| 1. |
- Girard, R T, et al.
(författare)
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Electronic structure of ZnO(0001) studied by angle-resolved photoelectron spectroscopy
- 1997
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Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 373:2-3, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of the ZnO(0001) surface was studied by angle-resolved photoelectron spectroscopy. The recorded normal emission spectra give information about the Valence band states as well as the Zn 3d states. The dispersions of the four valence bands observed in the (0001) direction were compared with theory and are in good agreement with recent calculations which consider the Zn 3d electrons as part of the valence band. The Zn 3d states are seen to separate into two groups of four and six bands, which show dispersion with k(perpendicular to). This is in agreement with theoretical results but the location of these states were not accurately predicted. The present photoemission results show that they lie around 10.5 eV below E(F). Two surface states were observed on the (0001) surface. One, at 7.5 eV binding energy, was predicted by theory and is interpreted as arising from the ''back-bondings'' of the Zn 4s-O 2p mixed bulk states. The other one at 4.5 eV below E(F), most likely Zn 4p-0 2p derived, was not predicted by theoretical calculations and this is discussed further in the text. (C) 1997 Elsevier Science B.V.
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| 2. |
- Nylén, H., et al.
(författare)
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O KVV Auger emission versus resonant photoemission at the O K edge of high-Tc superconductors
- 1998
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Ingår i: Physica C: Superconductivity and its Applications. - 0921-4534. ; 300:3-4, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- Photoelectron spectroscopy results on single crystals of the superconductors Bi2Sr2CaCu2O8,Bi2Sr 2CuO6, Ba0.6K0.4BiO3 and the semiconductor Ba0.9K0.1BiO3 are reported for the photon energy region around the O K absorption threshold. The development of the O-KVV Auger structure has been carefully monitored as a function of photon energy. A non-monotonic behavior displaying a feature at a constant binding energy of about 14 eV was found for Bi2Sr2CaCu2O8 and Bi2Sr2CuO6 in a narrow photon energy region of 1 eV at the main edge of the O K absorption spectrum around 530 eV. The corresponding enhancement, connected with the autoionization of O 2 p states, is absent in Ba1-xKxBiO3 in contrast to Bi2Sr2CaCu2O8 and Bi2Sr2CuO6. The resonant enhancement is more pronounced for Bi2Sr2CuO6 as compared to Bi2Sr2CaCu2O8, which can be explained by a lower charge carrier concentration in the former case, leading to a more localized nature of intermediate O 2 p states. The model parameters Cu d-d and O p-p Coulomb interactions and the charge transfer energy Δ are estimated from the experiments.
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| 3. |
- Qvarford, M, et al.
(författare)
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Photoemission and x-ray absorption study of superconducting and semiconducting Ba1-xKxBiO3 single crystals
- 1996
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 54:9, s. 6700-6707
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Tidskriftsartikel (refereegranskat)abstract
- Semiconducting Ba0.9K0.1BiO3 and superconducting Ba0.6K0.4BiO3 single crystals cleaved in situ have been studied by core level and valence band photoelectron spectroscopy and O K edge x-ray absorption spectroscopy. It was found that the general shape of the valence band spectrum agrees with the shape predicted by band structure calculations, but the intensity near the Fermi level, was lower in the experimental spectrum as compared to the calculated. The O K edge spectra showed that the metallic phase is not related to the presence of doping inducted O 2p holes. This property of Ba1-xKxBiO3 shows that the semiconductor-metal transition of this system is of a different nature than that of the hole doped cuprate high-T-c superconductors. The core level photoemission spectra of the cations showed a small asymmetry for Ba0.9K0.1BiO3. Corresponding spectra for Ba0.6K0.4BiO3 showed a larger asymmetry resulting in a resolved high binding energy shoulder in the Bi 4f spectrum. The origin of this feature is discussed.
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| 4. |
- Qvarford, M., et al.
(författare)
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X-ray absorption study of oxygen in the high-Tc superconductor Bi2Sr2CaCu2O8 near the interfaces to Cu, Ag and Au
- 1996
-
Ingår i: Physica C: Superconductivity and its Applications. - : Elsevier BV. - 0921-4534 .- 1873-2143. ; 265:1-2, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- The influence on O 2p holes in single crystalline Bi2Sr2CaCu2O8 upon the interface formation to Cu, Ag and Au has been studied by O K edge X-ray absorption measurements. It was found that Cu reduces the amount of doping induced O 2p holes significantly in the vicinity of the interface, whereas Ag and Au gave a much smaller reduction of these states. Photoemission spectra confirmed previous findings that Cu causes a strong chemical reaction at the Bi-O surface of Bi2Sr2CaCu2O8, in contrast to Ag and Au which induced only a minimal reaction. The results support the opinion that the Bi-O layers are essential for the doping of the Cu-O2 layers in Bi2Sr2CaCu2O8.
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| 5. |
- TJERNBERG, O, et al.
(författare)
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ANGLE-RESOLVED PHOTOEMISSION ON NIO - ON THE NATURE OF THE VALENCE-BAND
- 1995
-
Ingår i: Vacuum. - 0042-207X .- 1879-2715. ; 46:8-10, s. 1215-1218
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Tidskriftsartikel (refereegranskat)abstract
- Angle resolved photoelectron spectroscopy has been performed on the valence band of NiO at the National Swedish Laboratory for Synchrotron Radiation. Normal emission spectra have been recorded for photon energies between 17 and 140 eV in order to study the electronic structure of the valence band. The experimentally determined band structure has been compared with a local density augmented plane wave band structure calculation. Signs of the influence of antiferromagnetic ordering are found and the general agreement between experimental and theoretical oxygen derived bands indicates strong hybridization between Ni 3d and O 2p orbitals.
