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  • 1
    Publication Date: 2018-01-24
    Description: The accumulation of misfolded proteins (MP), both unique and common, for different diseases is central for many chronic degenerative diseases. In certain patients MP accumulation is systemic (e.g. TTR amyloid) and in others this is localized to a specific cell type (e.g. Alzheimer's disease). In neurodegenerative diseases, NDs, it is noticeable that the accumulation of MP progressively spreads throughout the nervous system. Our main hypothesis of this article is that MPs are not only markers but also active carriers of pathogenicity. Here, we discuss studies from comprehensive molecular approaches aimed at understanding MP conformational variations (polymorphism) and their bearing on spreading of MPs, MP toxicity, as well as MP targeting in imaging and therapy. Neurodegenerative disease (ND) represents a major and growing societal challenge, with millions of people worldwide suffering from Alzheimer's or Parkinson's diseases alone. For all NDs, current treatment is palliative without addressing the primary cause, and is not curative. Over recent years particularly the shape-shifting properties of misfolded proteins and their spreading pathways have been intensively researched. The difficulty in addressing ND has prompted most major pharma companies to severely downsize their nervous system disorder research. Increased academic research is pivotal for filling this void and to translate basic research into tools for medical professionals. Recent discoveries of targeting drug design against MPs and improved model systems to study structure, pathology spreading and toxicity strongly encourage future studies along these lines to provide an opportunity for selective imaging, prognostic diagnosis, and therapy. This article is protected by copyright. All rights reserved.
    Print ISSN: 0954-6820
    Electronic ISSN: 1365-2796
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 2
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Sedimentation coefficients, s0c, diffusion coefficients, Dc, and specific viscosities have been determined for eleven samples of commercial narrow-molecular-weight distribution polystyrenes Pressure Chemicals Co. and Waters Ass., 5 · 104 g · mol-1 〈 weight average molecular weight Mw 〈 2 · 106 g · mol-1 at different concentrations in toluene (25°C). From the Svedberg equation the values of the MsD averages have been calculated from the sedimentation and diffusion coefficients extrapolated to infinite dilution. The reproducibility of the measured values of s00, D0 and [η] was better than 3%. The parameters determined for the same samples in Prague and in Uppsala (using different instruments and different data evaluation techniques) were in good agreement (the maximum deviation 6%). The plots of log s00 vs. log D0 and log [η] vs. MsD are linear without any systematic deviations; all experimental hydrodynamic data are consistent within the interval of experimental error, i.e. ±3%. However, when plotted versus the nominal molecular weights the scatter is considerably increased. Furthermore, the calculated average molecular weights, MsD, differ in several instances from the nominal ones.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The thermally induced inverted helix-coil transition of poly(γ-benzyl-L-glutamate) (M̄w ≈ 320 000) in a mixture of dichloroacetic acid/1,2-dichloroethane (80/20 w/w) has been observed by the temperature dependence of both the refractive index increment and the partial specific volume; the transition is centered around 31°C. A correlation of the refractive index increment and the partial specific volume data, utilizing an equation based on the Onsager-Böttcher theory, had no significant success.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Sedimentation measurements over the concentration interval 3-16 kg. m-3 and the pressure range 0,1-5 MPa are reported for the system polyisobutylene/octane. The pressure influence on the sedimentation process was found to be less pronounced at higher than at lower concentrations.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Accurate measurements of the sedimentation coefficients at unit pressure and zero-concentration s00, the diffusion coefficients at zero concentration D0, and the intrinsic viscosities [η] were conducted at theta-conditions (cyclohexane, 34,5°C) on 11 polystryrene standard samples with narrow molar mass distribution. These samples with nominal mass-average molar masses (5 · 104 〈 Mw 〈 2 · 106 g · mol-1), provided by three manufacturers for the use as calibration standards, were the same as in the previous paper of this series summarizing our measurements in toluene. Logarithmic correlations between s00, D0 and [η] are linear with deviations lower than ± 3% and indicate good consistency of all three independent sets of measured quantities. The molar masses MsD as determined from s00 and D0 by means of the Svedberg equation are in very good accordance with those previously determined in toluene, but for most samples the MsD are lower than the nominal values Mw as given by the manufacturers. For some standards the deviations amount to 15-35% and cannot be explained by experimental errors or by the polydispersity of the samples. On the other hand, two pairs of standards exhibit the same values of s00, D0 and [η] in both solvents, although the nominal molar masses differ by 20%. These results lead to the conclusion that the experimentally determined MsD values are more reliable characteristics of the standard samples than the nominal Mw values and that the sedimentation-diffusion technique is a powerful, though laborious, tool for an absolute determination of the molar mass.