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- Madani, Fatemeh, et al.
(författare)
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Perturbations of model membranes induced by pathogenic dynorphin A mutants causing neurodegeneration in human brain
- 2011
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 411:1, s. 111-114
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Tidskriftsartikel (refereegranskat)abstract
- Several effects of the endogenous opioid peptide dynorphin A (Dyn A) are not mediated through the opioid receptors. These effects are generally excitatory, and result in cell loss and induction of chronic pain and paralysis. The mechanism(s) is not well defined but may involve formation of pores in cellular membranes. In the 17-amino acid peptide Dyn A we have recently identified L5S, R6W, and R9C mutations that cause the dominantly inherited neurodegenerative disorder Spinocerebellar ataxia type 23. To gain further insight into non-opioid neurodegenerative mechanism(s), we studied the perturbation effects on lipid bilayers of wild type Dyn A and its mutants in large unilamellar phospholipid vesicles encapsulating the fluorescent dye calcein. The peptides were found to induce calcein leakage from uncharged and negatively charged vesicles to different degrees, thus reflecting different membrane perturbation effects. The mutant Dyn A R6W was the most potent in producing leakage with negatively charged vesicles whereas Dyn A L5S was virtually inactive. The overall correlation between membrane perturbation and neurotoxic response [3] suggests that pathogenic Dyn A actions may be mediated through transient pore formation in lipid domains of the plasma membrane.
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| 4. |
- Lindgren, Joel, et al.
(författare)
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N-terminal engineering of amyloid-beta-binding Affibody molecules yields improved chemical synthesis and higher binding affinity
- 2010
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
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| 7. |
- Shearer, Brian M, et al.
(författare)
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Sexual dimorphism in human browridge volume measured from 3D models of dry crania: A new digital morphometrics approach
- 2012
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 222:1-3
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Tidskriftsartikel (refereegranskat)abstract
- Sex estimation from the human skull is often a necessary step when constructing a biological profile from unidentified human remains. Traditional methods for determining the sex of a skull require observers to rank the expression of sexually dimorphic skeletal traits by subjectively assessing their qualitative differences. One of these traits is the prominence of the glabellar region above the browridge. In this paper, the volume of the browridge region was measured from digital 3D models of 128 dry crania ( 65 female, 63 male). The 3D models were created with a desktop laser scanner, and the browridge region of each 3D model was isolated using geometric planes defined by cranial landmarks. Statistical analysis of browridge-to-cranium volume ratios revealed significant differences between male and female crania. Differences were also observed between geographically distinct populations, and between temporally distinct populations from the same locale. The results suggest that in the future, sex determination of human crania may be assisted by quantitative computer-based volume calculations from 3D models, which can provide increased objectivity and repeatability when compared to traditional forensic techniques. The method presented in this paper can easily be extended to other volumetric regions of the human cranium.
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| 8. |
- Warmlander, Sebastian K. T. S., et al.
(författare)
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Amulets rather than iron bars. Metallographic analysis indicates uneven material quality in Vendel Period iron rings from Aselby in Stora Tuna parish, Dalecarlia
- 2018
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Ingår i: Fornvännen. - : Royal Academy Letters, History & Antiquities. - 0015-7813 .- 1404-9430. ; 113:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- 29 iron rings with diameters between 9 and 15 cm were excavated in 1989 at a Vendel Period settlement site with a longhouse, located at Aselby in Dalecarlia, Sweden. Most of the rings had between one and three smaller rings attached. Rings of this type and size are fairly common at Scandinavian Vendel and Viking Period sites - settlements, cemeteries and cult precincts - but their function remains debated. The rings from Aselby have been interpreted as iron/steel bars, to be used or traded as raw material for e.g. weapons production. Previous metallurgical analysis of one Aselby ring showed it to consist of somewhat uneven but still decent-quality carbon steel. General conclusions should however not be drawn from a single observation. Here, we have sampled six Aselby rings for metallographic examination of the cross-sections. The material quality and carbon content of the sampled rings were found to be very uneven, and relatively large inclusions of unworked slag were common. We conclude that the rings were not bars of raw material. Instead, they may have been amulet rings, intended for ritual use. If so, our results suggest that the material properties of amulet rings may have been less important during rituals it may have sufficed that the rings had the right shape.
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