| 1. |
- Patel, Y., et al.
(författare)
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
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Tidskriftsartikel (refereegranskat)abstract
- Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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| 2. |
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| 3. |
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| 4. |
- Wierenga, Lara M., et al.
(författare)
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Greater male than female variability in regional brain structure across the lifespan
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
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Tidskriftsartikel (refereegranskat)abstract
- For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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| 5. |
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| 6. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 7. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 8. |
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| 9. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 10. |
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| 11. |
- Forstner, A. J., et al.
(författare)
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Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
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Tidskriftsartikel (refereegranskat)abstract
- Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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| 12. |
- Adiels, Lars, 1952-, et al.
(författare)
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Test of CP violation with K0 and K‾0 at LEAR
- 1985
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Ingår i: Physics with antiprotons at LEAR in the ACOL era. - Gif sur Yvette : Editions Frontières. - 2863320351 ; , s. 467-482
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 13. |
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| 14. |
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| 15. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 16. |
- Pauli, H., et al.
(författare)
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Recent Plant Diversity Changes on Europe's Mountain Summits
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 336:6079, s. 353-355
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Tidskriftsartikel (refereegranskat)abstract
- In mountainous regions, climate warming is expected to shift species' ranges to higher altitudes. Evidence for such shifts is still mostly from revisitations of historical sites. We present recent (2001 to 2008) changes in vascular plant species richness observed in a standardized monitoring network across Europe's major mountain ranges. Species have moved upslope on average. However, these shifts had opposite effects on the summit floras' species richness in boreal-temperate mountain regions (+3.9 species on average) and Mediterranean mountain regions (-1.4 species), probably because recent climatic trends have decreased the availability of water in the European south. Because Mediterranean mountains are particularly rich in endemic species, a continuation of these trends might shrink the European mountain flora, despite an average increase in summit species richness across the region.
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| 17. |
- Staude, I. R., et al.
(författare)
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Directional turnover towards larger-ranged plants over time and across habitats
- 2022
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 466-82
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Tidskriftsartikel (refereegranskat)abstract
- Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.
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| 18. |
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| 19. |
- Lembrechts, Jonas J., et al.
(författare)
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SoilTemp : A global database of near-surface temperature
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
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Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
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| 20. |
- Winkler, M., et al.
(författare)
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The rich sides of mountain summits - a pan-European view on aspect preferences of alpine plants
- 2016
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270. ; 43:11, s. 2261-2273
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Tidskriftsartikel (refereegranskat)abstract
- Aim In the alpine life zone, plant diversity is strongly determined by local topography and microclimate. We assessed the extent to which aspect and its relatedness to temperature affect plant species diversity, and the colonization and disappearance of species on alpine summits on a pan-European scale. Methods Vascular plant species and their percentage cover were recorded in permanent plots in each cardinal direction on 123 summits in 32 regions across Europe. For a subset from 17 regions, resurvey data and 6-year soil temperature series were available. Differences in temperature sum and Shannon index as well as species richness, colonization and disappearance of species among cardinal directions were analysed using linear mixed-effects and generalised mixed-effects models, respectively. Results Temperature sums were higher in east-and south-facing aspects than in the north-facing ones, while the west-facing ones were intermediate; differences were smallest in northern Europe. The patterns of temperature sums among aspects were consistent among years. In temperate regions, thermal differences were reflected by plant diversity, whereas this relationship was weaker or absent on Mediterranean and boreal mountains. Colonization of species was positively related to temperature on Mediterranean and temperate mountains, whereas disappearance of species was not related to temperature. Main conclusions Thermal differences caused by solar radiation determine plant species diversity on temperate mountains. Advantages for plants on eastern slopes may result from the combined effects of a longer diurnal period of radiation due to convection cloud effects in the afternoon and the sheltered position against the prevailing westerly winds. In northern Europe, long summer days and low sun angles can even out differences among aspects. On Mediterranean summits, summer drought may limit species numbers on the warmer slopes. Warmer aspects support a higher number of colonization events. Hence, aspect can be a principal determinant of the pace of climate-induced migration processes.
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| 21. |
- Bashkanov, M., et al.
(författare)
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Two-pion production in proton-proton collisions
- 2004
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Ingår i: Hadron Spectroscopy, Tenth International Conference on Hadron Spectrscopy, Aschaffenburg, Germany 31 August - 6 September 2003. - 0735401977 ; , s. 241-244
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Burli, S., et al.
