| 12611. |
- Kesek, Milos
(författare)
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Kammararytmier och AV-block
- 2010. - 4:e
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Ingår i: Akut kranskärlssjukdom. - : Liber. - 9789147093885 ; , s. 198-207
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12612. |
- Keskin, Isil, 1987-, et al.
(författare)
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Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in erythrocytes in ALS patients and their relatives
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Our objective was to in blood samples from 3723 individuals including ALS patients without a coding SOD1 mutation and 372 control individuals characterize stabilities of mutant SOD1s, compare SOD1 enzymatic activities between patients with different genetic causes of ALS, and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Erythrocyte SOD1 enzymatic activities normalized to hemoglobin content were determined. Coding SOD1 sequences were analyzed by Sanger sequencing, copy number variations by fragment length analysis and by TaqMan Assay. Hemoglobin disorders were searched for. Of the 46 SOD1 mutations found, ¾ caused severe destabilization of the mutant protein but in ¼ SOD1 was essentially physically stable. Mutations producing structural changes all caused halved SOD activities. There were no differences in SOD1 activities between controls and patients without any detected SOD1 mutations or patients with C9ORF72HRE or TBK1 mutations. In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Also, no uncommon variants in exon-flanking sequences were detected. Thalassemias and iron deficiency anemia were associated with increased SOD1 activity/hemoglobin ratios. In conclusion, adjunct erythrocyte SOD activity analysis is of value to signal the presence of exon and splice-site-intron mutations that influence the SOD1 structure.
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| 12613. |
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| 12614. |
- Keskin, Isil, 1987-
(författare)
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SOD, ORF and ALS: On the role of SOD1 and C9ORF72 in the pathogenesis of ALS
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyotrophic lateral sclerosis (ALS) is characterized by adult-onset degeneration of upper and lower motor neurons. Symptoms begin focally in one muscle and then spread contiguously, resulting in progressive paralysis and death from respiratory failure. Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause, however, mutations in SOD1 were the first identified and are found in 1-9% of patients. Misfolded SOD1 aggregates in the CNS are hallmarks of ALS associated with SOD1 mutations. However, accumulation of misfolded or aggregated SOD1 protein has also been reported in sporadic and familial ALS without SOD1 mutations, suggesting that wild-type SOD1 could play a role in ALS pathology in general.The aims of this thesis are: 1) To describe the resulting disease phenotype and specific characteristics of the SOD1 protein carrying the stable disease- associated mutation L117V. 2) To set up cell-based in vitro models to study the mechanisms of SOD1 misfolding and aggregation under physiologically relevant expression levels. 3) To compare SOD1 activity in patient-derived samples and screen for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.1) We identified a novel L117V SOD1 mutant in two families of Syrian origin that co-segregated with the disease. This mutation was associated with slow disease progression, reduced penetrance and a uniform phenotype. The L117V mutant protein was indistinguishable from wild-type SOD1 in terms of stability, dismutation activity and misfolding in patient-derived cell lines.2) We established patient-derived fibroblast and iPSC-MN lines expressing mutant SOD1 at physiological levels as in vitro models to study misfolding and aggregation of SOD1. We investigated the effects of several cellular pathway disturbances on SOD1 misfolding. Misfolded SOD1 was increased by inhibition of the ubiquitin-proteasome pathway in fibroblasts derived from both patients and controls. An age-related decline in proteasome activity could contribute to the late onset of ALS.Next, we studied the effects of low oxygen tension on misfolding and aggregation of SOD1 in patient-derived cells. Low O2 tensions were found to markedly increase C57-C146 disulphide reduction, misfolding and aggregation of SOD1. Importantly, the largest effects were detected in iPSC-MNs. This suggests that motor neurons are specifically vulnerable to misfolding and aggregation of SOD1 under low O2 tension.3) We compared the enzymatic activity of SOD1 in blood samples from a large number of ALS patients and controls. We screened for potential underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. No aberrations in copy number, other large structural changes in introns and exons or intronic mutations in the 30-50 bp flanking the exons were found in the 142 outliers, with either very low or very high SOD1 dismutation activities. However, hemoglobinopathies, including thalassemias and iron deficiency anemia, were associated with high SOD1/mg Hb ratios. Erythrocytes from patients with destabilizing SOD1 mutations showed half the normal activity. There were no significant differences in SOD1 activity between control individuals and ALS patients without a coding SOD1 mutation, or carriers of TBK1 mutations or the hexanucleotide repeat expansion in C9ORF72. Our result suggests that SOD1 enzymatic activity is not associated with the disease in non-SOD1 mutation ALS.
