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  • 201.
    Liu, Yuan
    et al.
    Beijing Univ Chem Technol, Peoples R China; Univ Nebraska, NE 68588 USA.
    Huang, Yingying
    Chinese Acad Sci, Peoples R China; Dalian Univ Technol, Peoples R China.
    Zhu, Chongqin
    Univ Nebraska, NE 68588 USA; Univ Penn, PA 19104 USA; Univ Penn, PA 19104 USA.
    Li, Hui
    Beijing Univ Chem Technol, Peoples R China.
    Zhao, Jijun
    Dalian Univ Technol, Peoples R China.
    Wang, Lu
    Univ Sci and Technol China, Peoples R China.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Francisco, Joseph S.
    Univ Nebraska, NE 68588 USA; Univ Penn, PA 19104 USA; Univ Penn, PA 19104 USA.
    Zeng, Xiao Cheng
    Beijing Univ Chem Technol, Peoples R China; Univ Nebraska, NE 68588 USA.
    An ultralow-density porous ice with the largest internal cavity identified in the water phase diagram2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 26, p. 12684-12691Article in journal (Refereed)
    Abstract [en]

    The recent back-to-back findings of low-density porous ice XVI and XVII have rekindled the century-old field of the solid-state physics and chemistry of water. Experimentally, both ice XVI and XVII crystals can be produced by extracting guest atoms or molecules enclosed in the cavities of preformed ice clathrate hydrates. Herein, we examine more than 200 hypothetical low-density porous ices whose structures were generated according to a database of zeolite structures. Hitherto unreported porous EMT ice, named according to zeolite nomenclature, is identified to have an extremely low density of 0.5 g/cm(3) and the largest internal cavity (7.88 angstrom in average radius). The EMT ice can be viewed as dumbbell-shaped motifs in a hexagonal close-packed structure. Our first-principles computations and molecular dynamics simulations confirm that the EMT ice is stable under negative pressures and exhibits higher thermal stability than other ultralow-density ices. If all cavities are fully occupied by hydrogen molecules, the EMT ice hydrate can easily outperform the record hydrogen storage capacity of 5.3 wt % achieved with sII hydrogen hydrate. Most importantly, in the reconstructed temperature-pressure (T-P) phase diagram of water, the EMT ice is located at deeply negative pressure regions below ice XVI and at higher temperature regions next to FAU. Last, the phonon spectra of empty-sII, FAU, EMT, and other zeolite-like ice structures are computed by using the dispersion corrected vdW-DF2 functional. Compared with those of ice XI (0.93 g/cm(3)), both the bending and stretching vibrational modes of the EMT ice are blue-shifted due to their weaker hydrogen bonds.

  • 202.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    C-13 Chemical Shift in Natural Gas Hydrates from First-Principles Solid-State NMR Calculations2016In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 120, no 2, p. 1130-1136Article in journal (Refereed)
    Abstract [en]

    Natural gas hydrates (NGHs) are of interest both as a prospective energy resource and for possible technological applications. C-13 NMR technology is a powerful tool to characterize NGHs, and in this work, the trends and origins of C-13 NMR chemical shifts of hydrocarbon molecules in NGHs from quantum-chemical first-principles calculations on solid state phases are presented. The chemical shift is found to decrease as the size of the water cavities increases for single occupancy NGHs, and to increase as the amount of CH4 increases for the multioccupancy cases. In most cases, the chemical shift of NGHs monotonically increases as the external pressure increases. Furthermore, the chemical shift can be mainly attributed to the host-guest interaction together with a small contributions from water molecules for tight environments and mainly depends on host-guest interaction for loose environments. The theoretical results provide useful information for identification of the types of clathrate phases and guest molecules included in NGH samples taken from natural sites.

  • 203.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    C-C Stretching Raman Spectra and Stabilities of Hydrocarbon Molecules in Natural Gas Hydrates: A Quantum Chemical Study2014In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 118, no 49, p. 11641-11651Article in journal (Refereed)
    Abstract [en]

    The presence of specific hydrocarbon gas molecules in various types of water cavities in natural gas hydrates (NGHs) are governed by the relative stabilities of these encapsulated guest molecule-water cavity combinations. Using molecular quantum chemical dispersion-corrected hybrid density functional computations, the interaction (Delta E(host-)guest) and cohesive energies (Delta E-coh), enthalpies, and Gibbs free energies for the complexes of host water cages and hydrocarbon guest molecules are calculated at the pi B97X-D/6-311++G(2d,2p) level of theory. The zero-point energy effect of ?Ehost-guest and ?Ecoh is found to be quite substantial. The energetically optimal host-guest combinations for seven hydrocarbon gas molecules (CH4, C2H6, C3H6, C3H8, C4H8, i-C4H10, and n-C4H10) and various water cavities (D, ID, T, P, H, and I) in NGHs are found to be CH4@D, C2H6@T, C3H6@T, C3H8@T, C4H8@T/P/H, i-C4H10@H, and n-C4H10@H, as the largest cohesive energy magnitudes will be obtained with these host-guest combinations. The stabilities of various water cavities enclosing hydrocarbon molecules are evaluated from the computed cohesive Gibbs free energies: CH4 prefers to be trapped in a ID cage; C2H6 prefer T cages; C3H6 and C3H8 prefer T and H cages; C4H8 and i-C4H10 prefer H cages; and n-C4H10 prefer I cages. The vibrational frequencies and Raman intensities of the C-C stretching vibrational modes for these seven hydrocarbon molecules enclosed in each water cavity are computed. A blue shift results after the guest molecule is trapped from gas phase into various water cages due to the host-guest interactions between the water cage and hydrocarbon molecule. The frequency shifts to the red as the radius of water cages increases. The model calculations support the view that C-C stretching vibrations of hydrocarbon molecules in the water cavities can be used as a tool to identify the types of crystal phases and guest molecules in NGHs.

  • 204.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Not Found:Linkoping Univ, Dept Chem, IFM, SE-58183 Linkoping, Sweden.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    CH-Stretching Vibrational Trends in Natural Gas Hydrates Studied by Quantum-Chemical Computations2015In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, no 30, p. 17084-17091Article in journal (Refereed)
    Abstract [en]

    Vibrational Raman spectrosopy of hydrocarbon CH-stretching vibrations is often-used to study natural gas, hydrates., In this work, CH-stretching vibrational, Raman spectra of hydrocarbon molectles (CH4, C2H6, C(3)H6, C3H8, C4H8, i-C4H10, and n-C4H10) encapsulated in the water cages (D, ID, T, P, H, and I) of the SI, sII, sH, and sK crystal phases. are derived from quantum-chemical computations at the omega B97X-D/6-311++G(24,2p) level of theory. The trends of CH-stretching vibrational frequencies Of hydrocarbon Molecules in natural gas hydrates are found to follow the prediction by the loose cage tight cage model: as the size of Water cavity increases, the CH frequencies will first decrease and: then increase until equal to-that in the gas phase. In the "tight cage" situation, the frequency will be greater than in the gas phase; in the "loose cage" situation, the frequency will be smaller or asymptotic to that in the gas phase. Furthermore, the OH-stretching frequencies are sensitive to the H-bond configuration, and the varying strengths of H-bonds for different configurations are reflected by,the frequency distribution in the corresponding subspectra.

  • 205.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Beijing Univ Chem Technol, Peoples R China.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Clathrate ice sL: a new crystalline phase of ice with ultralow density predicted by first-principles phase diagram computations2018In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 12, p. 8333-8340Article in journal (Refereed)
    Abstract [en]

    In contrast to the rich knowledge of water and 17 experimentally confirmed crystalline phases of solid water under positive pressures, water under negative pressure has been poorly explored. In this study, a new crystalline phase of ice with ultralow density (0.6 g cm(-3)), named clathrate ice sL, is constructed by nano water cage clusters, and it is predicted to be stable under a lower negative pressure than the experimentally confirmed sII phase by first-principles phase diagram computations, thereby extending the phase diagram of water to negative pressure regions below -5170 bar at 0 K and below -4761 bar at 300 K. In addition, according to our theoretical prediction, the optimal hydrogen storage mass density in the new clathrate ice sL is 7.7 wt% (larger than the 2017 DOE target of 5.5 wt%), which would set a new record of hydrogen storage capacity in clathrate hydrates. The finding of clathrate ice sL not only proposes a new type of crystalline ice under negative pressure but also explores the potential applications of the ultralow density ice phases while extending the water phase diagram and enriching the knowledge of people about water.

  • 206.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Fingerprints in IR OH vibrational spectra of H2O clusters from different H-bond conformations by means of quantum-chemical computations2014In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 20, no 6, p. 2281-Article in journal (Refereed)
    Abstract [en]

    The thermodynamic stabilities and IR spectra of the three water clusters (H2O)(20), (H2O)(54,), and (H2O)(100) are studied by quantum-chemical computations. After full optimization of the (H2O)(20,54,100) structures using the hybrid density functional B3LYP together with the 6-31+G(d,p) basis set, the electronic energies, zero-point energies, internal energies, enthalpies, entropies, and Gibbs free energies of the water clusters at 298 K are investigated. The OH stretching vibrational IR spectra of (H2O)(20,54,100) are simulated and split into sub-spectra for different H-bond groups depending on the conformations of the hydrogen bonds. From the computed spectra the different spectroscopic fingerprint features of water molecules in different H-bond conformations in the water clusters are inferred.

