| 1. |
- Bergemalm, Daniel, et al.
(författare)
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Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model mice
- 2010
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 114:2, s. 408-418
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Tidskriftsartikel (refereegranskat)abstract
- Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from four different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intra-subunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, four were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.
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| 2. |
- Robroek, Bjorn J. M., et al.
(författare)
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Microclimatological consequences for plant and microbial composition in Sphagnum-dominated peatlands
- 2014
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Ingår i: Boreal environment research. - Helsinki, Finland : Finnish Environment Institute. - 1239-6095 .- 1797-2469. ; 19:3, s. 195-208
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Tidskriftsartikel (refereegranskat)abstract
- In three Scandinavian peatlands we studied to what extent plant and microbial community compositions are governed by local-scale microhabitat, with a special interest in the effect of aspect (i.e. exposition of slopes). Despite differences in solar irradiance between the south- and north-facing slopes, maximum temperature was elevated in the south-facing slopes at the most northern site only. Pore-water nutrient concentrations were not affected by aspect, yet dissolved organic carbon concentrations were higher in the south-facing microhabitats. This was likely caused by higher vascular plant biomass. Plant and microbial community composition clearly differed among sites. In all three sites, microhabitat (i.e. prevailing water-table depth) affected the plant and microbial community compositions. Aspect, however, did not affect community composition, even though microclimate significantly differed between the south- and the north-facing aspects at the northernmost site. Our results highlight the complex link between plant community composition, microbial community and environmental conditions, which deserves much more attention than currently in order to fully understand the effects of climate change on peatland ecosystem function.
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| 3. |
- Wuolikainen, Anna, 1980-, et al.
(författare)
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ALS patients with mutations in the SOD1 gene have an unique metabolomic profile in the cerebrospinal fluid compared with ALS patients without mutations
- 2012
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier. - 1096-7192 .- 1096-7206. ; 105:3, s. 472-478
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Tidskriftsartikel (refereegranskat)abstract
- A specific biochemical marker for early diagnosing and for monitoring disease progression in amyotrophic lateral sclerosis (ALS) will have important clinical applications. ALS is a heterogeneous syndrome with multiple subtypes with ill-defined borders. A minority of patients carries mutations in the Cu/Zn-superoxide dismutase (SOD1) gene but the disease mechanism remains unknown for all types of ALS. Using a GC-TOFMS platform we studied the cerebrospinal fluid (CSF) metabolome in 16 ALS patients with six different mutations in the SOD1 gene and compared with ALS-patients without such mutations. OPLS-DA was used for classification modeling. We find that patients with a SOD1 mutation have a distinct metabolic profile in the CSF. In particular, the eight patients homozygous for the D90A SOD1 mutation showed a distinctively different signature when modeled against ALS patients with other SOD1 mutations and sporadic and familial ALS patients without a SOD1 gene mutation. This was found irrespective of medication with riluzole and survival time. Among the metabolites that contributed most to the CSF signature were arginine, lysine, ornithine, serine, threonine and pyroglutamic acid, all found to be reduced in patients carrying a D90A SOD1 mutation. ALS-patients with a SOD1 gene mutation appear as a distinct metabolic entity in the CSF, in particular in patients with the D90A mutation, the most frequently identified cause of ALS. The findings suggest that metabolomic profiling using GC-TOFMS and multivariate data analysis may be a future tool for diagnosing and monitoring disease progression, and may cast light on the disease mechanisms in ALS.
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