated degradation of unstable variant TTR protein, protected this patient from severe amyloidosis, as self-assembly of the amyloidogenic intermediate is a concentration-dependent process.

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