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| 6. |
- Tjernberg, O, et al.
(författare)
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Evidence of pseudogap related core level shifts in Bi2Sr2Ca1-xYxCu2O8+delta
- 1997
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 79:3, s. 499-502
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Tidskriftsartikel (refereegranskat)abstract
- Photoelectron spectroscopy data from Bi2Sr2Ca1-xYxCu2O8+delta Single crystals, for x = 0, 0.16, and 0.55, are presented. It is shown that there are core level shifts related to the opening of a pseudogap and that similar shifts are observed at the opening of the superconducting gap in optimally doped samples. This result is in agreement with pair formation above T-c as suggested by V.J. Emery and S.A. Kivelson [Nature (London) 374, 434 (1995)].
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| 7. |
- Tjernberg, O, et al.
(författare)
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Influence of magnetic ordering on the NiO valence band
- 1996
-
Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 54:15, s. 10245-10248
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Tidskriftsartikel (refereegranskat)abstract
- The influence of magnetic ordering on the NiO valence band has been studied by angle resolved photoelectron spectroscopy. Measurements have been performed at temperatures above and below the Neel temperature (T-N), as well as at room. temperature. The results show temperature dependence but no significant changes in the valence band structure are detected in connection to the passing of T-N. The reported data suggest that the magnetic phase transition does not influence the valence band structure significantly.
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| 8. |
- Tjernberg, O, et al.
(författare)
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Resonant photoelectron spectroscopy on NiO
- 1996
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 53:15, s. 10372-10376
-
Tidskriftsartikel (refereegranskat)abstract
- Resonant photoelectron spectroscopy studies have been performed on the NiO valence band at photon energies corresponding to the Ni 2p, 3p, and O 1s absorption thresholds. Strong resonances are seen in the vicinity of the Ni 2P threshold, which confirm earlier conclusions from the weaker resonances seen at the Ni 3p threshold. No valence-band resonance is observed at the O 1s threshold. The analysis of this data confirms the picture of NiO as a strongly correlated charge-transfer insulator by identifying the highest-lying states as being of mainly 3d(8)L final-state character. The existence of localized excited Ni states, as well as the delocalized nature of the O states, are confirmed. Comparisons with the configuration-interaction model and quasiparticle calculations are also made.
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| 9. |
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| 10. |
- Chang, J., et al.
(författare)
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Anisotropic breakdown of Fermi liquid quasiparticle excitations in overdoped La2-xSrxCuO4
- 2013
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2559-
-
Tidskriftsartikel (refereegranskat)abstract
- High-temperature superconductivity emerges from an un-conventional metallic state. This has stimulated strong efforts to understand exactly how Fermi liquids breakdown and evolve into an un-conventional metal. A fundamental question is how Fermi liquid quasiparticle excitations break down in momentum space. Here we show, using angle-resolved photoemission spectroscopy, that the Fermi liquid quasiparticle excitations of the overdoped superconducting cuprate La1.77Sr0.23CuO4 is highly anisotropic in momentum space. The quasiparticle scattering and residue behave differently along the Fermi surface and hence the Kadowaki-Wood's relation is not obeyed. This kind of Fermi liquid breakdown may apply to a wide range of strongly correlated metal systems where spin fluctuations are present.
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| 11. |
- Elmberg, Johan, et al.
(författare)
-
Nötkråka
- 2007
-
Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Elmberg, Johan, et al.
(författare)
-
Nötkråka
- 2007
-
Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Fatuzzo, C. G., et al.
(författare)
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Nodal Landau Fermi-liquid quasiparticles in overdoped La1.77Sr0.23CuO4
- 2014
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 89:20, s. 205104-
-
Tidskriftsartikel (refereegranskat)abstract
- Nodal angle-resolved photoemission spectra taken on overdoped La1.77Sr0.23CuO4 are presented and analyzed. It is proven that the low-energy excitations are true Landau Fermi-liquid quasiparticles. We show that momentum and energy distribution curves can be analyzed self-consistently without quantitative knowledge of the bare band dispersion. Finally, by imposing Kramers-Kronig consistency on the self-energy Sigma, insight into the quasiparticle residue is gained. We conclude by comparing our results to quasiparticle properties extracted from thermodynamic, magnetoresistance, and high-field quantum oscillation experiments on overdoped Tl2Ba2CuO6+delta.
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| 14. |
- Frykman, Susanne, et al.
