| 1. |
- Conrad, Chris, et al.
(författare)
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Single molecule profiling of tau gene expression in Alzheimer's disease
- 2007
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:3, s. 1228-1236
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Tidskriftsartikel (refereegranskat)abstract
- Tau is a microtubule-associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer's disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single-molecule-based technology, polymerase colony or polony, to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2-beta-1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging-related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing-based therapeutics is an emerging area of drug development, and a well-defined and quantitative assay for monitoring single-gene transcriptome will be relevant for such development.
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| 2. |
- Hollaender, H. M., et al.
(författare)
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Comparative predictions of discharge from an artificial catchment (Chicken Creek) using sparse data
- 2009
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 13:11, s. 2069-2094
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Tidskriftsartikel (refereegranskat)abstract
- Ten conceptually different models in predicting discharge from the artificial Chicken Creek catchment in North-East Germany were used for this study. Soil texture and topography data were given to the modellers, but discharge data was withheld. We compare the predictions with the measurements from the 6 ha catchment and discuss the conceptualization and parameterization of the models. The predictions vary in a wide range, e.g. with the predicted actual evapotranspiration ranging from 88 to 579 mm/y and the discharge from 19 to 346 mm/y. The predicted components of the hydrological cycle deviated systematically from the observations, which were not known to the modellers. Discharge was mainly predicted as subsurface discharge with little direct runoff. In reality, surface runoff was a major flow component despite the fairly coarse soil texture. The actual evapotranspiration (AET) and the ratio between actual and potential ET was systematically overestimated by nine of the ten models. None of the model simulations came even close to the observed water balance for the entire 3-year study period. The comparison indicates that the personal judgement of the modellers was a major source of the differences between the model results. The most important parameters to be presumed were the soil parameters and the initial soil-water content while plant parameterization had, in this particular case of sparse vegetation, only a minor influence on the results.
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| 3. |
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| 4. |
- Stamm, T, et al.
(författare)
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I have mastered the challenge of living with a chronic disease: life stories of people with rheumatoid arthritis
- 2008
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Ingår i: Qualitative health research. - : SAGE Publications. - 1049-7323 .- 1552-7557. ; 18:5, s. 658-669
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Tidskriftsartikel (refereegranskat)abstract
- Our aim with this study was to explore the narrative life story of individuals diagnosed with rheumatoid arthritis. An open qualitative approach, namely narrative biographic methodology, was applied to include the life context of the participants and to deliberately exclude predefinitions of concepts. Ten people with rheumatoid arthritis who retired early because of the disease participated and were interviewed three times according to a narrative biographic interview style. The biographical data and the interview texts were analyzed both individually and in comparison to each other. Some participants regarded rheumatoid arthritis as a challenge for mastery in their lives, whereas others adapted to the disease and “made the best out of a bad situation.” Especially in countries where the medical model predominates in health care, our findings can be used to broaden the current view that some health professionals have toward patients, and stress the importance of patients being self-responsible.
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