(författare)
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A common soil temperature threshold for the upper limit of alpine grasslands in European mountains
- 2021
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Ingår i: Alpine Botany. - : Springer Science and Business Media LLC. - 1664-2201 .- 1664-221X. ; 131, s. 41-52
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Tidskriftsartikel (refereegranskat)abstract
- While climatic research about treeline has a long history, the climatic conditions corresponding to the upper limit of closed alpine grasslands remain poorly understood. Here, we propose a climatic definition for this limit, the 'grassline', in analogy to the treeline, which is based on the growing season length and the soil temperature. Eighty-seven mountain summits across ten European mountain ranges, covering three biomes (boreal, temperate, Mediterranean), were inventoried as part of the GLORIA project. Vascular plant cover was estimated visually in 326 plots of 1 x 1 m. Soil temperatures were measured in situ for 2-7 years, from which the length of the growing season and mean temperature were derived. The climatic conditions corresponding to 40% plant cover were defined as the thresholds for alpine grassland. Closed vegetation was present in locations with a mean growing season soil temperature warmer than 4.9 degrees C, or a minimal growing season length of 85 days, with the growing season defined as encompassing days with daily mean >= 1 degrees C. Hence, the upper limit of closed grasslands was associated with a mean soil temperature close to that previously observed at the treeline, and in accordance with physiological thresholds to growth in vascular plants. In contrast to trees, whose canopy temperature is coupled with air temperature, small-stature alpine plants benefit from the soil warmed by solar radiation and consequently, they can grow at higher elevations. Since substrate stability is necessary for grasslands to occur at their climatic limit, the grassline rarely appears as a distinct linear feature.
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| 23. |
- Dullinger, S., et al.
(författare)
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Weak and variable relationships between environmental severity and small-scale co-occurrence in alpine plant communities
- 2007
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 95:6, s. 1284-1295
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Tidskriftsartikel (refereegranskat)abstract
- 1. The stress gradient hypothesis suggests a shift from predominant competition to facilitation along gradients of increasing environmental severity. This shift is proposed to cause parallel changes from prevailing spatial segregation to aggregation among the species within a community. 2. We used 904 1-m(2) plots, each subdivided into 100 10 x 10 cm, or 25 20 x 20 cm cells, respectively, from 67 European mountain summits grouped into 18 regional altitudinal transects, to test this hypothesized correlation between fine-scale spatial patterns and environmental severity. 3. The data were analysed by first calculating standardized differences between observed and simulated random co-occurrence patterns for each plot. These standardized effect sizes were correlated to indicators of environmental severity by means of linear mixed models. In a factorial design, separate analyses were made for four different indicators of environmental severity (the mean temperature of the coldest month, the temperature sum of the growing season, the altitude above tree line, and the percentage cover of vascular plants in the whole plot), four different species groups (all species, graminoids, herbs, and all growth forms considered as pseudospecies) and at the 10 x 10 cm and 20 x 20 cm grain sizes. 4. The hypothesized trends were generally weak and could only be detected by using the mean temperature of the coldest month or the percentage cover of vascular plants as the indicator of environmental severity. The spatial arrangement of the full species set proved more responsive to changes in severity than that of herbs or graminoids. The expected trends were more pronounced at a grain size of 10 x 10 cm than at 20 x 20 cm. 5. Synthesis. In European alpine plant communities the relationships between small-scale co-occurrence patterns of vascular plants and environmental severity are weak and variable. This variation indicates that shifts in net interactions with environmental severity may differ among indicators of severity, growth forms and scales. Recognition of such variation may help to resolve some of the current debate surrounding the stress gradient hypothesis.
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| 24. |
- Gottfried, M., et al.
(författare)
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Continent-wide response of mountain vegetation to climate change
- 2012
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 2:2, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- Climate impact studies have indicated ecological fingerprints of recent global warming across a wide range of habitats(1,2). Although these studies have shown responses from various local case studies, a coherent large-scale account on temperature-driven changes of biotic communities has been lacking(3,4). Here we use 867 vegetation samples above the treeline from 60 summit sites in all major European mountain systems to show that ongoing climate change gradually transforms mountain plant communities. We provide evidence that the more cold-adapted species decline and the more warm-adapted species increase, a process described here as thermophilization. At the scale of individual mountains this general trend may not be apparent, but at the larger, continental scale we observed a significantly higher abundance of thermophilic species in 2008, compared with 2001. Thermophilization of mountain plant communities mirrors the degree of recent warming and is more pronounced in areas where the temperature increase has been higher. In view of the projected climate change(5,6) the observed transformation suggests a progressive decline of cold mountain habitats and their biota.
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| 25. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 26. |
- Rayner, C, et al.
(författare)
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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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| 27. |
- Elvsashagen, T, et al.