  • 207.
    Liu, Yuan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Raman and IR Spectra of Ice Ih and Ice XI with an Assessment of DFT Methods2016In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, no 42, p. 11043-11051Article in journal (Refereed)
    Abstract [en]

    IR and Raman spectroscopic technology can be directly used to identify the occurrence of ferroelectric ice XI in laboratory or extraterrestrial settings. The performance of 16 different DFT methods applied on the ice Ih, VIII, IX, and XI crystal phases is evaluated. Based on a selected DFT computational scheme, the IR and Raman spectra of ice Ih and XI are derived and compared. When the spectra, both IR and Raman, of ice Ih and ice XI are compared, the librational vibrations are found to be the most affected by the proton ordering. The spectroscopic fingerprint of ice XI can be used to distinguish ferroelectric ice XI from ice Ih in the universe. Furthermore, the existence of only one kind of H-bond in ice Ih is demonstrated from the overlapping subspectra for different types of H-bonded pair configurations in 16 isomers of ice Ih, which provides an illustration to the historic debate on whether one or two kinds of H-bonds existed in ice.

  • 208.
    Lloyd Spetz, Anita
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Pearce, Ruth
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Hedin, Linnea
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Khranovskyy, Volodymyr
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, The Institute of Technology.
    Käll, Per-Olov
    Linköping University, Department of Physics, Chemistry and Biology, Physical Chemistry. Linköping University, The Institute of Technology.
    Yakimova, Rositsa
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    New transducer material concepts for biosensors and surface functionalization2009In: Smart Sensors, Actuators,and MEMS IV / [ed] Ulrich Schmid, Carles Cané, Herbert Shea, Bellingham, WA United States: SPIE - International Society for Optical Engineering, 2009, Vol. 7362, p. 736206-Conference paper (Refereed)
    Abstract [en]

    Wide bandgap materials like SiC, ZnO, AlN form a strong platform as transducers for biosensors realized as e.g. ISFET (ion selective field effect transistor) devices or resonators. We have taken two main steps towards a multifunctional biosensor transducer. First we have successfully functionalized ZnO and SiC surfaces with e.g. APTES. For example ZnO is interesting since it may be functionalized with biomolecules without any oxidation of the surface and several sensing principles are possible. Second, ISFET devises with a porous metal gate as a semi-reference electrode are being developed. Nitric oxide, NO, is a gas which participates in the metabolism. Resistivity changes in Ga doped ZnO was demonstrated as promising for NO sensing also in humid atmosphere, in order to simulate breath.

  • 209.
    Loffler, S.
    et al.
    Karolinska Institute, Sweden.
    Melican, K.
    Karolinska Institute, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Richter-Dahlfors, A.
    Karolinska Institute, Sweden.
    Organic bioelectronics in medicine2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 1, p. 24-36Article in journal (Refereed)
    Abstract [en]

    A major challenge in the growing field of bioelectronic medicine is the development of tissue interface technologies promoting device integration with biological tissues. Materials based on organic bioelectronics show great promise due to a unique combination of electronic and ionic conductivity properties. In this review, we outline exciting developments in the field of organic bioelectronics and demonstrate the medical importance of these active, electronically controllable materials. Importantly, organic bioelectronics offer a means to control cell-surface attachment as required for many device-tissue applications. Experiments have shown that cells readily attach and proliferate on reduced but not oxidized organic bioelectronic materials. In another application, the active properties of organic bioelectronics were used to develop electronically triggered systems for drug release. After incorporating drugs by advanced loading strategies, small compound drugs were released upon electrochemical trigger, independent of charge. Another type of delivery device was used to achieve well-controlled, spatiotemporal delivery of cationic drugs. Via electrophoretic transport within a polymer, cations were delivered with single-cell precision. Finally, organic bioelectronic materials are commonly used as electrode coatings improving the electrical properties of recording and stimulation electrodes. Because such coatings drastically reduce the electrode impedance, smaller electrodes with improved signal-to-noise ratio can be fabricated. Thus, rapid technological advancement combined with the creation of tiny electronic devices reacting to changes in the tissue environment helps to promote the transition from standard pharmaceutical therapy to treatment based on electroceuticals. Moreover, the widening repertoire of organic bioelectronics will expand the options for true biological interfaces, providing the basis for personalized bioelectronic medicine.

  • 210.
    Loffler, Susanne
    et al.
    Karolinska Inst, Sweden.
    Antypas, Hails
    Karolinska Inst, Sweden.
    Choong, Ferdinand X.
    Karolinska Inst, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Richter-Dahlfors, Agneta
    Karolinska Inst, Sweden.
    Conjugated Oligo- and Polymers for Bacterial Sensing2019In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 7, article id 265Article, review/survey (Refereed)
    Abstract [en]

    Fast and accurate detection of bacteria and differentiation between pathogenic and commensal colonization are important keys in preventing the emergence and spread of bacterial resistance toward antibiotics. As bacteria undergo major lifestyle changes during colonization, bacterial sensing needs to be achieved on different levels. In this review, we describe how conjugated oligo- and polymers are used to detect bacterial colonization. We summarize how oligothiophene derivatives have been tailor-made for detection of biopolymers produced by a wide range of bacteria upon entering the biofilm lifestyle. We further describe how these findings are translated into diagnostic approaches for biofilm-related infections. Collectively, this provides an overview on how synthetic biorecognition elements can be used to produce fast and easy diagnostic tools and new methods for infection control.

  • 211.
    Lundberg, Alexander
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Studying the Oligomerization of the Kinase Domain of Ephrin type-B Receptor 2 Using Analytical Ultracentrifugation and Development of a Program for Analysis of Acquired Data2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Ephrin type-B receptor 2 (EphB2) is a receptor tyrosine kinase which phosphorylates proteins and thereby regulates cell migration, vascular development, axon guidance synaptic plasticity, and formation of borders between tissues. It has been seen overexpressed in several cancers, which make it an interesting protein to study. In this thesis EphB2 kinase domain (KD) and juxtamembrane segment with kinase domain (JMS-KD) have been expressed, purified and studied using analytical ultracentrifugation to evaluate the oligomerisation of the KD and how the double mutation S677/680A affects this. A program for data analysis have been written and used for analysis of the acquired data. The values of the dissociation constant were 2.94±1.04 mM for KD wild type and 3.46±2.26 mM for JMS-KD wild type have been calculated. Due to varied problems with the measurements no data was acquired on the double mutant, and not enough data was gained to draw any conclusions. Additional experiments will be needed to understand the oligomerisation of this intriguing protein.

  • 212.
    Lundberg, Rickard
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Rättsmedicinalverket.
    Ethanol, ethyl glucuronide, and ethyl sulfate kinetics after multiple ethanol intakes: A study of ethanol consumption to better determine the latest intake of alcoholin hip flask defence cases2018Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The hip-flask defence is a common claim in drunkdrinking cases. In Sweden and Norway two different models are used to determinethese cases. In Sweden one blood and two urine samples taken 60 minutes apartare used for analysis. In Norway two blood samples taken 30 minutes apart areused. Sweden focuses on the rise or fall of alcohol concentration in urine(UAC), and the ratio between UAC and blood alcohol concentrations (BAC). Norwayfocuses on the rise or fall of the alcohol metabolite ethylglucuronide (EtG) and the ratio between BAC and EtG. The aim of this study wasto test the models for multiple intakes and with different alcoholic beverages.Thirtyfive participants ingested two doses, first0.51 g/kg of beer and later either 0.25, 0.51 or 0.85 g/kg of beer, wine orvodka. Blood and urine samples were obtained before and after alcoholingestion. Alcohol was measured by GC-HS, and the alcohol metabolite byUPLC-MS/MS. The results showed that there are kineticdifferences between single and repeated intakes, that there are no significantdifferences in kinetics from different alcoholic beverages and thatthe Norwegian model appears to be the stronger one in hip-flask determination.

  • 213.
    Lundberg, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry.
    Validation of Biomarkers for the Revision of the CEN/TR 15522-2:2012 Method: A Statistical Study of Sampling, Discriminating Powers and Weathering of new Biomarkers for Comparative Analysis of Lighter Oils2019Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The revision of the CEN/TR 15522-2:2012 methodology contains new biomarkers to facilitate forensic fingerprinting of the variety of oil types that can be a part of different crimes and the purpose of this project is to validate the biomarkers of the new methodology. Biomarkers were validated by examining corresponding diagnostic ratios compatibility with the internationally used sampling cloth, discriminating power, correlation and simulated weathering sensibility through GC-SIM-MS analysis followed by statistical evaluation with t-tests, diagnostic power, Pearson correlation matrices and MS-PW plots respectively. Results based on most of the diagnostic ratios showed good compatibility with the internationally used sampling cloth, expected patterns of biodegradation and photo-oxidation except for observed photo-oxidation of hydro PAHs and that normative ratios and informative ratios with high diagnostic powers, but with strong correlations for some of the tested ratios, could be identified in diesel oils. Due to delimitations however such as the limited number of oils with similar origins that were analyzed the results should be regarded as guidelines that can be expanded.

