| 1. |
- Guipponi, Michel, et al.
(författare)
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Galanin pathogenic mutations in temporal lobe epilepsy
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:11, s. 3082-3091
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Tidskriftsartikel (refereegranskat)abstract
- Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.
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| 2. |
- Kjellström, Erik, 1967-, et al.
(författare)
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Contributions from Changing Large-Scale Atmospheric Conditions to Changes in Scandinavian Temperature and Precipitation Between Two Climate Normals
- 2022
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Ingår i: Tellus. Series A, Dynamic meteorology and oceanography. - : Stockholm University Press. - 0280-6495 .- 1600-0870. ; 74, s. 204-221
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Tidskriftsartikel (refereegranskat)abstract
- Multidecadal changes in regional climate can occur as a forced response to changing greenhouse gases and aerosols, as a result of natural internal climate variability, or due to their combination. Internal climate variability is frequently associated with regional changes in large-scale circulation. We investigate how changes in Scandinavian temperature and precipitation conditions during 1961–2020 can be linked to changes in the atmospheric large-scale circulation. The study is based on data from the ERA5 reanalysis and on Swedish average conditions based on observations from the Swedish Meteorological and Hydrological Institute. In general, it is shown that all seasons have become warmer and there is a predominance for more precipitation in the last 30 years. The results also show a clear decrease in daily temperature variability for winter and an increase in summer while there is no similar systematic change for precipitation. Further, we use a circulation type classification technique for identifying ten different circulation types for each calendar month in the 1961–2020 period. Results indicate that changes between the two periods can partly be related to changes in large-scale circulation due to changes in the frequencies of different circulation types. However, it is also clear that the contribution from frequency-related changes to the total change is comparatively low for most months and that changes also within the circulation types are required to explain the total change. The main conclusion of the study is that during the last 30 years it has mostly been warmer than in the preceding 30 years for the same type of weather situation for all months in the year. Consequently, internal climate variability, as represented by changes in the large-scale atmospheric circulation, cannot explain the observed changes in the Scandinavian temperature and precipitation.
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| 3. |
- Martin-Puertas, Celia, et al.
(författare)
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Regional atmospheric circulation shifts induced by a grand solar minimum
- 2012
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Ingår i: Nature Geoscience. - 1752-0908 .- 1752-0894. ; 5:6, s. 397-401
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Tidskriftsartikel (refereegranskat)abstract
- Large changes in solar ultraviolet radiation can indirectly affect climate(1) by inducing atmospheric changes. Specifically, it has been suggested that centennial-scale climate variability during the Holocene epoch was controlled by the Sun(2,3). However, the amplitude of solar forcing is small when compared with the climatic effects and, without reliable data sets, it is unclear which feedback mechanisms could have amplified the forcing. Here we analyse annually laminated sediments of Lake Meerfelder Maar, Germany, to derive variations in wind strength and the rate of Be-10 accumulation, a proxy for solar activity, from 3,300 to 2,000 years before present. We find a sharp increase in windiness and cosmogenic Be-10 deposition 2,759 +/- 39 varve years before present and a reduction in both entities 199 +/- 9 annual layers later. We infer that the atmospheric circulation reacted abruptly and in phase with the solar minimum. A shift in atmospheric circulation in response to changes in solar activity is broadly consistent with atmospheric circulation patterns in long-term climate model simulations, and in reanalysis data that assimilate observations from recent solar minima into a climate model. We conclude that changes in atmospheric circulation amplified the solar signal and caused abrupt climate change about 2,800 years ago, coincident with a grand solar minimum.
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