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Isotactic polystyrene samples crystallized from concentrated solutions (〉 10% by weight) in the thermodynamically good solvent toluene display a lamellar thickness L = (170 ± 15) Å at room temperature, as determined by neutron scattering investigation. This thickness is about twice the value reported for samples crystallized in poor solvents. The results may be interpreted in terms of a substantially smaller melting enthalpy of the polymer in toluene, producing a proportionally inverse increase of the thickness L̄c of the central, crystalline portion of the lamellae. In turn, we suggest that the overall thickness L of the lamellae increases more than proportionally with L̄c, due to the need of accomodating in the amorphous zone increasing amounts of polymer containing steric defects. The decrease of the melting enthalpy is also qualitatively consistent with growth rate results. The half-peak width of the Bragg diffraction peaks suggests that the crystalline fraction of the lamellar thickness is about 50%, in approximate agreement with results obtained by Overbergh, Berghmans and Reynaers (J. Polym. Sci., Polym. Phys. Ed. 14, 1177 (1976)) from bulk-crystallized samples showing about the same values of L and L̄c as observed by us.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0021-8383
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 26 (1981), S. 3385-3393 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Measurements of relaxation times, T1 and T2, and self-diffusion coefficients, D, for small molecules, viz., H2O, dioxane and t-butanol, in the gel system cellulose/H2O are reported and compared with those for H2O in a polyacrylamide gel of the same polymer content. The temperature dependence of T1 and D can for all the penetrants be represented by Arrhenius type relations which merely are parallel shifts by the same amount, towards smaller values, of those obtained without polymer. The T2 values for H2O in both gels pass through a shallow minimum over the considered temperature interval (14°-44°C). Furthermore, relaxation times T1 of D2O in the gel system cellulose/D2O are reported; in a plot of ln T1 vs. 1/T, a plateau region is observed at higher temperatures.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0098-1273
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Sedimentation velocity data on polystyrene in a good solvent (toluene) and in a theta solvent (cyclopentane), over a large concentration range are reported. Under good-solvent conditions the exponent β in the apparent scaling law describing the concentration dependence of the sedimentation coefficient (s ∝ cβ) in the semidiiute region is found to be concentration dependent. However, a power law fit to data for the highest molecular weight (M = 20.6 × 106) in the concentration region (c 〈 2 kg m-3) yields a value β = -0.59, somewhat smaller than that (-0.54) predicted theoretically. This discrepancy and the observed curvature in logs vs. logc at higher concentrations are discussed. Under theta-solvent conditions, on the other hand, the concentration dependence of s in the semidilute regime can be represented by a simple power law, with β = -1.0, in excellent agreement with the theoretical prediction. The crossover concentration c*, separating the dilute and semidilute concentration regimes, was found to be well defined and located at c = 1/[η]. c* varies with molecular weight as M-0.73 and M-0.50 under good-solvent and theta-solvent conditions, respectively.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0098-1273
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The refractive index increment of macromolecules in solution has been observed to be a function of concentration, temperature, molecular weight, wavelength of light, and solvent. Most of the studies have been performed in dilute or semidilute solutions, and therefore the concentration dependence of the refractive index increment was too small to be accurately observed. This study was performed on solutions of polystyrene in trans-decalin at mass fractions, w2, from 0.01 to 0.11 and at 436 and 546 nm wavelengths. The concentration and temperature dependence of the refractive index increment were measured, and comparisons were made with previous theories.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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