  • 214.
    Lunden, Hampus
    et al.
    Swedish Def Res Agcy FOI, Sensor & EW Syst, Linkoping, Sweden.
    Liotta, A.
    University of Lyon 1, France.
    Chateau, D.
    University of Lyon 1, France.
    Lerouge, F.
    University of Lyon 1, France.
    Chaput, F.
    University of Lyon 1, France.
    Parola, S.
    University of Lyon 1, France.
    Brannlund, C.
    Swedish Def Research Agency FOI, Sensor and EW Syst, SE-58111 Linkoping, Sweden.
    Ghadyani, Z.
    Norwegian University of Science and Technology, Norway.
    Kildemo, M.
    Norwegian University of Science and Technology, Norway.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technology, Norway.
    Lopes, C.
    Swedish Def Research Agency FOI, Sensor and EW Syst, SE-58111 Linkoping, Sweden.
    Dispersion and self-orientation of gold nanoparticles in sol-gel hybrid silica - optical transmission properties2015In: Journal of Materials Chemistry C, ISSN 2050-7526, E-ISSN 2050-7534, Vol. 3, no 5, p. 1026-1034Article in journal (Refereed)
    Abstract [en]

    Silica-based hybrid materials doped with gold nanoparticles (AuNPs) of different shapes were prepared with an adapted sol-gel technology (using MTEOS) and polished to high optical quality. Both spherical (23 and 45 nm in diameter) and bipyramidal (36, 50 and 78 nm in length) AuNPs were prepared and used as dopants. The AuNPs were functionalized with a novel silicone polymer for compatibilization with the sol-gel medium. The glass materials showed well defined localized surface plasmon resonance (SPR) absorbance from the visible to NIR. No redshifts in the spectra, due to the increase in doping concentration, were observed in the glasses, proving that no or very small SPR coupling effects occur. Spectroscopic Muller Matrix Ellipsometry showed that the shorter bipyramidal AuNPs (36 and 50 nm in length) have a clear preferred orientation in the MTEOS matrix, i.e. a tendency to be oriented with their long axis in the plane parallel to the glass surfaces. Dispersions of AuNPs have proven to be good optical power limiters that depend on particle size and geometry. The solid-state glass materials showed good optical power limiting at 532 nm for nanosecond pulses, which did not depend on the size or geometry of the AuNPs. In contrast to the observation at 532 nm, at 600 nm no optical limiting effect was observed. In these solids, as for dispersions of AuNPs, the optical limiting response is caused by scattering.

  • 215.
    Lundin, Daniel
    et al.
    University of Paris 11, France .
    Jensen, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Influence of pulse power amplitude on plasma properties and film deposition in high power pulsed plasma enhanced chemical vapor deposition2014In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 32, no 3Article in journal (Refereed)
    Abstract [en]

    The discharge characteristics in high power pulsed plasma enhanced chemical vapor deposition is studied with the aim to characterize the impact of high power pulses (HiPP). Using a power scheme of combined HiPP and direct current (DC) to ignite the plasma discharge, and adjusting the HiPP/DC time-averaged power ratio while keeping the total power constant, the effect of the high power pulses was isolated from the total power. By monitoring the discharge current along with the optical emission from the plasma, it is found that the amount of available ions increased with increasing HiPP/DC ratio, which indicates a higher plasma density. Using carbon films deposited from acetylene in an argon plasma as model system, a strong increase in deposition rate with higher HiPP/DC is observed. The increased deposition rate is ascribed to a more efficient plasma chemistry generated by the denser plasma.

  • 216.
    Lundén, H.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Optics. Linköping University, Faculty of Science & Engineering. Electrooptical Systems, Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Lopes, Cesar
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
    Liotta, A.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Chateau,, D.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Lerouge,, F.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Chaput,, F.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Désert,, A.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Parola,, S.
    Laboratoire de Chimie, ENS de Lyon, Lyon, France.
    Efficient reverse saturable absorption of sol-gel hybrid plasmonic glasses2017In: Optical materials (Amsterdam), ISSN 0925-3467, E-ISSN 1873-1252, Vol. 69, p. 134-140Article in journal (Refereed)
    Abstract [en]

    Monolithic silica sol-gel glasses doped with platinum(II) acetylide complexes possessing respectively four or six phenylacetylene units (PE2-CH2OH and PE3-CH2OH) in combination with various concentrations of spherical and bipyramidal gold nanoparticles (AuNPs) known to enhance non-linear optical absorption, were prepared and polished to high optical quality. The non-linear absorption of the glasses was measured and compared to glasses doped solely with AuNPs, a platinum(II) acetylide with shorter delocalized structure, or combinations of both. At 532 nm excitation wavelength the chromophore inhibited the non-linear scattering previously found for glasses only doped with AuNPs. The measured non-linear absorption was attributed to reverse saturable absorption from the chromophore, as previously reported for PE2-CH2OH/AuNP glasses. At 600 nm strong nonlinear absorption was observed for the PE3-CH2OH/AuNPs glasses, also attributed to reverse saturable absorption. But contrary to previous findings for PE2-CH2OH/AuNPs, no distinct enhancement of the non-linear absorption for PE3-CH2OH/AuNPs was observed. A numerical population model for PE3-CH2OH was used to give a qualitative explanation of this difference. A stronger linear absorption in PE3-CH2OH would cause the highly absorbing triplet state to populate quicker during the leading edge of the laser pulse and this would in turn reduce the influence from two-photon absorption enhancement from AuNPs.

  • 217.
    Lundén, Hampus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Glimsdal, Eirik
    Norwegian Def Res Estab FFI, Norway; Norwegian Univ Sci and Technol NTNU, Norway.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Norwegian Univ Sci and Technol NTNU, Norway.
    Lopes, Cesar
    Swedish Def Res Agcy, FOI, Linkoping, Sweden.
    How to assess good candidate molecules for self-activated optical power limiting2018In: Optical Engineering: The Journal of SPIE, ISSN 0091-3286, E-ISSN 1560-2303, Vol. 57, no 3, article id 030802Article in journal (Refereed)
    Abstract [en]

    Reverse saturable absorbers have shown great potential to attenuate laser radiation. Good candidate molecules and various particles have successfully been incorporated into different glass matrices, enabling the creation of self-activated filters against damaging laser radiation. Although the performance of such filters has been impressive, work is still ongoing to improve the performance in a wider range of wavelengths and pulse widths. The purpose of this tutorial is, from an optical engineering perspective, to give an understanding of the strengths and weaknesses of this class of smart materials, how relevant photophysical parameters are measured and influence system performance and comment on the pitfalls in experimental evaluation of materials. A numerical population model in combination with simple physical formulas is used to demonstrate system behavior from a performance standpoint. Geometrical reasoning shows the advantage of reverse saturable absorption over nonlinear scattering due to a fraction of scattered light being recollected by imaging system optics. The numerical population model illustrates the importance of the optical power limiting performance during the leading edge of a nanosecond pulse, which is most strongly influenced by changes in the two-photon absorption cross section and the triplet linear absorption cross section for a modeled Pt-acetylide. This tutorial not only targets optical engineers evaluating reverse saturable absorbing materials but also aims to assist researchers with a chemistry background working on optical power limiting materials. We also present photophysical data for a series of coumarins that can be useful for the determination of quantum yields and two-photon cross sections and show examples of characterization of molecules with excited triplet states. (c) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE).

  • 218.
    Löw, Christian
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Quistgaard, Esben M.
    Karolinska Institutet, Stockholm, Sweden.
    Kovermann, Michael
    Martin-Luther-Universität Halle-Wittenberg, Germany .
    Anandapadmanaban, Madhanagopal
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Karolinska Institutet, Stockholm, Sweden.
    Balbach, Jochen
    Martin-Luther-Universität Halle-Wittenberg, Germany .
    Nordlund, Pär
    Karolinska Institute, Sweden; Nanyang Technology University, Singapore .
    Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A2014In: Biological chemistry (Print), ISSN 1431-6730, E-ISSN 1437-4315, Vol. 395, no 7-8, p. 881-889Article in journal (Refereed)
    Abstract [en]

    Protein phosphatase 2A (PP2A) is a highly abundant heterotrimeric Ser/Thr phosphatase involved in the regulation of a variety of signaling pathways. The PP2A phosphatase activator (PTPA) is an ATP-dependent activation chaperone, which plays a key role in the biogenesis of active PP2A. The C-terminal tail of the catalytic subunit of PP2A is highly conserved and can undergo a number of posttranslational modifications that serve to regulate the function of PP2A. Here we have studied structurally the interaction of PTPA with the conserved C-terminal tail of the catalytic subunit carrying different posttranslational modifications. We have identified an additional interaction site for the invariant C-terminal tail of the catalytic subunit on PTPA, which can be modulated via posttranslational modifications. We show that phosphorylation of Tyr307(PP2A-C) or carboxymethylation of Leu309(PP2A-C) abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304(PP2A-C) is of no consequence. We suggest that the invariant C-terminal residues of the catalytic subunit can act as affinity enhancer for different PP2A interaction partners, including PTPA, and a different code of posttranslational modifications can favour interactions to one subunit over others.

  • 219.
    Magnusson, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Poly-and oligothiophenes: Optical probes for multimodal fluorescent assessment of biological processes2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One interesting class of molecules in the research field of imaging biological processes is luminescent conjugated polythiophenes, LCPs. These fluorescent probes have a flexible backbone consisting of repetitive thiophene units. Due to this backbone, the probes possess unique abilities to give rise to different spectral signatures depending on their target and environment. LCPs are a polydispersed material meaning there is an uneven distribution of lengths of the probe. Recently, monodispersed chemically well-defined material denoted luminescent conjugated oligothiophenes, LCOs, with an exact number of repetitive units and distinct sidechain functionalities along the backbone has been developed. LCOs have the advantages of being smaller which leads to higher ability to cross the blood brain barrier. The synthesis of minor chemical alterations is also more simplified due to the well-defined materials.

    During my doctoral studies I have used both LCPs and LCOs to study biological processes such as conformational variation of protein aggregates in prion diseases and cellular uptake in normal cells and cancer cells. The research has generally been based on the probes capability to emit light upon irradiation and the interaction with their targets has mainly been assessed through variations in fluorescence intensity, emission-and excitation profiles and fluorescence lifetime decay. These studies verified the utility of LCPs and LCOs for staining and discrimination of both prion strains and cell phenotypes. The results also demonstrated the pronounced influence minor chemical modifications have on the LCO´s staining capacity.

