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- Abelein, Axel, et al.
(författare)
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Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:32, s. 23518-23528
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Tidskriftsartikel (refereegranskat)abstract
- Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.
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| 6. |
- Isaxon, Christina, et al.
(författare)
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A Novel System for Source Characterization and Controlled Human Exposure to Nanoparticle Aggregates Generated During Gas–Metal Arc Welding
- 2013
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 47:1, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in Undetermined The aim of this study was to achieve a method to perform detailed characterization and human exposure studies of nanosized and nanostructured aerosol particles. The source chosen was mild steel, active gas, arc welding fume. The setup consisted of a generation chamber, where welding can be performed, connected to an airtight stainless steel 22 m(3) exposure chamber. Instrumentation, consisting of a tapered element oscillating microbalance, a scanning mobility particle sizer, and a sampler for electron microscopy and particle-induced X-ray emission analysis was connected to the stainless steel chamber. The feasibility of the system for human exposure studies was evaluated by exposing 31 human volunteers, in groups of three, to a test aerosol containing 1 mg/m(3) welding fumes and to conditioned, filtered air. The results show that an aerosol that accurately represents dilute welding fume exposures that occur in workplaces can be produced in a controlled manner, and that the experimental setup can be used for 6 h, double-blind, exposures of human subjects. Particle mass concentration levels could be varied from <5 mu g/m(3) to more than 1000 mu g/m(3). Fumes from metal active gas welding showed a unimodal size distribution with a mean mobility diameter of 160 nm, transmission electron microscopy showed aggregates with a clearly nanosized structure.
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| 7. |
- Isaxon, Christina, et al.
(författare)
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Realistic indoor nano-aerosols for a human exposure facility
- 2013
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 60, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to achieve realistic levels of two different types of aerosols commonly abundant in indoor environments in an experimental chamber intended for human exposure studies and aerosol characterization. The aerosols chosen were particles from candle lights (in particle number dominated by inorganic water soluble particles) and from ozone-terpene reactions (organic particles). The aerosol generation and characterization system consisted of a controlled air tight stainless steel 22 m(3) chamber, to which the generation set-ups were connected. No air could enter or leave the chamber except through a conditioning system by which temperature, relative humidity and air exchange rate could be controlled. Candle smoke aerosol was generated from ten candles burning in a 1.33 m(3) glass and stainless steel chamber. The aerosol was diluted by clean air from the conditioning system before entering the chamber. Terpene vapor was generated by passing pure nitrogen through a glass bottle containing limonene oil. Ozone was generated by a spark discharge using pure O-2, and was added to the ventilation air flow downstream the inlet for terpene vapors and upstream the inlet to the chamber. Both aerosols were characterized with respect to number and mass concentrations, size distribution and chemical composition. Particle number concentration in the size range 10-650 nm could be varied from <10 cm(-3) to more than 900,000 cm(-3) (for candle smoke) or to more than 30,000 cm(-3) (for particles formed in a 160 ppb terpene/40 ppb ozone mixture). Furthermore, the set-ups were evaluated by, for each source, repeating the generation at six three-hour long events. For both aerosols repeatable generations at pre-determined concentration levels, that were stable over time, could be achieved. The results show that realistic concentrations of aerosols from real-world environments could be reproduced in a well-controlled manner and that this set-up could be used both for aerosol characterization and for human exposures. (C) 2013 Elsevier Ltd. All rights reserved.
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- Jönsson, Lena S, et al.
(författare)
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Gene expression analysis in induced sputum from welders with and without airway-related symptoms.
- 2011
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; Okt, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To identify changes in gene expression in the airways among welders, with and without lower airway symptoms, working in black steel. METHODS: Included were 25 male, non-smoking welders. Each welder was sampled twice; before exposure (after vacation), and after 1 month of exposure. From the welders (14 symptomatic, of whom 7 had asthma-like symptoms), RNA from induced sputum was obtained for gene expression analysis. Messenger RNA from a subset of the samples (n = 7) was analysed with microarray technology to identify genes of interest. These genes were further analysed using quantitative PCR (qPCR; n = 22). RESULTS: By comparing samples before and after exposure, the microarray analysis resulted in several functional annotation clusters: the one with the highest enrichment score contained "response to wounding", "inflammatory response" and "defence response". Seven genes were analysed by qPCR: granulocyte colony-stimulating factor 3 receptor (CSF3R), superoxide dismutase 2, interleukin 8, glutathione S-transferase pi 1, tumour necrosis factor alpha-induced protein 6 (TNFAIP6), interleukin 1 receptor type II and matrix metallopeptidase 25 (MMP25). Increased levels of CSF3R, TNFAIP6 and MMP25 were indicated among asthmatic subjects compared to non-symptomatic subjects, although the differences did not reach significance. CONCLUSIONS: Workers' exposure to welding fumes changed gene expression in the lower airways in genes involved in inflammatory and defence response. Thus, microarray and qPCR technique can demonstrate markers of exposure to welding fumes and possible disease-related markers. However, further studies are needed to verify genes involved and to further characterise the mechanism for welding fumes-associated lower airway symptoms.
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