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| 2. |
- Olofsson, Anders, et al.
(författare)
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Probing solvent accessibility of transthyretin amyloid by solution NMR spectroscopy.
- 2004
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Ingår i: J Biol Chem. - 0021-9258. ; 279:7, s. 5699-707
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Tidskriftsartikel (refereegranskat)abstract
- The human plasma protein transthyretin (TTR) may form fibrillar protein deposits that are associated with both inherited and idiopathic amyloidosis. The present study utilizes solution nuclear magnetic resonance spectroscopy, in combination with hydrogen/deuterium exchange, to determine residue-specific solvent protection factors within the fibrillar structure of the clinically relevant variant, TTRY114C. This novel approach suggests a fibril core comprised of the six beta-strands, A-B-E-F-G-H, which retains a native-like conformation. Strands C and D are dislocated from their native edge region and become solvent-exposed, leaving a new interface involving strands A and B open for intermolecular interactions. Our results further support a native-like intermolecular association between strands F-F' and H-H' with a prolongation of these beta-strands and, interestingly, with a possible shift in beta-strand register of the subunit assembly. This finding may explain previous observations of a monomeric intermediate preceding fibril formation. A structural model based on our results is presented.
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| 3. |
- Andersson, Karin, et al.
(författare)
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Only amyloidogenic inermediates of transthyretin induce apoptosis
- 2002
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Carolina Academic Press. - 0006-291X .- 1090-2104. ; 294:2, s. 309-314
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Tidskriftsartikel (refereegranskat)abstract
- In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism.
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| 4. |
- Borg, Mikael, et al.
(författare)
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Structure and formation of the Al(100)-(root 5 x root 5) R27 degrees-Na phase: a LEED, DFT and HRCLS study
- 2002
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Ingår i: Surface Science. - 0039-6028. ; 515:2-3, s. 267-280
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Tidskriftsartikel (refereegranskat)abstract
- Adsorption of 0.2 ML Na on Al(1 0 0) at room temperature yields a disordered Al(1 0 0)-(1 x 1)-Na phase, which transforms reversibly to a well-ordered Al(1 0 0)-(root5 x root5)R27degrees-Na phase on cooling below 250 K. Based on low energy electron diffraction (LEED) and high resolution core-level spectroscopy (HRCLS) measurements, and on ab initio calculations, it is concluded that the structure of the Al(1 0 0)-(root5 x root5-)R27degrees-Na phase consists of Na atoms occupying substitutional sites. The structural parameters obtained from LEED and density functional theory analyses are in quantitative agreement. Adsorption of 0.2 ML Na at 100 K yields an Al(1 0 0)-c(2 x 2)-Na island structure, which transforms irreversibly into the (root5 x root5)R27degrees-Na structure by annealing above 190 K. The nature of the reversible and irreversible phase transformations to the (root5 x root5)R27degrees structure is investigated by HRCLS and LEED. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 5. |
- Borga, M, et al.
(författare)
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Structure and dynamics of Na adsorption on Al(100)
- 2002
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Ingår i: 7th International Conference on Nanometer-Scale Science and Technology and 21st European Conference on Surface Science.
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Konferensbidrag (refereegranskat)abstract
- The adsorption of 0.2 monolayers (ML) of Na on Al(100) has been studied both experimentally, using low energy electron diffraction (LEED) and high resolution core level spectroscopy (HRCLS), and theoretically, using density functional theory (DFT). Two ordered phases are found: Islands of c (2×2) symmetry with Na atoms occupying four-fold hollow sites result from low temperature deposition and a (√5×√5)R27° structure with Na in surface substitutional sites is formed by annealing of the low temperature island structure at 300 K and subsequent cooling below 230 K. The (√5×√5)R27° structure undergoes a reversible order-disorder phase transition at ~230 K. To investigate this phase transition further, we performed additional DFT calculations for a wide range of coverages (from 0.0625 to 0.5 ML), for adsorption in both hollow and substitutional sites, from which we extract interaction energies which are used in a lattice gas Monte Carlo simulations
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| 6. |
- Borgström, Magnus, et al.