    List of papers
    1. Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands
    Open this publication in new window or tab >>Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands
    Show others...
    2014 (English)In: Prion, ISSN 1933-6896, E-ISSN 1933-690X, Vol. 8, no 4, p. 319-329Article in journal (Refereed) Published
    Abstract [en]

    The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2014
    National Category
    Chemical Sciences Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-106792 (URN)10.4161/pri.29239 (DOI)000348376000006 ()
    Available from: 2014-05-23 Created: 2014-05-23 Last updated: 2018-04-25Bibliographically approved
    2. Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
    Open this publication in new window or tab >>Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
    Show others...
    2015 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed) Published
    Abstract [en]

    Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

    Place, publisher, year, edition, pages
    Wiley: 12 months, 2015
    Keywords
    Conjugated polyelectrolyte; Fibroblast; Fluorescence; Luminescent conjugated polythiophene; Melanoma; Photoinduced toxicity
    National Category
    Structural Biology Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-115887 (URN)10.1002/cyto.a.22627 (DOI)000349984200009 ()25605326 (PubMedID)2-s2.0-84923259526 (Scopus ID)
    Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2018-09-14
    3. Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives
    Open this publication in new window or tab >>Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives
    Show others...
    2014 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, p. 628-635Article in journal (Refereed) Published
    Abstract [en]

    Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2014
    Keywords
    cancer stem cells; luminescent conjugated oligothiophenes; fluorescent probes
    National Category
    Clinical Medicine Chemical Sciences Medical Biotechnology Computer and Information Sciences
    Identifiers
    urn:nbn:se:liu:diva-109171 (URN)10.1002/cyto.a.22437 (DOI)000338007700010 ()24500794 (PubMedID)
    Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2018-01-11Bibliographically approved
    4. An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells
    Open this publication in new window or tab >>An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells
    Show others...
    2015 (English)In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed) Published
    Abstract [en]

    Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

    Place, publisher, year, edition, pages
    Frontiers Media S.A., 2015
    Keywords
    Oligothiophenes, fluorescence, cells, imaging, imidazole
    National Category
    Clinical Medicine Chemical Sciences Medical Biotechnology
    Identifiers
    urn:nbn:se:liu:diva-121813 (URN)10.3389/fchem.2015.00058 (DOI)000373364600001 ()
    Note

    Vid tiden för disputation förelåg publikationen som manuskript

    Funding agencies:  Swedish Foundation for Strategic Research; GeCONil [POIG.02.03.01-24-099/13]; ERC from the European Research Council

    Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2017-12-01Bibliographically approved
  • 220.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Institute of Automatic Control, Silesian University of of TechnologyGliwice, Poland.
    Wigenius, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology. Carl Zeiss AB, Sweden.
    Karlsson, Thommie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Application Specialist Confocal Microscopy at Leica MicrosystemsIL, United States.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Department of Pathology, Pomeranian Medical UniversitySzczecin, Poland.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte2015In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed)
    Abstract [en]

    Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

  • 221.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Los, Marek J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Peter R.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells2015In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed)
    Abstract [en]

    Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

  • 222.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Simon, Rozalyn
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Joshi-Barr, Shivanjali
    University of Calif San Diego.
    Sigurdson, Christina
    University of Calif San Diego.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Conformation-sensitive probes for strain-specific characterization of prion aggregates in PRION, vol 6, issue , pp 47-472012In: PRION, Landes Bioscience , 2012, Vol. 6, p. 47-47Conference paper (Refereed)
    Abstract [en]

    n/a

  • 223.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Simon, Rozalyn
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Sjölander, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Sigurdson, Christina J.
    Department of Pathology, Unversity of California, San Diego, USA.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Nilsson, Peter R
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands2014In: Prion, ISSN 1933-6896, E-ISSN 1933-690X, Vol. 8, no 4, p. 319-329Article in journal (Refereed)
    Abstract [en]

    The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

  • 224.
    Mahajan, Vineet
    et al.
    Medical University of Graz.
    Klingstedt, Therése
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Simon, Rozalyn
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Thueringer, Andrea
    Medical University of Graz.
    Kashofer, Karl
    Medical University of Graz.
    Haybaeck, Johannes
    Medical University of Graz.
    Denk, Helmut
    Medical University of Graz.
    Abuja, Peter M
    Medical University of Graz.
    Zatloukal, Kurt
    Medical University of Graz.
    Cross beta-Sheet Conformation of Keratin 8 Is a Specific Feature of Mallory-Denk Bodies Compared With Other Hepatocyte Inclusions2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, p. 1080-U428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND andamp; AIMS: Mallory-Denk bodies (MDBs) are cytoplasmic protein aggregates in hepatocytes in steato-hepatitis and other liver diseases. We investigated the molecular structure of keratin 8 (K8) and 18 (K18), sequestosome 1/p62, and ubiquitin, which are the major constituents of MDBs, to investigate their formation and role in disease pathogenesis. METHODS: Luminescent conjugated oligothiophenes (LCOs), h-HTAA, and p-FTAA are fluorescent amyloid ligands that specifically bind proteins with cross beta-sheet conformation. We used LCOs to investigate conformational changes in MDBs in situ in human and murine livers as well as in transfection studies. RESULTS: LCO analysis showed cross beta-sheet conformation in human MDBs from patients with alcoholic and nonalcoholic steatohepatitis or hepatocellular carcinoma, but not in intracellular hyaline bodies, alpha(1)-antitrypsin deficiency, or ground-glass inclusions. LCOs bound to MDBs induced by 3,5diethoxycarbonyl-1,4-dihydrocollidine feeding of mice at all developmental stages. CHO-K1 cells transfected with various combinations of SQSTM1/p62, ubi, and Krt8/Krt18 showed that K8 was more likely to have cross beta-sheet conformation than K18, whereas p62 never had cross beta-sheet conformation. The different conformational properties of K8 and K18 were also shown by circular dichroism analysis. CONCLUSIONS: K8 can undergo conformational changes from predominantly alpha-helical to cross beta-sheet, which would allow it to form MDBs. These findings might account for the observation that krt8(-/-) mice do not form MDBs, whereas its excess facilitates MDB formation. LCOs might be used in diagnosis of liver disorders; they can be applied to formalin-fixed, paraffin-embedded tissues to characterize protein aggregates in liver cells.

  • 225.
    Mahler, Jasmin
    et al.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Morales-Corraliza, Jose
    Nathan S Kline Institute Psychiat Research, NY 10962 USA; NYU, NY USA.
    Stolz, Julia
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Skodras, Angelos
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Radde, Rebecca
    University of Tubingen, Germany.
    Duma, Carmen C.
    University of Tubingen, Germany.
    Eisele, Yvonne S.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Mazzella, Matthew J.
    Nathan S Kline Institute Psychiat Research, NY 10962 USA.
    Wong, Harrison
    Nathan S Kline Institute Psychiat Research, NY 10962 USA.
    Klunk, William E.
    NYU, NY USA; University of Pittsburgh, PA USA; University of Pittsburgh, PA 15261 USA.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Staufenbiel, Matthias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Mathews, Paul M.
    Nathan S Kline Institute Psychiat Research, NY 10962 USA; NYU, NY USA.
    Jucker, Mathias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Wegenast-Braun, Bettina M.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Endogenous murine A beta increases amyloid deposition in APP23 but not in APPPS1 transgenic mice2015In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 36, no 7, p. 2241-2247Article in journal (Refereed)
    Abstract [en]

    Endogenous murine amyloid-beta peptide (A beta) is expressed in most A beta precursor protein (APP) transgenic mouse models of Alzheimers disease but its contribution to beta-amyloidosis remains unclear. We demonstrate similar to 35% increased cerebral A beta load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster A beta-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine A beta, and immunoelectron microscopy revealed a tight association of murine A beta with human A beta fibrils. Deposition of murine A beta was considerably less efficient compared with the deposition of human A beta indicating a lower amyloidogenic potential of murine A beta in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human A beta and deposits of mixed human-murine A beta. Our data demonstrate a differential effect of murine A beta on human A beta deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse A beta may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.

  • 226.
    Maiwulidan, Yimamu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering. European Spallat Source ERIC, Sweden.
    Höglund, Carina
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. European Spallat Source ERIC, Sweden.
    Jensen, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Schmidt, Susann
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering. European Spallat Source ERIC, Sweden.
    Ivanov, Ivan Gueorguiev
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Hall-Wilton, Richard
    European Spallat Source ERIC, Sweden; Mid Sweden University, Sweden.
    Birch, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Trimethylboron as Single-Source Precursor for Boron-Carbon Thin Film Synthesis by Plasma Chemical Vapor Deposition2016In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 120, no 38, p. 21990-21997Article in journal (Refereed)
    Abstract [en]

    Boron–carbon (BxC) thin films are potential neutron converting layers for 10B-based neutron detectors. However, as common material choices for such detectors do not tolerate temperatures above 500 °C, a low temperature deposition route is required. Here, we study trimethylboron B(CH3)3 (TMB) as a single-source precursor for the deposition of BxC thin films by plasma CVD using Ar plasma. The effect of plasma power, TMB/Ar flow ratio and total pressure, on the film composition, morphology, chemical bonding, and microstructures are investigated. Dense and boron-rich films (B/C = 1.9) are achieved at high TMB flow under a low total pressure and high plasma power, which rendered an approximate substrate temperature of ∼300 °C. Films mainly contain B–C bonds with the presence of B–O and C–C, which is attributed to be the origin of formed amorphous carbon in the films. The high H content (15 ± 5 at. %) is almost independent of deposition parameters and contributed to lower the film density (2.16 g/cm3). The plasma compositional analysis shows that the TMB molecule decomposes to mainly atomic H, C2, BH, and CH. A plasma chemical model for the decomposition of TMB with BH and CH as the plausible film depositing species in the plasma is proposed.