(författare)
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Synaptic and Endosomal Localization of Active gamma-Secretase in Rat Brain
- 2010
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:1, s. e8948-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA key player in the development of Alzheimer's disease (AD) is the gamma-secretase complex consisting of at least four components: presenilin, nicastrin, Aph-1 and Pen-2. gamma-Secretase is crucial for the generation of the neurotoxic amyloid beta-peptide (A beta) but also takes part in the processing of many other substrates. In cell lines, active gamma-secretase has been found to localize primarily to the Golgi apparatus, endosomes and plasma membranes. However, no thorough studies have been performed to show the subcellular localization of the active gamma-secretase in the affected organ of AD, namely the brain.Principal FindingsWe show by subcellular fractionation of rat brain that high gamma-secretase activity, as assessed by production of A beta 40, is present in an endosome-and plasma membrane-enriched fraction of an iodixanol gradient. We also prepared crude synaptic vesicles as well as synaptic membranes and both fractions showed high A beta 40 production and contained high amounts of the gamma-secretase components. Further purification of the synaptic vesicles verified the presence of the gamma-secretase components in these compartments. The localization of an active gamma-secretase in synapses and endosomes was confirmed in rat brain sections and neuronal cultures by using a biotinylated gamma-secretase inhibitor together with confocal microscopy.SignificanceThe information about the subcellular localization of gamma-secretase in brain is important for the understanding of the molecular mechanisms of AD. Furthermore, the identified fractions can be used as sources for highly active gamma-secretase.
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| 15. |
- Gao, Yang, et al.
(författare)
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Live Cell FRET Imaging Reveals Amyloid beta-Peptide Oligomerization in Hippocampal Neurons
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:9
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid beta-peptide (A beta) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of A beta oligomerization in neurons still need to be revealed. Forster resonance energy transfer (FRET) is a simple but effective way to study molecular interactions. Here, we used a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detected A beta 42 oligomerization in primary neurons. The neurons were incubated with fluorescently labeled A beta 42 in the cell culture medium for 24 h. A beta 42 were internalized and oligomerized in the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of A beta 42 were significantly higher than for A beta 40. These findings provide a better understanding of A beta 42 oligomerization in neurons.
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| 16. |
- Gaunitz, Stefan, et al.
(författare)
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The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease
- 2021
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 159:2, s. 292-304
-
Tidskriftsartikel (refereegranskat)abstract
- Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation. Still, the roles of glycans in the development of AD are relatively unexplored. Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls. As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain. Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain. Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain. All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc). The glycans that were altered in AD brain differed from those that were altered in AD CSF. One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid. Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies. (Figure presented.).
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| 17. |
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| 18. |
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| 19. |
- Grishin, Michael A., et al.
(författare)
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Anisotropy of electron structure at InAs(111) surfaces by laser pump-and-probe photoemission spectroscopy
- 2005
-
Ingår i: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 574:1, s. 89-94
-
Tidskriftsartikel (refereegranskat)abstract
- The electronic structure and the electron dynamics of the clean InAs(111)A 2 x 2 and the InAs(111)B 1 x 1 surfaces have been studied by laser pump-and-probe photoemission spectroscopy. Normally unpopulated electron states above the valence band maximum (VBM) are filled on the InAs(111)A surface due to the conduction band pinning above the Fermi level (E-F). Accompanied by the downward band banding alignment, a charge accumulation layer is confined to the surface region creating a two dimensional electron gas (2DEG). The decay of the photoexcited carriers above the conduction band minimum (CBM) is originated by bulk states affected by the presence of the surface. No occupied states were found on the InAs(111)B 1 x 1 surface. This fact is suggested to be due to the surface stabilisation by the charge removal from the surface into the bulk. The weak photoemission intensity above the VBM on the (111)B surface is attributed to electron states trapped by surface defects. The fast decay of the photoexcited electron states on the (111)A and the (111)B surfaces was found to be tau(111A) less than or equal to 5 ps and tau(111B) less than or equal to 4ps, respectively. We suggest the diffusion of the hot electrons into the bulk is the decay mechanism. (
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| 20. |
- Haytural, Hazal, et al.
(författare)
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Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis
- 2021
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
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| 21. |
- Horio, M., et al.
(författare)
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Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates
- 2018
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:7
-
Tidskriftsartikel (refereegranskat)abstract
- We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k(z) dispersion is observed along the nodal direction, whereas a significant antinodal k(z) dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La2-xSrxCuO4 cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.
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| 22. |
- Janin, E., et al.
(författare)
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Corrosive adsorption of Sn on the Pt(110)(1 x 2) surface
- 2002
-
Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 515:03-feb, s. 462-470
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Tidskriftsartikel (refereegranskat)abstract
- Room temperature deposition of Sn on the Pt(110)(1 x 2) surface has been studied by scanning tunnelling microscopy and core level photoelectron spectroscopy. At low coverage Sri is found in three different configurations; as mobile adatoms in the valley of the missing-row reconstruction, as 1D-Pt-Sn-Pt- alloy chains forming local Pt3Sn(110)2 x 2 regions and finally as 3D alloy islands. At higher coverage these islands form a platinum rich alloy film, which is dissolved in the crystal upon annealing to 600 degreesC.
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| 23. |
- Jayamanne, M, et al.
