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- Ahrens, J., et al.
(author)
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Results from AMANDA
- 2001
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In: Proceedings, 9th International Workshop, Venice, Italy, March 6-9, 2001. Vol. 1, 2. ; , s. 569-580
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Conference paper (peer-reviewed)
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| 6. |
- Kirik, Deniz, et al.
(author)
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Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system
- 2002
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In: The Journal of Neuroscience. - 1529-2401. ; 22:7, s. 2780-2791
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Journal article (peer-reviewed)abstract
- Recombinant adeno-associated viral vectors display efficient tropism for transduction of the dopamine neurons of the substantia nigra. Taking advantage of this unique property of recombinant adeno-associated viral vectors, we expressed wildtype and A53T mutated human alpha-synuclein in the nigrostriatal dopamine neurons of adult rats for up to 6 months. Cellular and axonal pathology, including alpha-synuclein-positive cytoplasmic inclusions and swollen, dystrophic neurites similar to those seen in brains from patients with Parkinson's disease, developed progressively over time. These pathological alterations occurred preferentially in the nigral dopamine neurons and were not observed in other nondopaminergic neurons transduced by the same vectors. The degenerative changes were accompanied by a loss of 30-80% of the nigral dopamine neurons, a 40-50% reduction of striatal dopamine, and tyrosine hydroxylase levels that was fully developed by 8 weeks. Significant motor impairment developed in those animals in which dopamine neuron cell loss exceeded a critical threshold of 50-60%. At 6 months, signs of cell body and axonal pathology had subsided, suggesting that the surviving neurons had recovered from the initial insult, despite the fact that alpha-synuclein expression was maintained at a high level. These results show that nigral dopamine neurons are selectively vulnerable to high levels of either wild-type or mutant alpha-synuclein, pointing to a key role for alpha-synuclein in the pathogenesis of Parkinson's disease. Targeted overexpression of alpha-synuclein in the nigrostriatal system may provide a new animal model of Parkinson's disease that reproduces some of the cardinal pathological, neurochemical, and behavioral features of the human disease.
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| 8. |
- Rosenqvist, Nina, et al.
(author)
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Activation of silenced transgene expression in neural precursor cell lines by inhibitors of histone deacetytation
- 2002
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In: Journal of Gene Medicine. - : Wiley. - 1521-2254 .- 1099-498X. ; 4:3, s. 248-257
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Journal article (peer-reviewed)abstract
- Background Ex vivo gene therapy in the central nervous system (CNS) holds great promise for diseases such as the neurodegenerative disorders. However, achieving stable, long-term transgene expression in grafted cells has proven problematic. This study reports the establishment of an in vitro model of transgene down-regulation in cells grafted to the CNS using the immortalized neural progenitor cell lines HiB5 and RN33B. Methods Neural cell lines were transduced at 33 C with different GFP constructs, both viral and non-viral, containing either viral or non-viral promoters. Cell differentiation in vitro was obtained by culturing the cells at 37 C in serum-free defined media, which halts cell division, and GFP-expression was analysed by FACS. As early as day 3 of culture at 37degreesC, the transgene expression decreased markedly in most cell lines. To validate the assay, the same clones were grafted to the adult rat striatum and the down-regulation of GFP-expression was evaluated. Results The temporal pattern of down-regulation was found to be similar in vitro and in vivo. Using this assay, it was shown that addition of inhibitors of histone deacetylation, but not an inhibitor of DNA methylation, reversed the silencing of GFP in quiescent neural progenitors by up to 308% of control values. Conclusion These results suggest that the same mechanisms controlling gene transcription of the host cell's genome are active in controlling transgene expression and that this should be taken into account when constructing vectors for gene therapy. The assay reported in this study could be used as a screening method to evaluate new vectors. Copyright (C) 2002 John Wiley Sons, Ltd.
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| 9. |
- Åkesson, Torsten, et al.
(author)
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Aging studies for the ATLAS Transition Radiation Tracker (TRT)
- 2003
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In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 515:1-2, s. 166-179
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Conference paper (peer-reviewed)abstract
- A summary of the aging and material validation studies carried out for the ATLAS Transition Radiation Tracker (TRT) is presented. Particular emphasis is put on the different phenomena observed in straw tubes operating with the chosen Xe/CF4/CO2 mixture. The most serious effects observed are silicon deposition on the anode wire and damage of the anode wire gold plating. Etching phenomena and active radical effects are also discussed. With a careful choice of all materials and components, and with good control of the water contamination in the active gas, the ATLAS TRT will operate reliably for 10 years at the LHC design luminosity. To demonstrate this fully, more work is still needed on the gas system purification elements, in particular to understand their interplay with the active species containing fluorine created in the avalanche process under irradiation.
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| 10. |
- Åkesson, Torsten, et al.
(author)
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An X-ray scanner for wire chambers
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 507:3, s. 622-635
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Journal article (peer-reviewed)abstract
- The techniques to measure the position of sense wires and field wires, the gas gain and the gas flow rate inside wire chambers using a collimated and filtered X-ray beam are reported. Specific examples are given using barrel modules of the Transition Radiation Tracker of the ATLAS experiment. (C) 2003 Elsevier B.V. All rights reserved.
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