  • 227.
    Maji, Samir K
    et al.
    ETH.
    Perrin, Marilyn H
    Salk Institute of Biological Studies.
    Sawaya, Michael R
    University of California.
    Jessberger, Sebastian
    ETH.
    Vadodaria, Krishna
    ETH.
    Rissman, Robert A
    University of California .
    Singru, Praful S
    Tufts Medical Centre.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Simon, Rozalyn
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Schubert, David
    Salk Institute of Biological Studies.
    Eisenberg, David
    University of California.
    Rivier, Jean
    Salk Institute of Biological Studies.
    Sawchenko, Paul
    Salk Institute of Biological Studies.
    Vale, Wylie
    Salk Institute of Biological Studies.
    Riek, Roland
    ETH.
    Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules2009In: SCIENCE, ISSN 0036-8075, Vol. 325, no 5938, p. 328-332Article in journal (Refereed)
    Abstract [en]

    Amyloids are highly organized cross-beta-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimers disease and type II diabetes. However, amyloids may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.

  • 228.
    Malysheva, Lyuba
    et al.
    Bogolyubov Institute for Theoretical Physics, 03680, Kiev, Ukraine.
    Onipko, Alexander
    Bogolyubov Institute for Theoretical Physics, 03680, Kiev, Ukraine.
    Fyrner, Timmy
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lee, Hung-Hsun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Valiokas, Ramūnas
    Department of Nanoengineering, Center for Physical Sciences and Engineering, Savanoriu 231, LT-02300 Vilnius, Lithuania.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Spectroscopic Characterization and Modeling of Methyl- and Hydrogen-Terminated Oligo (ethylene glycol) Self-Assembled Monolayers2012In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 116, no 22, p. 12008-12016Article in journal (Refereed)
    Abstract [en]

    Two series of oligo (ethylene glycol) (OEG) thiol compounds HS-(CH2CH2O)nR with R = CH3, H and n = 5, 6, 7, have been synthesized and used to form self-assembled monolayers (SAMs) on gold. The data from null ellipsometry, infrared reflection-absorption spectroscopy and ab initio calculations of this type of OH- and CH3-terminated OEG SAMs are used to examine the rarely addressed in-SAM orientation of oligo (ethylene glycols) and to provide detailed assignments of infrared bands in the fingerprint and CH-stretching regions. Based on these results, a new spectral band has been observed at 2947 cm-1 and identified by the firstprinciple calculations as localized vibrations that are specific for hydrogen-terminated OEG thiolate SAMs. This band can be used as an indicator of a high crystalline like ordering. It is further more stressed that theory agrees with the experimentally obtained CH-stretching spectra remarkably well if, and only if, the OEG helix axis within studied SAMs is tilted by about 20o with respect to the surface normal.

  • 229.
    Margalith, Ilan
    et al.
    University of Zurich Hospital, Switzerland .
    Suter, Carlo
    University of Zurich Hospital, Switzerland .
    Ballmer, Boris
    University of Zurich Hospital, Switzerland .
    Schwarz, Petra
    University of Zurich Hospital, Switzerland .
    Tiberi, Cinzia
    University of Zurich Hospital, Switzerland .
    Sonati, Tiziana
    University of Zurich Hospital, Switzerland .
    Falsig, Jeppe
    University of Zurich Hospital, Switzerland .
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Åslund, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Yam, Alice
    Novartis Diagnost, USA .
    Whitters, Eric
    Novartis Diagnost, USA .
    Hornemann, Simone
    University of Zurich Hospital, Switzerland .
    Aguzzi, Adriano
    University of Zurich Hospital, Switzerland .
    Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates2012In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 23, p. 18872-18887Article in journal (Refereed)
    Abstract [en]

    Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.

  • 230.
    Mayzel, Maxim
    et al.
    University of Gothenburg, Sweden.
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Orekhov, Vladislav Y.
    University of Gothenburg, Sweden.
    Measurement of protein backbone (CO)-C-13 and N-15 relaxation dispersion at high resolution2017In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 69, no 1Article in journal (Refereed)
    Abstract [en]

    Peak overlap in crowded regions of two-dimensional spectra prevents characterization of dynamics for many sites of interest in globular and intrinsically disordered proteins. We present new three-dimensional pulse sequences for measurement of Carr-Purcell-Meiboom-Gill relaxation dispersions at backbone nitrogen and carbonyl positions. To alleviate increase in the measurement time associated with the additional spectral dimension, we use non-uniform sampling in combination with two distinct methods of spectrum reconstruction: compressed sensing and co-processing with multi-dimensional decomposition. The new methodology was validated using disordered protein CD79A from B-cell receptor and an SH3 domain from Abp1p in exchange between its free form and bound to a peptide from the protein Ark1p. We show that, while providing much better resolution, the 3D NUS experiments give the similar accuracy and precision of the dynamic parameters to ones obtained using traditional 2D experiments. Furthermore, we show that jackknife resampling of the spectra yields robust estimates of peak intensities errors, eliminating the need for recording duplicate data points.

  • 231. McDonald, S
    et al.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Singer, Sherwin J.
    Graph theoretical generation and analysis of hydrogen-bonded structures with applications to the neutral and protonated water cube and dodecahedral clusters1998In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 102, no 17, p. 2824-2832Article in journal (Refereed)
    Abstract [en]

    Graph theoretical techniques are demonstrated to be of considerable use in the search for stable arrangements of water clusters. inspired by the so-called "ice rules" that govern which hydrogen-bond networks are physically possible in the condensed phase, we use graphical techniques to generate a multitude of local minima of neutral and protonated water clusters using oriented graph theory. Efficient techniques to precisely enumerate all possible hydrogen-bonding topologies are presented. Empirical rules regarding favorable water neighbor geometries are developed that indicate which of the multitude of hydrogen-bonding topologies available to large water clathrates (e.g., 30 026 for (H2O)(20)) are likely to be the most stable structures. The cubic (H2O)(8) and dodecahedral (H2O)(20) clusters and their protonated analogues are treated as examples. In these structures every molecule is hydrogen bonded to three others, which lends to hydrogen-bonding topology fixing the cluster geometry. Graphical techniques can also be applied to geometrically irregular structures as well. The enumerated oriented graphs are used to generate initial guesses for optimization using various potential models. The hydrogen-bonding topology was found to have a significant effect on cluster stability, even though the total number of hydrogen bonds is conserved. For neutral clusters, the relationship between oriented graphs and local minima of several potential models appears to be one-to-one. The stability of the different topologies is rationalized primarily in terms of the number of nearest neighbor pairs that both have a free OH bond. This lends to the identification of water dodecahedra of greatest stability.

  • 232.
    Michno, Wojciech
    et al.
    Univ Gothenburg, Sweden.
    Kaya, Ibrahim
    Univ Gothenburg, Sweden.
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Guerard, Laurent
    Univ Gothenburg, Sweden; Univ Basel, Switzerland.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL, England.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England; Chalmers Univ Technol, Sweden.
    Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 13, p. 8130-8138Article in journal (Refereed)
    Abstract [en]

    Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimers disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, A beta deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric A beta into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A beta plaques, including cored/compact- and diffuse, may be linked to their distinct A beta profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPP(Swe)) and was correlated to A beta profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse A beta structures and correlate with A beta 1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A beta deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.

  • 233.
    Michno, Wojciech
    et al.
    Univ Gothenburg, Sweden.
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wehrli, Patrick
    Univ Gothenburg, Sweden.
    Lashley, Tammaryn
    UCL, England.
    Brinkmalm, Gunnar
    Univ Gothenburg, Sweden.
    Guerard, Laurent
    Univ Gothenburg, Sweden.
    Syvanen, Stina
    Uppsala Univ, Sweden.
    Sehlin, Dag
    Uppsala Univ, Sweden.
    Kaya, Ibrahim
    Univ Gothenburg, Sweden.
    Brinet, Dimitri
    Univ Gothenburg, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; UCL, England; Sahlgrens Univ Hosp, Sweden; UCL, England.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England.
    Pyroglutamation of amyloid-x-42 (Ax-42) followed by A1-40 deposition underlies plaque polymorphism in progressing Alzheimers disease pathology2019In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 294, no 17, p. 6719-6732Article in journal (Refereed)
    Abstract [en]

    Amyloid-β (Aβ) pathology in Alzheimer's disease (AD) is characterized by the formation of polymorphic deposits comprising diffuse and cored plaques. Because diffuse plaques are predominantly observed in cognitively unaffected, amyloid-positive (CU-AP) individuals, pathogenic conversion into cored plaques appears to be critical to AD pathogenesis. Herein, we identified the distinct Aβ species associated with amyloid polymorphism in brain tissue from individuals with sporadic AD (s-AD) and CU-AP. To this end, we interrogated Aβ polymorphism with amyloid conformation–sensitive dyes and a novel in situ MS paradigm for chemical characterization of hyperspectrally delineated plaque morphotypes. We found that maturation of diffuse into cored plaques correlated with increased Aβ1–40 deposition. Using spatial in situ delineation with imaging MS (IMS), we show that Aβ1–40 aggregates at the core structure of mature plaques, whereas Aβ1–42 localizes to diffuse amyloid aggregates. Moreover, we observed that diffuse plaques have increased pyroglutamated Aβx-42 levels in s-AD but not CU-AP, suggesting an AD pathology–related, hydrophobic functionalization of diffuse plaques facilitating Aβ1–40 deposition. Experiments in tgAPPSwe mice verified that, similar to what has been observed in human brain pathology, diffuse deposits display higher levels of Aβ1–42 and that Aβ plaque maturation over time is associated with increases in Aβ1–40. Finally, we found that Aβ1–40 deposition is characteristic for cerebral amyloid angiopathy deposition and maturation in both humans and mice. These results indicate that N-terminal Aβx-42 pyroglutamation and Aβ1–40 deposition are critical events in priming and maturation of pathogenic Aβ from diffuse into cored plaques, underlying neurotoxic plaque development in AD.