(författare)
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Development of a two-dimensional liquid chromatography system for isolation of drug metabolites
- 2010
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 51:3, s. 649-657
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Tidskriftsartikel (refereegranskat)abstract
- The separation, isolation and identification of drug metabolites from complex endogenous matrices like urine, plasma and tissue extracts are challenging tasks. Metabolites are usually first identified by mass spectrometry and tentative structures proposed from product ion spectra. In many cases mass spectrometry cannot be used to determine positional isomers and metabolites have to be fractionated in microgram amounts for analysis by NMR. To overcome the difficulties associated with separation and isolation of drug metabolites from biological matrices, a new two-dimensional liquid chromatography system has been developed. The retention times of 45 acidic, basic and neutral compounds were determined on liquid chromatographic columns with different stationary phases in order to identify two columns with highly different selectivity to be used for two-dimensional liquid chromatography. Drug metabolites of three model compounds were first generated in vitro with liver microsomes and then compared with potential metabolites formed by oxidation with hydrogen peroxide catalyzed by meso-tetra (4-sulphonatophenyl) porphine (porphine). The results showed that the porphine system could be used as a complementary system for the generation of phase I microsomal metabolites with high yield of some metabolites in a less complex matrix. The two-dimensional liquid chromatography system was used to separate and isolate microsomal and porphine generated drug metabolites in off-line and on-line mode. Finally, to verify the utility of the developed system, urine samples were spiked with metabolite standards of model compounds for separation in the two-dimensional system. Excellent separations were obtained with an amide column in the first dimension and a pentafluorophenylpropyl (PFPP) column in the second dimension. The metabolites were successfully separated from each other as well as from the complex biological matrix. The results demonstrate the applicability of the system for fractionation of drug metabolites but it could also be used in many other analytical purposes, especially for basic compounds. Trace levels of metabolites were successfully separated in the on-line mode which failed in the off-line mode.
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| 24. |
- Keller, Lina, et al.
(författare)
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The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of A beta in different brain regions
- 2010
-
Ingår i: European Journal of Human Genetics. - London : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 18:11, s. 1202-1208
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Tidskriftsartikel (refereegranskat)abstract
- Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid beta-peptide (A beta) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that A beta 42 is a major player in the etiology of AD. Here, we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of AD. We also performed an extensive investigation on the concentration and distribution of A beta species of different lengths in six brain regions from two mutation carriers. Our study showed that A beta 42 and a longer peptide, A beta 43, were present both in plaque cores and in total amyloid preparations, and were each clearly more frequent than A beta 40 in all examined regions, as shown by both mass spectrometry and immunohistochemistry. European Journal of Human Genetics (2010) 18, 1202-1208; doi: 10.1038/ejhg.2010.107; published online 14 July 2010
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| 25. |
- Larsson, Annika, et al.
(författare)
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Unwinding fibril formation of medin, the peptide of the most common form of human amyloid.
- 2007
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 361:4, s. 822-828
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Tidskriftsartikel (refereegranskat)abstract
- Medin amyloid affects the medial layer of the thoracic aorta of most people above 50 years of age. The consequences of this amyloid are not completely known but the deposits may contribute to diseases such as thoracic aortic aneurysm and dissection or to the general diminished elasticity of blood vessels seen in elderly people. We show that the 50-amino acid residue peptide medin forms amyloid-like fibrils in vitro. With the use of Congo red staining, Thioflavin T fluorescence, electron microscopy, and a solid-phase binding assay on different synthetic peptides, we identified the last 18-19 amino acid residues to constitute the amyloid-promoting region of medin. We also demonstrate that the two C-terminal phenylalanines, previously suggested to be of importance for amyloid formation, are not required for medin amyloid formation.
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| 26. |
- Lundgren, Jolanta L, et al.
(författare)
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Activity-independent release of the amyloid β-peptide from rat brain nerve terminals.
- 2014
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 566:Mar 3, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid β-peptide (Aβ). The exact localization of the production of Aβ and the mechanisms whereby Aβ is released remain elusive. We have earlier shown that Aβ can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular Aβ levels. Therefore, we considered whether Aβ could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of Aβ were found to be produced in pure synaptic vesicle preparations. We also studied the release of glutamate and Aβ from rat cortical nerve terminals (synaptosomes). We found that large amounts of Aβ were secreted from non-stimulated synaptosomes, from which glutamate was not released. On the contrary, we could not detect any differences in Aβ release between non-stimulated synaptosomes and synaptosomes stimulated with KCl or 4-aminopyridine, whereas glutamate release was readily inducible in this system. To conclude, our results indicate that the major release mechanism of Aβ from isolated nerve terminals differs from the synaptic release of glutamate and that the activity-dependent increase of secreted Aβ, reported by several groups using intact cells, is likely dependent on post-synaptic events, trafficking and/or protein synthesis mechanisms.
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| 27. |
- Lundgren, Jolanta L, et al.
(författare)
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ADAM10 and BACE1 are localized to synaptic vesicles.
- 2015
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 135:3, s. 606-615
-
Tidskriftsartikel (refereegranskat)abstract
- Synaptic degeneration and accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain are hallmarks of Alzheimer disease. Aβ is produced by sequential cleavage of its precursor protein, APP, by the β-secretase BACE1 and γ-secretase. However, Aβ generation is precluded if APP is cleaved by the α-secretase ADAM10 instead of BACE1. We have previously shown that Aβ can be produced locally at the synapse. To study the synaptic localization of the APP processing enzymes we used western blotting to demonstrate that, compared to total brain homogenate, ADAM10 and BACE1 were greatly enriched in synaptic vesicles isolated from rat brain using controlled-pore glass chromatography, whereas Presenilin1 was the only enriched component of the γ-secretase complex. Moreover, we detected ADAM10 activity in synaptic vesicles and enrichment of the intermediate APP-C-terminal fractions (APP-CTFs). We confirmed the western blotting findings using in situ proximity ligation assay to demonstrate close proximity of ADAM10 and BACE1 with the synaptic vesicle marker synaptophysin in intact mouse primary hippocampal neurons. In contrast, only sparse co-localization of active γ-secretase and synaptophysin was detected. These results indicate that the first step of APP processing occurs in synaptic vesicles whereas the final step is more likely to take place elsewhere. This article is protected by copyright. All rights reserved.