(författare)
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The genetic architecture of human brainstem structures and their involvement in common brain disorders
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
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Tidskriftsartikel (refereegranskat)abstract
- Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Kontos, C, et al.
(författare)
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Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5981-
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Tidskriftsartikel (refereegranskat)abstract
- Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides (‘msR4Ms’) designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe−/− mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.
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| 32. |
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| 33. |
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| 34. |
- Zhang, W, et al.
(författare)
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INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood.MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA calledINflammatory MKL1InteractingLongNoncoding RNA (INKILN).INKILNexpression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation ofINKILNwas determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role ofINKILNin VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to studyINKLINexpression and function in ligation injury-induced neointimal formation.ResultsINKILNexpression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm.INKILNis transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter.INKILNactivates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically,INKILNphysically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway.INKILNdepletion blocks ILIβ-induced nuclear localization of both p65 and MKL1. Knockdown ofINKILNabolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further,INKILNknockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10.INKILNis induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice.ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving anINKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.
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| 35. |
- Blumenstock, T., et al.
(författare)
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Characterization and potential for reducing optical resonances in Fourier transform infrared spectrometers of the Network for the Detection of Atmospheric Composition Change (NDACC)
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:2, s. 1239-1252
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Tidskriftsartikel (refereegranskat)abstract
- Although optical components in Fourier transform infrared (FTIR) spectrometers are preferably wedged, in practice, infrared spectra typically suffer from the effects of optical resonances ("channeling") affecting the retrieval of weakly absorbing gases. This study investigates the level of channeling of each FTIR spectrometer within the Network for the Detection of Atmospheric Composition Change (NDACC). Dedicated spectra were recorded by more than 20 NDACC FTIR spectrometers using a laboratory mid-infrared source and two detectors. In the indium antimonide (InSb) detector domain (1900-5000 cm-1), we found that the amplitude of the most pronounced channeling frequency amounts to 0.1 ‰ to 2.0 ‰ of the spectral background level, with a mean of (0:68±0:48) ‰ and a median of 0.60 ‰. In the mercury cadmium telluride (HgCdTe) detector domain (700-1300 cm-1), we find even stronger effects, with the largest amplitude ranging from 0.3 ‰ to 21 ‰ with a mean of (2:45±4:50) ‰ and a median of 1.2 ‰. For both detectors, the leading channeling frequencies are 0.9 and 0.11 or 0.23 cm-1 in most spectrometers. The observed spectral frequencies of 0.11 and 0.23 cm-1 correspond to the optical thickness of the beam splitter substrate. The 0.9 cm-1 channeling is caused by the air gap in between the beam splitter and compensator plate. Since the air gap is a significant source of channeling and the corresponding amplitude differs strongly between spectrometers, we propose new beam splitters with the wedge of the air gap increased to at least 0.8. We tested the insertion of spacers in a beam splitter's air gap to demonstrate that increasing the wedge of the air gap decreases the 0.9 cm-1 channeling amplitude significantly. A wedge of the air gap of 0.8 reduces the channeling amplitude by about 50 %, while a wedge of about 2 removes the 0.9 cm-1 channeling completely. This study shows the potential for reducing channeling in the FTIR spectrometers operated by the NDACC, thereby increasing the quality of recorded spectra across the network.
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| 36. |
- Dengler, Juergen, et al.
(författare)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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Ingår i: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 37. |
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| 38. |
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| 39. |
- Jokipii-Lukkari, Soile, et al.
(författare)
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Dual targeted poplar ferredoxin NADP+ oxidoreductase interacts with hemoglobin 1
- 2016
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Ingår i: Plant Science. - : Elsevier BV. - 0168-9452. ; 247, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports have connected non-symbiotic and truncated hemoglobins (Hbs) to metabolism of nitric oxide (NO), an important signalling molecule involved in wood formation. We have studied the capability of poplar (Populus tremula × tremuloides) Hbs PttHb1 and PttTrHb proteins alone or with a flavin-protein reductase to relieve NO cytotoxicity in living cells. Complementation tests in a Hb-deficient, NO-sensitive yeast (Saccharomyces cerevisiae) δyhb1 mutant showed that neither PttHb1 nor PttTrHb alone protected cells against NO. To study the ability of Hbs to interact with a reductase, ferredoxin NADP+ oxidoreductase PtthFNR was characterized by sequencing and proteomics. To date, by far the greatest number of the known dual-targeted plant proteins are directed to chloroplasts and mitochondria. We discovered a novel variant of hFNR that lacks the plastid presequence and resides in cytosol. The coexpression of PttHb1 and PtthFNR partially restored NO resistance of the yeast δyhb1 mutant, whereas PttTrHb coexpressed with PtthFNR failed to rescue growth. YFP fusion proteins confirmed the interaction between PttHb1 and PtthFNR in plant cells. The structural modelling results indicate that PttHb1 and PtthFNR are able to interact as NO dioxygenase. This is the first report on dual targeting of central plant enzyme FNR to plastids and cytosol.