  • 234.
    Mishra, Rajesh
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Jawaharlal Nehru Univ, India.
    Elgland, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Begum, Afshan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Fyrner, Timmy
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Impact of N-glycosylation site variants during human PrP aggregation and fibril nucleation2019In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1867, no 10, p. 909-921Article in journal (Refereed)
    Abstract [en]

    Misfolding and aggregation of the human prion protein (PrP) cause neurodegenerative transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease. Mature native PrP is composed of 209 residues and is folded into a C-terminal globular domain (residues 125-209) comprising a small two-stranded beta-sheet and three alpha-helices. The N-terminal domain (residues 23-124) is intrinsically disordered. Expression of truncated PrP (residues 90-231) is sufficient to cause prion disease and residues 90/100-231 is comprising the amyloid-like fibril core of misfolded infectious PrP. During PrP fibril formation under native conditions in vitro, the disordered N-terminal domain slows down fibril formation likely due to a mechanism of initial aggregation forming morphologically disordered aggregates. The morphological disordered aggregate is a transient phase. Nucleation of fibrils occurs from this initial aggregate. The aggregate phase is largely circumvented by seeding with preformed PrP fibrils. In vivo PrP is N-glycosylated at positions Asn181 and Asn197. Little is known about the importance of these positions and their glycans for PrP stability, aggregation and fibril formation. We have in this study taken a step towards that goal by mutating residues 181 and 197 for cysteines to study the positional impact on these processes. We have further by organic synthetic chemistry and chemical modification generated synthetic glycosylations in these positions. Our data shows that residue 181 when mutated to a cysteine is a key residue for self -chaperoning, rendering a trap in the initial aggregate preventing conformational changes towards amyloid fibril formation. Position 197 is less involved in the aggregate trapping and is more geared towards beta-sheet structure conversion within amyloid fibrils. As expected, synthetic glycosylated 197 is less affected towards fibril formation compared to glycosylated 181. Our data are rather compatible with the parallel in-register intermolecular beta-sheet model structure of the PrP90-231 fibril and sheds light on the misfolding transitions of PrP in vitro. We hypothesize that glycosylation of position 181 is a key site for prion strain differentiation in vivo.

  • 235.
    Moparthi, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Fristedt, Rikard
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Mishra, Rajesh
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Almstedt, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Karlsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Chaperone activity of Cyp18 through hydrophobic condensation that enables rescue of transient misfolded molten globule intermediates2010In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 49, no 6, p. 1137-1145Article in journal (Refereed)
    Abstract [en]

    The single-domain cyclophilin 18 (Cyp18) has long been known to function as a peptidyl-prolyl cis/trans isomerase (PPI) and was proposed by us to also function as a chaperone [Freskgård, P.-O., Bergenhem, N., Jonsson, B.-H., Svensson, M., and Carlsson, U. (1992) Science 258, 466−468]. Later several multidomain PPIs were demonstrated to work as both a peptidyl-prolyl cis/trans isomerase and a chaperone. However, the chaperone ability of Cyp18 has been debated. In this work, we add additional results that show that Cyp18 can both accelerate the rate of refolding and increase the yield of native protein during the folding reaction, i.e., function as both a folding catalyst and a chaperone. Refolding experiments were performed using severely destabilized mutants of human carbonic anhydrase II under conditions where the unfolding reaction is significant and a larger fraction of a more destabilized variant populates molten globule-like intermediates during refolding. A correlation of native state protein stability of the substrate protein versus Cyp18 chaperone activity was demonstrated. The induced correction of misfolded conformations by Cyp18 likely functions through rescue from misfolding of transient molten globule intermediates. ANS binding data suggest that the interaction by Cyp18 leads to an early stage condensation of accessible hydrophobic portions of the misfolding-prone protein substrate during folding. The opposite effect was observed for GroEL known as an unfoldase at early stages of refolding. The chaperone effect of Cyp18 was also demonstrated for citrate synthase, suggesting a general chaperone effect of this PPI.

  • 236.
    Moparthi, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    A nonessential role for Arg 55 in cyclophilin18 for catalysis of proline isomerization during protein folding2009In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 18, no 2, p. 475-479Article in journal (Refereed)
    Abstract [en]

    The protein folding process is often in vitro rate-limited by slow cis-trans proline isomerization steps. Importantly, the rate of this process in vivo is accelerated by prolyl isomerases (PPIases). The archetypal PPIase is the human cyclophilin 18 (Cyp18 or CypA), and Arg 55 has been demonstrated to play a crucial role when studying short peptide substrates in the catalytic action of Cyp18 by stabilizing the transition state of isomerization. However, in this study we show that a R55A mutant of Cyp18 is as efficient as the wild type to accelerate the refolding reaction of human carbonic anhydrase II (HCA II). Thus, it is evident that the active-site located Arg 55 is not required for catalysis of the rate-limiting prolyl cis-trans isomerization steps during the folding of a protein substrate as HCA II. Nevertheless, catalysis of cis-trans proline isomerization in HCA II occurs in the active-site of Cyp18, since binding of the inhibitor cyclosporin A abolishes rate acceleration of the refolding reaction. Obviously, the catalytic mechanisms of Cyp18 can differ when acting upon a simple model peptide, four residues long, with easily accessible Pro residues compared with a large protein molecule undergoing folding with partly or completely buried Pro residues. In the latter case, the isomerization kinetics are significantly slower and simpler mechanistic factors such as desolvation and/or strain might operate during folding-assisted catalysis, since binding to the hydrophobic active site is still a prerequisite for catalysis.

  • 237.
    Moparthi, Vamsi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Uppsala Univ, Sweden.
    Moparthi, Satish B.
    Aix Marseille Univ, France; Inst Pasteur, France.
    Howe, Christoph
    Uppsala Univ, Sweden.
    Raleiras, Patricia
    Uppsala Univ, Sweden; Medicago AB, Sweden.
    Wenger, Jerome
    Aix Marseille Univ, France.
    Stensjo, Karin
    Uppsala Univ, Sweden.
    Structural diffusion properties of two atypical Dps from the cyanobacterium Nostoc punctiforme disclose interactions with ferredoxins and DNA2019In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1860, no 9, article id 148063Article in journal (Refereed)
    Abstract [en]

    Ferritin-like proteins, Dps (DNA-binding protein from starved cells), store iron and play a key role in the iron homeostasis in bacteria, yet their iron releasing machinery remains largely unexplored. The electron donor proteins that may interact with Dps and promote the mobilization of the stored iron have hitherto not been identified. Here, we investigate the binding capacity of the two atypical Dps proteins NpDps4 and NpDps5 from Nostoc punctiforme to isolated ferredoxins. We report NpDps-ferredoxin interactions by fluorescence correlation spectroscopy (FCS) and fluorescence resonance energy transfer (FRET) methods. Dynamic light scattering, size exclusion chromatography and native gel electrophoresis results show that NpDps4 forms a dodecamer at both pH 6M and pH 8.0, while NpDps5 forms a dodecamer only at pH 6.0. In addition, FCS data clearly reveal that the non-canonical NpDps5 interacts with DNA at pH 6.0. Our spectroscopic analysis shows that [Fe-S] centers of the three recombinantly expressed and isolated ferredoxins are properly incorporated and are consistent with their respective native states. The results support our hypothesis that ferredoxins could be involved in cellular iron homeostasis by interacting with Dps and assisting the release of stored iron.

  • 238.
    Moren, Lina
    et al.
    FOI, Sweden.
    Qvarnstrom, Johanna
    FOI, Sweden.
    Engqvist, Magnus
    FOI, Sweden.
    Afshin-Sander, Robin
    FOI, Sweden.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Dahlén, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Löfberg, Christian
    Swedish Natl Forens Ctr, Linkoping, Sweden.
    Larsson, Andreas
    FOI, Sweden.
    Ostin, Anders
    FOI, Sweden.
    Attribution of fentanyl analogue synthesis routes by multivariate data analysis of orthogonal mass spectral data2019In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 203, p. 122-130Article in journal (Refereed)
    Abstract [en]

    Chemical attribution signatures (CAS) can be used to obtain useful forensic information and evidence from illicit drug seizures. A CAS is typically generated using hyphenated chemical analysis techniques and consists of a fingerprint of the by-products and additives present in a sample. Among other things, it can provide information on the samples origin, its method of production, and the sources of its precursors. This work investigates the possibility of using multivariate CAS analysis to identify the synthetic methods used to prepare seized fentanyl analogues, independently of the analogues acyl derivatization. Three chemists working in two labs synthesized three different fentanyl analogues, preparing each one in duplicate by six different routes. The final collection of analogues (96 samples) and two intermediates (16 + 32 samples) were analysed by GC-MS and UHPLC-HRMS, and the resulting analytical data were used for multivariate modelling. Independently of analogue structure, the tested fentanyls could be classified based on the method used in the first step of their synthesis. The multivariate models ability to classify unknown samples was then evaluated by applying it to six new fentanyl analogues. Additionally, seized fentanyl samples was analysed and classified by the model.