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| 12615. |
- Keskitalo, E. Carina H., 1974-
(författare)
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Adapting to climate change in Sweden : national policy development and adaptation measures in Västra Götaland
- 2010
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Ingår i: Developing Adaptation Policy and Pracitce in Europe. - Dordrecht : Springer Netherlands. - 9789048193240 - 9789048193257 ; , s. 189-232
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Located in south-western Sweden, the Vastra Gotaland region is often seen as one of the areas of the country most vulnerable to flooding and erosion, and will be highly impacted by flooding and sea level rise as a result of climate change Drawing upon a literature study and semi-structured interviews with actors in climate policy, this chapter reviews the development of adaptation policy in Sweden The chapter focuses particularly on the Commission on Climate and Vulnerability (2007) and a government bill An Integrated Climate and Energy Policy Climate (2009) in which suggestions by the Commission were included The chapter describes the development of adaptation policy and measures on the regional and local levels in Vastra Gotaland and within select municipalities The study illustrates the national distribution of responsibility through which municipalities are given a large role in integrating adaptation measures, and describes some of the differentiated responses such responsibilities may elicit on the local level.
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| 12616. |
- Keskitalo, E. Carina H., 1974-
(författare)
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Adaptive capacity and adaptation in Swedish multi-use boreal forests : sites of interaction between different land uses
- 2010
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Ingår i: Adaptive capacity and environmental governance. - Heidelberg : Springer. - 9783642121937 - 9783642121944 ; , s. 89-106
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Governance and conflict resolution in multi-use forests require the integration of stakeholders and decision-makers in multiple sectors: forestry, reindeer husbandry, conservation, tourism and local use. To a large extent, these sectors are characterised by divergent interests and considerable power discrepancies. Drawing upon semi-structured interviews in Gällivare, a municipality in northernmost Sweden, this paper discusses adaptive capacity with regard to interaction between sectors. The chapter examines impacts of the different land uses on each other, identifies adaptation options, and describes existing interaction measures. The chapter concludes that adaptive capacity at the local level is constrained by a number of factors, one example being the institutionalised character of reindeer herding–forestry relations that may limit adaptation at the local level.
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| 12617. |
- Keskitalo, E. Carina H., 1974-
(författare)
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Arktis är inget undantag
- 2009
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Ingår i: Polarår. - Stockholm : Svenska sällskapet för antropologi och geografi. ; , s. 219-234
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12618. |
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| 12619. |
- Keskitalo, E. Carina H., 1974-
(författare)
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Climate change adaptation in the United Kingdom : England and South-East England
- 2010
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Ingår i: Developing Adaptation Policy and Practice in Europe. - Dordrecht : Springer Netherlands. - 9789048193257 - 9789048193240 ; , s. 97-147
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The UK has been one of the early actors in developing adaptation to climate change, and today has a comprehensive legislative and regulative framework for including climate change effects in planning This chapter reviews the development of the UK approach, drawing on a literature study and semi-structured interviews conducted with several actors, the majority of whom are from public administration at the national, regional and local levels The study focuses on England and the South-East England region in particular, one of the areas most at risk of flooding and sea level rise in the UK In addition to discussing the national and regional levels, the chapter describes how adaptation has been integrated in a number of counties, cities and boroughs in the area All in all, the study reveals a relatively developed approach to adaptation, made possible in part as a result of both the recognised sensitivity of selected areas to climate change and the centralised nature of the political system Centralised as well as network capacities of the central government have made it possible for the national level to both include adaptation criteria in the performance assessment framework for local authorities, and for these to be broadly accepted among affected actors.
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| 12620. |
- Keskitalo, E Carina H, 1974-
(författare)
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Climate change, vulnerability and adaptive capacity in a multi-use forest municipality in Northern Sweden
- 2010
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Ingår i: Community adaptation and vulnerability in arctic regions. - Dordrecht : Springer Netherlands. ; , s. 285-311
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The impacts of climate change may be especially large on areas where conflicts regarding renewable resources such as multi-use forests already exist, and may increasingly impact sectors where access to resources is already limited. Drawing upon the CAVIAR framework for analysing current and future exposure-sensitivity and adaptive capacity in Gallivare municipality, northern Sweden, this chapter describes the socio-economic and environmental context of, and current and potential adaptations to, changes in forestry, reindeer husbandry, and winter tourism. The chapter concludes that these land use sectors are impacted by considerable economic and market pressures, with the result that conflicts between sectors have become increasingly pronounced. While climate change will eventually affect all land use sectors, impacts may be felt most immediately by those with the smallest existing margins for their activities, such as reindeer husbandry.
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