(författare)
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Spontaneous InAs quantum dot nucleation at strained InP/GaInAs interfaces
- 2003
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 83:23, s. 4830-4832
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Tidskriftsartikel (refereegranskat)abstract
- We present a cross-sectional scanning-tunneling microscopy investigation of twofold stacked InAs quantum dots in InP, between layers of GaInAs. The dots are vertically aligned, and images with atomic resolution show that the dots consist of pure InAs. Despite the intended twofold stacking of dots, three dots were often found in the stacks. The third dot formed immediately on top of the final InP layer, at the InP/GaInAs interface. Atomically resolved images of these spontaneously formed dots indicate that they also consist of pure InAs. The effect is discussed in terms of phase segregation of GaInAs and arsenic-phosphorus exchange reactions. (C) 2003 American Institute of Physics.
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| 7. |
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| 8. |
- Eneqvist, Therese, et al.
(författare)
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Disulfide-bond formation in the transthyretin mutant Y114C prevents amyloid fibril formation in vivo and in vitro.
- 2002
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Ingår i: Biochemistry. - 0006-2960. ; 41:44, s. 13143-51
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Tidskriftsartikel (refereegranskat)abstract
- The Y114C mutation in human transthyretin (TTR) is associated with a particular form of familial amyloidotic polyneuropathy. We show that vitreous aggregates ex vivo consist of either regular amyloid fibrils or disordered disulfide-linked precipitates that maintain the ability to bind Congo red. Furthermore, we demonstrate in vitro that the ATTR Y114C mutant exists in three forms: one unstable but nativelike tetrameric form, one highly aggregated form in which a network of disulfide bonds is formed, and one fibrillar form. The disulfide-linked aggregates and the fibrillar form of the mutant can be induced by heat induction under nonreduced and reduced conditions, respectively. Both forms are recognized by the amyloid specific antibody MAB(39-44). In a previous study, we have linked exposure of this epitope in TTR to a three-residue shift in beta-strand D. The X-ray crystallographic structure of reduced tetrameric ATTR Y114C shows a structure similar to that of the wild type but with a more buried position of Cys10 and with beta-mercaptoethanol associated with Cys114, verifying the strong tendency for this residue to form disulfide bonds. Combined with the ex vivo data, our in vitro findings suggest that ATTR Y114C can lead to disease either by forming regular unbranched amyloid fibrils or by forming disulfide-linked aggregates that maintain amyloid-like properties but are unable to form regular amyloid fibrils.
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| 9. |
- Eneqvist, Therese, et al.
(författare)
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The beta-slip: a novel concept in transthyretin amyloidosis.
- 2000
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Ingår i: Mol Cell. - 1097-2765. ; 6:5, s. 1207-18
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Tidskriftsartikel (refereegranskat)abstract
- Transthyretin is a tetrameric plasma protein associated with two forms of amyloid disease. The structure of the highly amyloidogenic transthyretin triple mutant TTRG53S/E54D/L55S determined at 2.3 A resolution reveals a novel conformation: the beta-slip. A three-residue shift in beta strand D places Leu-58 at the position normally occupied by Leu-55 now mutated to serine. The beta-slip is best defined in two of the four monomers, where it makes new protein-protein interactions to an area normally involved in complex formation with retinol-binding protein. This interaction creates unique packing arrangements, where two protein helices combine to form a double helix in agreement with fiber diffraction and electron microscopy data. Based on these findings, a novel model for transthyretin amyloid formation is presented.
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| 10. |
- Fors, Hjalmar, 1971-
(författare)
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Mutual Favours : The social and scientific practice of eighteenth-century Swedish chemistry
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dissertation is a study of the creation of chemistry as a science in eighteenth-century Sweden. It is argued that the chemists in the study participated in a network for exchange of scientific facts and all kinds of favours, in which science was both conducted, negotiated and created. A number of relationships between chemists are analyzed with regards to two central eighteenth-century institutions: the patron-client relationship and the egalitarian ideal of reciprocity articulated in the eighteenth-century Republic of Letters.In the first half the background to the success of Swedish chemistry is sketched out. It is discussed which groups supported chemistry and for what reasons. There is a discussion of the theoretical and methodological changes that were initiated by Torbern Bergman when he took over the chair of chemistry in Uppsala. Bergman's attempts to marginalize his two major opponents, Johan Gottschalk Wallerius, the previous holder of the Uppsala chair and Gustav von Engeström, the head of the Board of Mines laboratory in Stockholm, are also analyzed.In the second half the focus shifts to the interaction of university chemistry with industry. It is shown how industrial processes gradually came to be redefined as a kind of “coarse chemistry”, a process which benefited both engineers employed at industrial installations and university chemists. The many themes explored in the study are brought together in an analysis of Carl Wilhelm Scheele’s adoption into the network of Swedish chemists. The dissertation concludes with a survey of the more general conclusions.
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