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| 28. |
- Martinsson, Isak, et al.
(författare)
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APP depletion alters selective pre- and post-synaptic proteins
- 2019
-
Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 95, s. 86-95
-
Tidskriftsartikel (refereegranskat)abstract
- The normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synaptic pruning during development. The effect of APP knockout on mature synapses is complicated by this role in development. We previously reported on differential changes in synaptic proteins and receptors in APP mutant AD transgenic compared to wild-type neurons, which revealed selective decreases in levels of pre- and post-synaptic proteins, including of surface glutamate receptors. In the present study, we undertook a similar analysis of synaptic composition but now in APP knockout compared to wild-type mouse neurons. Here we demonstrate alterations in levels of selective pre- and post-synaptic proteins and receptors in APP knockout compared to wild-type mouse primary neurons in culture and brains of mice in youth and adulthood. Remarkably, we demonstrate selective increases in levels of synaptic proteins, such as GluA1, in neurons with APP knockout and with RNAi knockdown, which tended to be opposite to the reductions seen in AD transgenic APP mutant compared to wild-type neurons. These data reinforce that APP is important for the normal composition of synapses.
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| 29. |
- Matt, C. E., et al.
(författare)
-
Direct observation of orbital hybridisation in a cuprate superconductor
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper-oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital (d(x2-y2) and d(z2)) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.
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| 30. |
- Matt, C. E., et al.
(författare)
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Electron scattering, charge order, and pseudogap physics in La1.6-xNd0.4SrxCuO4 : An angle-resolved photoemission spectroscopy study
- 2015
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 92:13
-
Tidskriftsartikel (refereegranskat)abstract
- We report an angle-resolved photoemission study of the charge stripe ordered La1.6-xNd0.4SrxCuO4 (Nd-LSCO) system. A comparative and quantitative line-shape analysis is presented as the system evolves from the overdoped regime into the charge ordered phase. On the overdoped side (x = 0.20), a normal-state antinodal spectral gap opens upon cooling below 80 K. In this process, spectral weight is preserved but redistributed to larger energies. A correlation between this spectral gap and electron scattering is found. A different line shape is observed in the antinodal region of charge ordered Nd-LSCO x = 1/8. Significant low-energy spectral weight appears to be lost. These observations are discussed in terms of spectral-weight redistribution and gapping originating from charge stripe ordering.
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| 31. |
- Månsson, Martin, et al.
(författare)
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Electronic structure and electron dynamics at the GaSb(001) surface studied by femtosecond pump-and-probe pulsed laser photoemission spectroscopy
- 2006
-
Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 252:15, s. 5308-5311
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Tidskriftsartikel (refereegranskat)abstract
- Transiently excited electron states at the GaSb(001) surface have been studied by means of time- and angle-resolved photoemission spectroscopy based on a femtosecond laser system. A normally unpopulated surface electron state has been found at similar to 250 meV above the valence band maximum with a strong confinement at the center of the surface Brillouin zone. The lifetime of transiently excited carriers at the intergap surface states has been found to be similar to 11 ps, associated with rapid carrier diffusion.
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| 32. |
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| 33. |
- Månsson, Martin, et al.
(författare)
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On-board sample cleaver
- 2007
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 78:7, s. 076103-
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Tidskriftsartikel (refereegranskat)abstract
- An on-board sample cleaver has been developed in order to cleave small and hard-to-cleave samples. To acquire good cleaves from rigid samples the alignment of the cleaving blade with respect to the internal crystallographic planes is crucial. To have the opportunity to mount the sample and align it to the blade ex situ has many advantages. The design presented has allowed us to cleave very tiny and rigid samples, e.g., the high-temperature superconductor La(2-x)SrxCuO4. Further, in this design the sample and the cleaver will have the same temperature, allowing us to cleave and keep the sample at low temperature. This is a big advantage over prior cleaver systems. As a result, better surfaces and alignments can be realized, which considerably simplifies and improves the experiments.
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| 34. |
- Månsson, Martin, et al.
(författare)
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Ultrafast electron dynamics and recombination at the Ge(111): Sn(root 3 X root 3)R30 degrees surface
- 2008
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Ingår i: Surface Science Letters. - : Elsevier BV. - 0039-6028. ; 602:5, s. L33-L37
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first study revealing the electronic structure and electron dynamics of the excited adatom state at the Ge(111): Sn(root 3 x root 3)R30 degrees surface. By the use of time- and angle-resolved photoemission spectroscopy, the normally unoccupied electronic structure of the partly empty Sn adatom can be probed. From the angle-resolved data we conclude that the adatom electrons at the Ge:Sn surface are more delocalized than at the clean Ge(111)c(2 x 8) surface. A unique pump-and-probe technique, based on a pulsed femtosecond laser-system, has also allowed us to study the recombination process of the excited state. We connect the recombination process of the excited electrons to the coherent fluctuations of the Sn adatoms. As a result we present an estimate for the time between each collective and coherent adatom flip Delta t = 9 ps, i.e. an adatom switching frequency nu(SW) approximate to 0.1 THz. We find that our results, contrary to scanning tunneling microscopy measurements [F. Ronci, S. Colonna, S.D. Thorpe, A. Cricenti, G. Le Lay, Phys. Rev. Lett. 95 (2005) 156101], agree very well with values extracted from molecular dynamics simulations found in the literature [J. Avila, A. Mascaraque, E.G. Michel, M.C. Asensio, G. Le Lay, J. Ortega, R. Perez, F. Flores, Phys. Rev. Lett. 82 (1999) 442; D. Farias, W. Kaminski, J. Lobo, J. Ortega, E. Hulpke, R. Perez, F. Flores, E.G. Michel, Phys. Rev. Lett. 91 (2003) 16103].