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| 40. |
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| 41. |
- Matricardi, PM, et al.
(författare)
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EAACI Molecular Allergology User's Guide
- 2016
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Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 2727 Suppl 23, s. 1-250
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Tidskriftsartikel (refereegranskat)
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| 42. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 43. |
- Ojala, Joonas, et al.
(författare)
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Reassigning the shapes of the 0+ states in the 186Pb nucleus
- 2022
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Ingår i: Communications Physics. - : Springer Science and Business Media LLC. - 2399-3650. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Across the physics disciplines, the 186Pb nucleus is the only known system, where the two first excited states, together with the ground state, form a triplet of zero-spin states assigned with prolate, oblate and spherical shapes. Here we report on a precision measurement where the properties of collective transitions in 186Pb were determined in a simultaneous in-beam γ-ray and electron spectroscopy experiment employing the recoil-decay tagging technique. The feeding of the 02+ state and the interband 22+→21+ transition have been observed. We also present direct measurement of the energies of the electric monopole transitions from the excited 0+ states to the 0+ ground state. In contrast to the earlier understanding, the obtained reduced transition probability B(E2;21+→02+) value of 190(80) W.u., the transitional quadrupole moment ∣Qt(21+→02+)∣=7.7(33) eb and intensity balance arguments provide evidence to reassign the 02+ and 03+ states with predominantly prolate and oblate shape, respectively. Our work demonstrates a step-up in experimental sensitivity and paves the way for systematic studies of electric monopole transitions in this region. These electric monopole transitions probe the nuclear volume in a unique manner and provide unexploited input for development of the next-generation energy density functional models.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Pelisek, J, et al.
(författare)
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Biobanking: Objectives, Requirements, and Future Challenges-Experiences from the Munich Vascular Biobank
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.
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| 48. |
- Schiele, Miriam A., et al.
(författare)
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Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders : A meta-analysis
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 44, s. 105-120
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Tidskriftsartikel (refereegranskat)abstract
- There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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| 49. |
- Thor, M, et al.
(författare)
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Temporal patterns of patient-reported trismus and associated mouth-opening distances in radiotherapy for head and neck cancer: A prospective cohort study.
- 2018
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Ingår i: Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. - : Wiley. - 1749-4486. ; 43:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- To identify temporal patterns of patient-reported trismus during the first year post-radiotherapy, and to study their associations with maximal interincisal opening distances (MIOs).Single institution case series.University hospital ENT clinic.One hundred and ninety-six subjects who received radiotherapy (RT) for head and neck cancer (HNC) with or without chemotherapy in 2007-2012 to a total dose of 64.6/68Gy in 38/34 fractions, respectively. All subjects were prospectively assessed for mouth-opening ability (Gothenburg Trismus Questionnaire (GTQ), European Organization for Research and Treatment of Cancer quality of life Questionnaire (EORTC QLQ-H&N35), and MIO) pre-RT and at 3, 6 and 12months after RT.Correlations between temporally robust GTQ symptoms and MIO as given by Pearson's correlation coefficients (Pr ); temporally robust GTQ-symptom domains as given by factor analysis; rates of trismus with respect to baseline by risk ratios (RRs).Four temporally robust domains were identified: Eating (3-7 symptoms), Jaw (3-7), Pain (2-5) and Quality of Life (QoL, 2-5), and included 2-3 persistent symptoms across all post-RT assessments. The median RR for a moderate/severe (>2/>3) cut-off was the highest for Jaw (3.7/3.6) and QoL (3.2/2.9). The median Pr between temporally robust symptoms and MIO post-radiotherapy was 0.25-0.35/0.34-0.43/0.24-0.31/0.34-0.50 for Eating/Jaw/Pain/QoL, respectively.Mouth-opening distances in patients with HNC post-RT can be understood in terms of associated patient-reported outcomes on trismus-related difficulties. Our data suggest that a reduction in MIO can be expected as patients communicate their mouth-opening status to interfere with private/social life, a clinical warning signal for emerging or worsening trismus as patients are being followed after RT.
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| 50. |
- van Ree, R, et al.
(författare)
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The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification.
- 2008
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 63:3, s. 310-26
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Tidskriftsartikel (refereegranskat)abstract
- Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.
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