  • 239.
    Mårtensson, Lars-Göran
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Karlsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Dramatic stabilization of the native state of human carbonic anhydrase II by an engineered disulfide bond2002In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 41, no 52, p. 15867-15875Article in journal (Refereed)
    Abstract [en]

    To find a disulfide pair that could stabilize the enzyme human carbonic anhydrase II (HCA II), we grafted the disulfide bridge from the related and unusually stable carbonic anhydrase form from Neisseria gonorrhoeae (NGCA) into the human enzyme. Thus, the two Cys residues at positions 23 and 203 were engineered into a pseudo-wild-type form of HCA II (C206S), giving the mutant C206S/A23C/L203C. The disulfide bond was not formed spontaneously. The native state of the reduced form of the mutant was markedly destabilized (2.9 kcal/mol) compared to that of HCA II. Formation of a disulfide bridge was achieved by treatment by oxidized glutathione. This led to a significant stabilization of the native conformation. Compared to HCA II the unfolding midpoint for the variant was increased from 0.9 to 1.7 M guanidine HCl, corresponding to a stabilization of 3.7 kcal/mol. This makes the human enzyme almost as stable as the model protein NGCA, for which the unfolding of the native state has a midpoint at 2.1 M guanidine HCl. The stabilized protein underwent, contrary to all other investigated variants of HCA II, an apparent two-state unfolding transition, as judged from intrinsic Trp fluorescence measurements. A molten−globule intermediate is nevertheless formed but is suppressed because of the high denaturant pressure it faces upon rupture of the native state.

  • 240.
    Müller, Christian
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Jansson, Ronnie
    Department of Anatomy, Physiology and Biochemistry, SLU, Biomedical Centre, Uppsala, Sweden.
    Elfwing, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Askarieh, Glareh
    Department of Molecular Biology, Uppsala BioCenter, SLU, Biomedical Centre, Uppsala, Sweden .
    Karlsson, Roger
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Hamedi, Mahiar
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Rising, Anna
    Department of Anatomy, Physiology and Biochemistry, SLU, Biomedical Centre, Uppsala, Sweden .
    Johansson, Jan
    Department of Anatomy, Physiology and Biochemistry, SLU, Biomedical Centre, Uppsala, Sweden .
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Hedhammar, My
    Department of Anatomy, Physiology and Biochemistry, SLU, Biomedical Centre, Uppsala, Sweden .
    Functionalisation of recombinant spider silk with conjugated polyelectrolytes2011In: Journal of Materials Chemistry, ISSN 0959-9428, E-ISSN 1364-5501, Vol. 21, no 9, p. 2909-2915Article in journal (Refereed)
    Abstract [en]

    Conjugated polyelectrolytes are demonstrated to permit facile staining of recombinant spider silk fibres. We find that the polyelectrolyte concentration and pH of the staining solution as well as the incubation temperature strongly influence the efficiency of this self-assembly process, which appears to be principally mediated through favourable electrostatic interactions. Thus, depending on the choice of staining conditions as well as the polyelectrolyte, electrically conductive or photoluminescent recombinant silk fibres could be produced. In addition, staining of natural Bombyx mori silk is established, which emphasises the versatility of the here advanced approach to functionalise silk-based materials.

  • 241.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junjang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Abdiu, Avni
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Nayeri, Tayeb
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Health Sciences.
    Autocrine production of biologically active hepatocyte growth factor (HGF) by injured human skin2006In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 43, no 1, p. 49-56Article in journal (Refereed)
    Abstract [en]

    Background

    Hepatocyte growth factor (HGF) is a potent regenerative factor involved in wound healing. Previous studies have shown that mesenchymal cells produce HGF, stimulating epithelial cells in a paracrine fashion.

    Objective

    To examine whether autocrine HGF production by keratinocytes can occur upon skin injury.

    Methods

    A 31-year-old male patient sustained a burn affecting 80% of his total body surface area. Biopsies were taken from intact skin near the injured area, and skin keratinocytes were separated and cultured. Conditioned medium from keratinocytes was analyzed for HGF by ELISA, surface plasmon resonance (SPR), and dot blotting. Binding of HGF from conditioned medium to its receptor, c-Met, was compared with recombinant HGF by SPR. Finally, we examined the motogenic effect on mouse transformed skin epithelial cells (CCL-53.1) of HGF from conditioned medium.

    Results

    HGF was detected in the cultured keratinocyte medium. Similar to recombinant HGF, HGF from conditioned medium had a high affinity for dextran sulfate and albumin, and the same epitopes were engaged by the interaction of HGF with the c-Met receptor. The conditioned medium from keratinocytes obtained from the burn patient, but not medium from keratinocytes obtained from healthy volunteers, accelerated the motogenesis of CCL-53.1 cells. Unexpectedly, anti-HGF antibodies did not prevent this effect. However, anti-c-Met antibodies completely inhibited the motogenic effect.

    Conclusion

    Upon injury, human skin keratinocytes might produce biologically active HGF in an autocrine fashion. This HGF might have different structural and/or biological properties from HGF produced by mesenchymal cells.

  • 242.
    Nemez, Emma
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Substitution of amaranth as dye in edge wicking test2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Stora Enso, a big Swedish-Finnish forest industry company, wants to find a substitute for the dye that is used in their edge wick analyzes. The dye amaranth, that is used today, is a classified substance that is unhealthy and hazardous. It causes irritation to the eyes, skin and respiratory system. Edge wick is a method to determine the amount of penetrated liquid into the unprotected edges of a packaging board (the surfaces are covered with plastic). It is important to analyze liquid penetration to know that the board will sustain the liquids that it might be exposed to, for example sterilizing liquid (hydrogen peroxide), juice or wine. The dye is used as coloring agent for colorless solutions to enable visual evaluation of the penetration. In the present study several colorants were screened and evaluated in edge wick tests with the standard test liquids used at Stora Enso. Machine, pilot and handmade boards were used in the tests. Surface tension of some test liquids was also determined, as it is important to know if the dyes change the liquid properties since this may influence the penetration. The result of the tests was that a new dye was found, Allura red AC. It has a similar chemical structure to amaranth and seems to act in the same way in different type of test conditions. The recommendation is that amaranth be substituted for allura red AC, since the latter is less hazardous and is not a classified substance.

  • 243.
    Newton, Matilda S.
    et al.
    University of Otago, New Zealand.
    Guo, Xiaohu
    Uppsala University, Sweden.
    Söderholm, Annika
    Uppsala University, Sweden.
    Näsvall, Joakim
    Uppsala University, Sweden.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Andersson, Dan I.
    Uppsala University, Sweden.
    Selmer, Maria
    Uppsala University, Sweden.
    Patrick, Wayne M.
    University of Otago, New Zealand.
    Structural and functional innovations in the real-time evolution of new (beta alpha)(8) barrel enzymes2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 18, p. 4727-4732Article in journal (Refereed)
    Abstract [en]

    New genes can arise by duplication and divergence, but there is a fundamental gap in our understanding of the relationship between these genes, the evolving proteins they encode, and the fitness of the organism. Here we used crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the molecular innovations that arose during a previous real-time evolution experiment. In that experiment, the (beta alpha)(8) barrel enzyme HisA was under selection for two functions (HisA and TrpF), resulting in duplication and divergence of the hisA gene to encode TrpF specialists, HisA specialists, and bifunctional generalists. We found that selection affects enzyme structure and dynamics, and thus substrate preference, simultaneously and sequentially. Bifunctionality is associated with two distinct sets of loop conformations, each essential for one function. We observed two mechanisms for functional specialization: structural stabilization of each loop conformation and substrate-specific adaptation of the active site. Intracellular enzyme performance, calculated as the product of catalytic efficiency and relative expression level, was not linearly related to fitness. Instead, we observed thresholds for each activity above which further improvements in catalytic efficiency had little if any effect on growth rate. Overall, we have shown how beneficial substitutions selected during real-time evolution can lead to manifold changes in enzyme function and bacterial fitness. This work emphasizes the speed at which adaptive evolution can yield enzymes with sufficiently high activities such that they no longer limit the growth of their host organism, and confirms the (beta alpha)(8) barrel as an inherently evolvable protein scaffold.

  • 244.
    Niklasson, Markus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Coding to cure: NMR and thermodynamic software applied to congenital heart disease research2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Regardless of scientific field computers have become pivotal tools for data analysis and the field of structural biology is not an exception. Here, computers are the main tools used for tasks including structural calculations of proteins, spectral analysis of nuclear magnetic resonance (NMR) spectroscopy data and fitting mathematical models to data. As results reported in papers heavily rely on software and scripts it is of key importance that the employed computational methods are robust and yield reliable results. However, as many scientific fields are niched and possess a small potential user base the task to develop necessary software often falls on researchers themselves. This can cause divergence when comparing data analyzed by different measures or by using subpar methods. Therein lies the importance of development of accurate computational methods that can be employed by the scientific community.

    The main theme of this thesis is software development applied to structural biology, with the purpose to aid research in this scientific field by speeding up the process of data analysis as well as to ensure that acquired data is properly analyzed. Among the original results of this thesis are three user-friendly software:

    COMPASS - a resonance assignment software for NMR spectroscopy data capable of analyzing chemical shifts and providing the user with suggestions to potential resonance assignments, based on a meticulous database comparison.

    CDpal - a curve fitting software used to fit thermal and chemical denaturation data of proteins acquired by circular dichroism (CD) spectroscopy or fluorescence spectroscopy.

    PINT - a line shape fitting and downstream analysis software forNMRspectroscopy data, designed with the important purpose to easily and accurately fit peaks in NMR spectra and extract parameters such as relaxation rates, intensities and volumes of peaks.