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| 35. |
- Nahalkova, Jarmila, et al.
(författare)
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CD147, a gamma-secretase associated protein is upregulated in Alzheimer's disease brain and its cellular trafficking is affected by presenilin-2
- 2010
-
Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 56:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase activity has been extensively investigated due to its role in Alzheimer's disease. Here, we studied the association of CD147, a transmembrane glycoprotein belonging to the immunoglobulin family, with gamma-secretase and its expression in Alzheimer's disease and control tissues. Subcellular fractionation of postmitochondrial supernatant from Fat brain on step iodixanol gradient in combination with co-immunoprecipitation using an anti-nicastrin antibody showed association of limited amount of CD147 to gamma-secretase. By immunoblotting of postnuclear pellets from Alzheimer's disease and control human brain tissues we showed that CD147 with molecular weight 75 kDa is upregulated in frontal cortex and thalamus of the Alzheimer's disease brains. Immunohistochemistry of brain tissues from Alzheimer's disease and control revealed specific Upregulation of CD147 in neurons, axons and capillaries of Alzheimer's disease frontal cortex and thalamus. The effect of presenilin-1 and -2, which are the catalytic subunits of gamma-secretase, on CD147 expression and subcellular localization was analyzed by confocal microscopy in combination with flow cytometry and showed that PS2 affected the subcellular localization of CD147 in Mouse embryonic fibroblast cells. We suggest that a small fraction of CD147 present in the brain is associated with the gamma-secretase, and can be involved in mechanisms dysregulated in Alzheimer's disease brain.
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| 36. |
- Nilsson, Per, et al.
(författare)
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Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice
- 2015
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 15:19, s. 3349-3355
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a neurodegenerative disease displaying extracellular plaques formed by the neurotoxic amyloid -peptide (A), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relate to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major A-degrading enzyme and a lack thereof increases A levels in the brain twofold. To identify altered protein expression levels induced by increased A levels, we performed a proteomic analysis of the brain of the AD mouse model APPsw and compared it to that of APPsw mice lacking neprilysin. To this end we established an LC-MS/MS method to analyze brain homogenate, using an O-18-labeled internal standard to accurately quantify the protein levels. To distinguish between alterations in protein levels caused by increased A levels and those induced by neprilysin deficiency independently of A, the brain proteome of neprilysin deficient APPsw mice was also compared to that of neprilysin deficient mice. By this approach we identified approximately 600 proteins and the levels of 300 of these were quantified. Pathway analysis showed that many of the proteins with altered expression were involved in neurological disorders, and that tau, presenilin and APP were key regulators in the identified networks. The data have been deposited to the ProteomeXchange Consortium with identifiers PXD000968 and PXD001786 ( and (). Interestingly, the levels of several proteins, including some not previously reported to be linked to AD, were associated with increased A levels.
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| 37. |
- Palmgren, Pål, et al.
(författare)
-
Chemical reaction and interface formation on InAs(111)-Co surfaces
- 2005
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Ingår i: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 574:2-3, s. 181-192
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Tidskriftsartikel (refereegranskat)abstract
- We report a study of the initial interface formation of Co on InAs(1 1 1)A and B surfaces using high resolution photoelectron spectroscopy and scanning tunneling microscopy. We observe a strong chemical interaction between Co and, in particular, surface indium forming a metallic overlayer already below monolayer coverage. On annealed surfaces this overlayer agglomerates into islands, with a narrow size distribution. Furthermore, no two-dimensional electron gas is formed on InAs(1 1 1)A-Co in contrast to the clean surface.
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| 38. |
- Philipson, Ola, et al.
(författare)
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The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ
- 2012
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:5, s. 1010.e1-1010.e13
-
Tidskriftsartikel (refereegranskat)abstract
- The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.
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| 39. |
- Razzoli, E., et al.
(författare)
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The Fermi surface and band folding in La2-xSrxCuO4, probed by angle-resolved photoemission
- 2010
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 12, s. 125003-
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Tidskriftsartikel (refereegranskat)abstract
- A systematic angle-resolved photoemission study of the electronic structure of La2-xSrxCuO4 in a wide doping range is presented in this paper. In addition to the main energy band, we observed a weaker additional band, the (pi, pi) folded band, which shows unusual doping dependence. The appearance of the folded band suggests that a Fermi surface reconstruction is doping dependent and could already occur at zero magnetic field.
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| 40. |
- Sandebring, Anna, et al.
