| 1. |
- Cortés, Marisol, et al.
(författare)
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CK2 oppositely modulates L-DOPA-induced dyskinesia via striatal projection neurons expressing D1 or D2 receptors
- 2017
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Ingår i: The Journal of Neuroscience. - 0270-6474. ; 37:49, s. 11930-11946
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1 and adenosine A2A receptor signaling in the striatum. Ablation of CK2 in D1 receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2A antagonist, caffeine. Because both, D1 and A2A receptors, play major roles in the cellular responses toL-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects ofL-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson’s disease. We report here that knock-out of CK2 in striatonigral neurons reduces the severity ofL-DOPA-induced dyskinesia (LID), a finding that correlates with lowered pERK but unchanged pPKA substrate levels in D1 medium spiny neurons as well as in cholinergic interneurons. In contrast, lack of CK2 in striatopallidal neurons enhances LID and ERK phosphorylation. Coadministration of caffeine with a low dose ofL-DOPA reduces dyskinesia in animals with striatopallidal knock-out to wild-type levels, suggesting a dependence on adenosine receptor activity. We also detect reduced Golf levels in the striatonigral but not in the striatopallidal knock-out in response toL-DOPA treatment. Our work shows, in a rodent model of PD, that treatment-induced dyskinesia and striatal ERK activation are bidirectionally modulated by ablating CK2 in D1- or D2-positive projection neurons, in male and female mice. The results reveal that CK2 regulates signaling events critical to LID in each of the two main populations of striatal neurons.
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| 2. |
- Edwards, Robert A., et al.
(författare)
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Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
- 2019
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
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Tidskriftsartikel (refereegranskat)abstract
- Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
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| 3. |
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| 4. |
- Sedlacek, Janosch, et al.
(författare)
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Evolutionary potential in the Alpine: trait heritabilities and performance variation of the dwarf willow Salix herbacea from different elevations and microhabitats
- 2016
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:12, s. 3940-3952
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Tidskriftsartikel (refereegranskat)abstract
- Alpine ecosystems are seriously threatened by climate change. One of the key mechanisms by which plants can adapt to changing environmental conditions is through evolutionary change. However, we still know little about the evolutionary potential in wild populations of long-lived alpine plants. Here, we investigated heritabilities of phenological traits, leaf size, and performance traits in natural populations of the long-lived alpine dwarf shrub Salix herbacea using relatedness estimates inferred from SSR (Simple Sequence Repeat) markers. Salix herbacea occurs in early-and late-snowmelt microhabitats (ridges and snowbeds), and we assessed how performance consequences of phenological traits and leaf size differ between these microhabitats in order to infer potential for evolutionary responses. Salix herbacea showed low, but significant, heritabilities of leaf size, clonal and sexual reproduction, and moderate heritabilities of phenological traits. In both microhabitats, we found that larger leaves, longer intervals between snowmelt and leaf expansion, and longer GDD (growing-degree days) until leaf expansion resulted in a stronger increase in the number of stems (clonal reproduction). In snowbeds, clonal reproduction increased with a shorter GDD until flowering, while the opposite was found on ridges. Furthermore, the proportion of flowering stems increased with GDD until flowering in both microhabitats. Our results suggest that the presence of significant heritable variation in morphology and phenology might help S. herbacea to adapt to changing environmental conditions. However, it remains to be seen if the rate of such an evolutionary response can keep pace with the rapid rate of climate change.
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| 5. |
- Sedlacek, Janosch, et al.
(författare)
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The Response of the Alpine Dwarf Shrub Salix herbacea to Altered Snowmelt Timing : Lessons from a Multi-Site Transplant Experiment
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is altering spring snowmelt patterns in alpine and arctic ecosystems, and these changes may alter plant phenology, growth and reproduction. To predict how alpine plants respond to shifts in snowmelt timing, we need to understand trait plasticity, its effects on growth and reproduction, and the degree to which plants experience a home-site advantage. We tested how the common, long-lived dwarf shrub Salix herbacea responded to changing spring snowmelt time by reciprocally transplanting turfs of S. herbacea between early-exposure ridge and late-exposure snowbed microhabitats. After the transplant, we monitored phenological, morphological and fitness traits, as well as leaf damage, during two growing seasons. Salix herbacea leafed out earlier, but had a longer development time and produced smaller leaves on ridges relative to snowbeds. Longer phenological development times and smaller leaves were associated with reduced sexual reproduction on ridges. On snowbeds, larger leaves and intermediate development times were associated with increased clonal reproduction. Clonal and sexual reproduction showed no response to altered snowmelt time. We found no home-site advantage in terms of sexual and clonal reproduction. Leaf damage probability depended on snowmelt and thus exposure period, but had no short-term effect on fitness traits. We conclude that the studied populations of S. herbacea can respond to shifts in snowmelt by plastic changes in phenology and leaf size, while maintaining levels of clonal and sexual reproduction. The lack of a home-site advantage suggests that S. herbacea may not be adapted to different microhabitats. The studied populations are thus unlikely to react to climate change by rapid adaptation, but their responses will also not be constrained by small-scale local adaptation. In the short term, snowbed plants may persist due to high stem densities. However, in the long term, reduction in leaf size and flowering, a longer phenological development time and increased exposure to damage may decrease overall performance of S. herbacea under earlier snowmelt.
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| 6. |
- Wheeler, Julia A., et al.
(författare)
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The snow and the willows : earlier spring snowmelt reduces performance in the low-lying alpine shrub Salix herbacea
- 2016
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 104:4, s. 1041-1050
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Tidskriftsartikel (refereegranskat)abstract
- Current changes in shrub abundance in alpine and arctic tundra ecosystems are primarily driven by climate change. However, while taller shrub communities are expanding, dwarf shrub communities show reductions under climate warming, and the mechanisms driving the latter (such as warming temperatures or accelerated spring snowmelt) may be complex. To determine and disentangle the response of a widespread arctic-alpine prostrate dwarf shrub to both climate warming and changes in snowmelt time, we investigated phenology, clonal and sexual reproduction, leaf size, wood tissue carbon balance and leaf damage in 480 patches of Salix herbacea, along its elevational and snowmelt microhabitat range over 3years in a space-for-time substitution. Earlier snowmelt was associated with longer phenological development periods, an increased likelihood of herbivory and fungal damage, lower stem density, smaller leaves and lower end-of-season wood reserve carbohydrates. Furthermore, while early snowmelt was associated with an increased proportion of flowering stems, the proportion of fruiting stems was not, as fruit set decreased significantly with earlier snowmelt. Warmer temperatures at lower elevations were associated with lower stem numbers and larger leaves.Synthesis. Our study indicates that phenology, fitness proxies and fungal/insect damage of the dwarf shrub S.herbacea are strongly influenced by snowmelt timing, and that earlier spring snowmelt reduced performance in S.herbacea. The likely mechanisms for many of the observed patterns are related to adverse temperature conditions in the early growing season. Reductions in clonal (stem number) and sexual reproduction (reduced fruit set) under earlier snowmelt, in addition to increasing damage probability, will likely lead to lower fitness and poorer performance, particularly in shrubs growing in early-exposure microhabitats. Further, we saw few concurrent benefits of higher temperatures for S.herbacea, particularly as warming was associated with lower clonal growth. As growing seasons become warmer and longer in arctic and alpine tundra ecosystems, early snowmelt is a critical mechanism reducing fitness and performance in a widespread dwarf shrub and may ultimately reduce dwarf shrub communities in tundra biomes.
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