    This thesis also describes a study performed on variants of the life essential regulatory protein calmodulin that have been associated with the congenital life threatening heart disease long QT syndrome (LQTS). The study provided novel insights revealing that all variants are distinct from the wild type in regards to structure and dynamics on a detailed level; the presented results are useful for the interpretation of results from protein interaction studies. The underlying research of this paper makes use of all three developed software, which validates that all developed methods fulfil a scientific purpose and are capable of producing solid results.

    List of papers
    1. Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches
    Open this publication in new window or tab >>Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches
    Show others...
    2015 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 1, p. e1004022-Article in journal (Refereed) Published
    Abstract [en]

    The process of resonance assignment is fundamental to most NMR studies of protein structure and dynamics. Unfortunately, the manual assignment of residues is tedious and time-consuming, and can represent a significant bottleneck for further characterization. Furthermore, while automated approaches have been developed, they are often limited in their accuracy, particularly for larger proteins. Here, we address this by introducing the software COMPASS, which, by combining automated resonance assignment with manual intervention, is able to achieve accuracy approaching that from manual assignments at greatly accelerated speeds. Moreover, by including the option to compensate for isotope shift effects in deuterated proteins, COMPASS is far more accurate for larger proteins than existing automated methods. COMPASS is an open-source project licensed under GNU General Public License and is available for download from http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en. Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.

    Place, publisher, year, edition, pages
    Public Library of Science, 2015
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-115010 (URN)10.1371/journal.pcbi.1004022 (DOI)000349309400013 ()25569628 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [Dnr. 2012-5136]

    Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-12-04
    2. Robust and convenient analysis of protein thermal and chemical stability
    Open this publication in new window or tab >>Robust and convenient analysis of protein thermal and chemical stability
    Show others...
    2015 (English)In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 24, no 12, p. 2055-2062Article in journal (Refereed) Published
    Abstract [en]

    We present the software CDpal that is used to analyze thermal and chemical denaturation data to obtain information on protein stability. The software uses standard assumptions and equations applied to two-state and various types of three-state denaturation models in order to determine thermodynamic parameters. It can analyze denaturation monitored by both circular dichroism and fluorescence spectroscopy and is extremely flexible in terms of input format. Furthermore, it is intuitive and easy to use because of the graphical user interface and extensive documentation. As illustrated by the examples herein, CDpal should be a valuable tool for analysis of protein stability.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2015
    Keywords
    protein stability; thermal denaturation; chemical denaturation; circular dichroism; fluorescence; curve fitting; protein stability software; protein denaturation software
    National Category
    Chemical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-124648 (URN)10.1002/pro.2809 (DOI)000368292000014 ()26402034 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [2012-5136]; LiU Cancer

    Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2017-11-30
    3. Comprehensive analysis of NMR data using advanced line shape fitting.
    Open this publication in new window or tab >>Comprehensive analysis of NMR data using advanced line shape fitting.
    Show others...
    2017 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 69, no 2, p. 93-99Article in journal (Refereed) Published
    Abstract [en]

    NMR spectroscopy is uniquely suited for atomic resolution studies of biomolecules such as proteins, nucleic acids and metabolites, since detailed information on structure and dynamics are encoded in positions and line shapes of peaks in NMR spectra. Unfortunately, accurate determination of these parameters is often complicated and time consuming, in part due to the need for different software at the various analysis steps and for validating the results. Here, we present an integrated, cross-platform and open-source software that is significantly more versatile than the typical line shape fitting application. The software is a completely redesigned version of PINT ( https://pint-nmr.github.io/PINT/ ). It features a graphical user interface and includes functionality for peak picking, editing of peak lists and line shape fitting. In addition, the obtained peak intensities can be used directly to extract, for instance, relaxation rates, heteronuclear NOE values and exchange parameters. In contrast to most available software the entire process from spectral visualization to preparation of publication-ready figures is done solely using PINT and often within minutes, thereby, increasing productivity for users of all experience levels. Unique to the software are also the outstanding tools for evaluating the quality of the fitting results and extensive, but easy-to-use, customization of the fitting protocol and graphical output. In this communication, we describe the features of the new version of PINT and benchmark its performance.

    Place, publisher, year, edition, pages
    Springer, 2017
    Keywords
    Dynamics, Line shape fitting, Peak integration, Relaxation, Spectral analysis
    National Category
    Biochemistry and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-142786 (URN)10.1007/s10858-017-0141-6 (DOI)000414206400004 ()29043470 (PubMedID)2-s2.0-85031497711 (Scopus ID)
    Note

    Funding agencies: Swedish Research Council [2012-5136]

    Available from: 2017-11-03 Created: 2017-11-03 Last updated: 2017-12-04Bibliographically approved
  • 245.
    Niklasson, Markus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Andrésen, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Marsh, Joseph A.
    University of Edinburgh, Scotland.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches2015In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 1, p. e1004022-Article in journal (Refereed)
    Abstract [en]

    The process of resonance assignment is fundamental to most NMR studies of protein structure and dynamics. Unfortunately, the manual assignment of residues is tedious and time-consuming, and can represent a significant bottleneck for further characterization. Furthermore, while automated approaches have been developed, they are often limited in their accuracy, particularly for larger proteins. Here, we address this by introducing the software COMPASS, which, by combining automated resonance assignment with manual intervention, is able to achieve accuracy approaching that from manual assignments at greatly accelerated speeds. Moreover, by including the option to compensate for isotope shift effects in deuterated proteins, COMPASS is far more accurate for larger proteins than existing automated methods. COMPASS is an open-source project licensed under GNU General Public License and is available for download from http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en. Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.

  • 246.
    Niklasson, Markus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Andrésen, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Helander, Sara
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Roth, Marie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Zimdahl Kahlin, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Mårtensson, Lars-Göran
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Robust and convenient analysis of protein thermal and chemical stability2015In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 24, no 12, p. 2055-2062Article in journal (Refereed)
    Abstract [en]

    We present the software CDpal that is used to analyze thermal and chemical denaturation data to obtain information on protein stability. The software uses standard assumptions and equations applied to two-state and various types of three-state denaturation models in order to determine thermodynamic parameters. It can analyze denaturation monitored by both circular dichroism and fluorescence spectroscopy and is extremely flexible in terms of input format. Furthermore, it is intuitive and easy to use because of the graphical user interface and extensive documentation. As illustrated by the examples herein, CDpal should be a valuable tool for analysis of protein stability.

  • 247.
    Niklasson, Markus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Otten, Renee
    Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA, USA..
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Andrésen, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Schlagnitweit, Judith
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Petzold, Katja
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Comprehensive analysis of NMR data using advanced line shape fitting.2017In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 69, no 2, p. 93-99Article in journal (Refereed)
    Abstract [en]

    NMR spectroscopy is uniquely suited for atomic resolution studies of biomolecules such as proteins, nucleic acids and metabolites, since detailed information on structure and dynamics are encoded in positions and line shapes of peaks in NMR spectra. Unfortunately, accurate determination of these parameters is often complicated and time consuming, in part due to the need for different software at the various analysis steps and for validating the results. Here, we present an integrated, cross-platform and open-source software that is significantly more versatile than the typical line shape fitting application. The software is a completely redesigned version of PINT ( https://pint-nmr.github.io/PINT/ ). It features a graphical user interface and includes functionality for peak picking, editing of peak lists and line shape fitting. In addition, the obtained peak intensities can be used directly to extract, for instance, relaxation rates, heteronuclear NOE values and exchange parameters. In contrast to most available software the entire process from spectral visualization to preparation of publication-ready figures is done solely using PINT and often within minutes, thereby, increasing productivity for users of all experience levels. Unique to the software are also the outstanding tools for evaluating the quality of the fitting results and extensive, but easy-to-use, customization of the fitting protocol and graphical output. In this communication, we describe the features of the new version of PINT and benchmark its performance.

  • 248.
    Nilsson, Peter
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Joshi-Barr, Shivanjali
    University of California San Diego.
    Winson, Olivia
    University of California San Diego.
    Sigurdson, Christina J
    University of California San Diego.
    Prion Strain Interactions Are Highly Selective2010In: JOURNAL OF NEUROSCIENCE, ISSN 0270-6474, Vol. 30, no 36, p. 12094-12102Article in journal (Refereed)
    Abstract [en]

    Various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. Here we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with (1) no interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a second (interference). The hybrid plaques were maintained on additional passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions but also directly demonstrate interactions that may occur in other protein aggregate mixtures.

  • 249.
    Nilsson, Peter
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Hammarstrom, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    A pentameric luminescent-conjugated oligothiophene for optical imaging of in vitro-formed amyloid fibrils and protein aggregates in tissue sections.2012In: Methods in molecular biology (Clifton, N.J.), ISSN 1940-6029, Vol. 849, p. 425-434Article in journal (Refereed)
    Abstract [en]

    Luminescent-conjugated oligo- and polythiophenes (LCOs and LCPs) are valuable tools for optical imaging of a plethora of protein aggregates associated with amyloidoses. Here, we describe the utilization of an anionic pentameric LCO, p-FTAA, for staining of protein aggregates in a variety of platforms, including in vitro-formed amyloid fibrils and tissue sections.

  • 250.
    Nilsson, Peter
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Department of Physics, The Norwegian University of Science and Technology, 7491, Trondheim, Norway.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues2018In: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, p. 485-496Chapter in book (Refereed)
    Abstract [en]

    Luminescent-conjugated oligo- and polythiophenes (LCOs and LCPs) are valuable tools for optical imaging of a plethora of protein aggregates associated with amyloidoses. Here, we outline updated protocols for the application of the anionic pentameric LCO, p-FTAA, for staining and hyperspectral imaging of protein aggregates in a variety of settings such as in vitro formed amyloid fibrils, ex vivo tissue sections, and whole brain Drosophila.

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