(författare)
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The Pathogenic A beta 43 Is Enriched in Familial and Sporadic Alzheimer Disease
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e55847-
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloid-cascade hypothesis posits that the role of amyloid beta-peptide (A beta) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of A beta are produced, of which the 40 and 42 residue variants (A beta 40 and A beta 42) are the most common. A beta 42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer A beta isoforms, like the less studied A beta 43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate A beta 43 in AD, we conducted a quantitative study on A beta 43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of A beta 43, as well as A beta 40 and A beta 42, were quantified using ELISA. We compared quantitative data showing A beta levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed A beta 43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. A beta 42 and A beta 43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of A beta 43 in human brain are low compared to A beta 40 and A beta 42, we suggest that A beta 43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.
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| 41. |
- Sassa, Y., et al.
(författare)
-
Probing two- and three-dimensional electrons in MgB2 with soft x-ray angle-resolved photoemission
- 2015
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 91:4, s. 045114-
-
Tidskriftsartikel (refereegranskat)abstract
- electronic band structure of MgB2 involves a unique combination of two-and three-dimensional (3D) electrons derived from the boron sigma and pi states, respectively. We have mapped out the sigma and pi bands over the complete Brillouin zone, including the full disconnected Fermi surface, using high-resolution soft x-ray angle-resolved photoelectron spectroscopy. The measured band structure, which is closely related to that of graphene, is in overall good agreement with the density functional theory-general gradient approximation (DFT-GGA), though differences in Fermi surface volume are seen. Surprisingly, the measured bands are wider than calculated, by similar to 8% for the s and similar to 10-15% for the p bands. This solves the long-standing challenge of establishing the full 3D electronic structure of the model compound MgB2, and it demonstrates the tendency of DFT-GGA to overestimate the band narrowing due to exchange correlations effects.
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| 42. |
- Sassa, Yasmine, et al.
(författare)
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The metallic quasi-1D spin-density-wave compound NaV2O4 studied by angle-resolved photoelectron spectroscopy
- 2018
-
Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : ELSEVIER SCIENCE BV. - 0368-2048 .- 1873-2526. ; 224, s. 79-83
-
Tidskriftsartikel (refereegranskat)abstract
- Angle-resolved photoelectron spectroscopy has been used to follow the valence band and near Fermi edge electronic band structure in the quasi-1D compound NaV2O4. In this current study we have acquired the very first high-quality, high-resolution ARPES data from this material. Our data clearly reveal two distinct dispersive bands that cross the Fermi level at different k(F). This is a clear signature that the electronic properties of this material is affected by the presence of a mixed valence state on the different vanadium chains and possibly also the low-temperature magnetic spin order.
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| 43. |
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| 44. |
- Schedin-Weiss, Sophia, et al.
(författare)
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Super-resolution microscopy reveals gamma-secretase at both sides of the neuronal synapse
- 2016
-
Ingår i: Acta neuropathologica communications. - : BioMed Central. - 2051-5960. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- The transmembrane protein assembly gamma-secretase is a key protease in regulated intramembrane processing (RIP) of around 100 type-1 transmembrane proteins. Importantly, it has a pathological role in Alzheimer disease (AD) as it generates the neurotoxic amyloid beta-peptide from the amyloid precursor protein (APP). Studies on gamma-secretase location are therefore crucial both from a biological and a therapeutic perspective. Despite several years of efforts in many laboratories, it is not clear where in the neuron gamma-secretase exerts it's activities. Technical challenges include the fact that the active enzyme contains four protein components and that most subcellular compartments cannot be spatially resolved by traditional light microscopy. Here, we have used a powerful combination of the two nanoscopy techniques STORM and STED microscopy to visualize the location of gamma-secretase in neurons using an active-site specific probe, with a focus on the synapse. We show that gamma-secretase is present in both the pre-and postsynaptic compartments. We further show that the enzyme is enriched very close to the synaptic cleft in the postsynaptic membrane, as well as to NMDA receptors, demonstrating that gamma-secretase is present in the postsynaptic plasma membrane. Importantly, the expression of gamma-secretase increased in the pre-and postsynaptic compartments with the size of the synapse, suggesting a correlation between gamma-secretase activity and synapse maturation. Thus, our data shows the synaptic location with high precision in three dimensions and settles the long-lasting debate on the synaptic location of gamma-secretase.
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| 45. |
- Szamota Leandersson, Karolina, et al.
(författare)
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Interaction between oxygen and InAs(111) surfaces, influence of the electron accumulation layer
- 2003
-
Ingår i: Applied Surface Science. - 0169-4332 .- 1873-5584. ; 212, s. 589-594
-
Tidskriftsartikel (refereegranskat)abstract
- The oxidation of InAs(1 1 1) surfaces has been studied by photoelectron spectroscopy. Both the InAs(1 1 1)A and the InAs(1 1 1)B surfaces are studied and it. is found that the initial oxidation follows different paths for the two surfaces. At low oxygen exposures of the A face the Fermi level structure, which is due to the electron accumulation layer, increases in intensity. On the B-side the intensity of the lone pair surface state decreases with increasing oxygen exposure. For larger exposures significant changes can be observed in the line shape of the In 4d and the As 3d core levels.
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| 46. |
- Teranishi, Yasuhiro, et al.
(författare)
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Erlin-2 is associated with active γ-secretase in brain and affects amyloid β-peptide production
- 2012
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 424:3, s. 476-481
-
Tidskriftsartikel (refereegranskat)abstract
- The transmembrane protease complex γ-secretase is responsible for the generation of the neurotoxic amyloid β-peptide (Aβ) from its precursor (APP). Aβ has a causative role in Alzheimer disease, and thus, γ-secretase is a therapeutic target. However, since there are more than 70 γ-secretase substrates besides APP, selective inhibition of APP processing is required. Recent data indicates the existence of several γ-secretase associated proteins (GSAPs) that affect the selection and processing of substrates. Here, we use a γ-secretase inhibitor for affinity purification of γ-secretase and associated proteins from microsomes and detergent resistant membranes (DRMs) prepared from rat or human brain. By tandem mass spectrometry we identified a novel brain GSAP; erlin-2. This protein was recently reported to reside in DRMs in the ER. A proximity ligation assay, as well as co-immunoprecipitation, confirmed the association of erlin-2 with γ-secretase. We found that a higher proportion of erlin-2 was associated with γ-secretase in DRMs than in soluble membranes. siRNA experiments indicated that reduced levels of erlin-2 resulted in a decreased Aβ production, whereas the effect on Notch processing was limited. In summary, we have found a novel brain GSAP, erlin-2, that resides in DRMs and affects Aβ production.
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| 47. |
- Tjernberg, L O, et al.
(författare)
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Amyloid beta-peptide polymerization studied using fluorescence correlation spectroscopy
- 1999
-
Ingår i: Chemistry and Biology. - 1074-5521 .- 1879-1301. ; 6:1, s. 53-62
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The accumulation of fibrillar deposits of amyloid beta-peptide (A beta) in brain parenchyma and cerebromeningeal blood vessels is a key step in the pathogenesis of Alzheimer's disease. In this report, polymerization of A beta was studied using fluorescence correlation spectroscopy (FCS), a technique capable of detecting small molecules and large aggregates simultaneously in solution. Results: The polymerization of A beta dissolved in Tris-buffered saline, pH 7.4, occurred above a critical concentration of 50 mu M and proceeded from monomers/dimers into two discrete populations of large aggregates, without any detectable amount of oligomers. The aggregation showed very high cooperativity and reached a maximum after 40 min, followed by an increase in the amount of monomers/dimers and a decrease in the size of the large aggregates. Electron micrographs of samples prepared at the time for maximum aggregation showed a mixture of an amorphous network and short diffuse fibrils, whereas only mature amyloid fibrils were detected after one day of incubation. The aggregation was reduced when A beta was incubated in the presence of A beta ligands, oligopeptides previously shown to inhibit fibril formation, and aggregates were partly dissociated after the addition of the ligands. Conclusions: The polymerization of A beta is a highly cooperative process in which the formation of very large aggregates precedes the formation of fibrils. The entire process can be inhibited and, at least in early stages, partly reversed by A beta ligands.
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| 48. |
- Tjernberg, L. O., et al.
(författare)
-
Transmissible amyloid
- 2016
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:2, s. 153-163
-
Forskningsöversikt (refereegranskat)abstract
- There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. Read more articles from the symposium: Amyloid - a multifaceted player in human health and disease.
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| 49. |
- Tjernberg, O, et al.
(författare)
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Evidence of pseudogap related core level shifts in Bi2Sr2Ca1-xYxCu2O8+delta
- 1997
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Ingår i: PHYSICAL REVIEW LETTERS. - : AMER INST PHYSICS. - 0031-9007. ; 79:3, s. 499-502
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Photoelectron spectroscopy data from Bi2Sr2Ca1-xYxCu2O8+delta Single crystals, for x = 0, 0.16, and 0.55, are presented. It is shown that there are core level shifts related to the opening of a pseudogap and that similar shifts are observed at the opening
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| 50. |
- Wanngren, Johanna, et al.
(författare)
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Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations.
- 2014
-
Ingår i: FEBS Open Bio. - : Wiley. - 2211-5463. ; 4, s. 393-406
-
Tidskriftsartikel (refereegranskat)abstract
- The enzyme complex γ-secretase generates amyloid β-peptide (Aβ), a 37-43-residue peptide associated with Alzheimer disease (AD). Mutations in presenilin 1 (PS1), the catalytical subunit of γ-secretase, result in familial AD (FAD). A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio), but the molecular mechanisms responsible remain elusive. In this report we have studied the impact of several different PS1 FAD mutations on the integration of selected PS1 transmembrane domains and on PS1 active site conformation, and whether any effects translate to a particular amyloid precursor protein (APP) processing phenotype. Most mutations studied caused an increase in the Aβ42/Aβ40 ratio, but via different mechanisms. The mutations that caused a particular large increase in the Aβ42/Aβ40 ratio did also display an impaired APP intracellular domain (AICD) formation and a lower total Aβ production. Interestingly, seven mutations close to the catalytic site caused a severely impaired integration of proximal transmembrane/hydrophobic sequences into the membrane. This structural defect did not correlate to a particular APP processing phenotype. Six selected FAD mutations, all of which exhibited different APP processing profiles and impact on PS1 transmembrane domain integration, were found to display an altered active site conformation. Combined, our data suggest that FAD mutations affect the PS1 structure and active site differently, resulting in several complex APP processing phenotypes, where the most aggressive mutations in terms of increased Aβ42/Aβ40 ratio are associated with a decrease in total γ-secretase activity.
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