| 1. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 3. |
- Morales, J. C., et al.
(författare)
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A giant exoplanet orbiting a very-low-mass star challenges planet formation models
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6460, s. 1441-1445
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Tidskriftsartikel (refereegranskat)abstract
- Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.
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| 4. |
- van Zessen, R., et al.
(författare)
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Cue and Reward Evoked Dopamine Activity Is Necessary for Maintaining Learned Pavlovian Associations
- 2021
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 41:23, s. 5004-5014
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Tidskriftsartikel (refereegranskat)abstract
- Associating natural rewards with predictive environmental cues is crucial for survival. Dopamine (DA) neurons of the ventral tegmental area (VTA) are thought to play a crucial role in this process by encoding reward prediction errors (RPEs) that have been hypothesized to play a role in associative learning. However, it is unclear whether this signal is still necessary after animals have acquired a cue-reward association. In order to investigate this, we trained mice to learn a Pavlovian cue-reward association. After learning, mice show robust anticipatory and consummatory licking behavior. As expected, calcium activity of VTA DA neurons goes up for cue presentation as well as reward delivery. Optogenetic inhibition during the moment of reward delivery disrupts learned behavior, even in the continued presence of reward. This effect is more pronounced over trials and persists on the next training day. Moreover, outside of the task licking behavior and locomotion are unaffected. Similarly to inhibitions during the reward period, we find that inhibiting cue-induced dopamine (DA) signals robustly decreases learned licking behavior, indicating that cue-related DA signals are a potent driver for learned behavior. Overall, we show that inhibition of either of these DA signals directly impairs the expression of learned associative behavior. Thus, continued DA signaling in a learned state is necessary for consolidating Pavlovian associations.
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| 5. |
- Flaberg, E., et al.
(författare)
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High-throughput live cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts
- 2011
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 128:12, s. 2793-2802
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297-310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high-throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co-cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40-transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high-throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.
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| 6. |
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| 7. |
- Schinnerer, Eva, et al.
(författare)
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PHANGS-JWST First Results : Rapid Evolution of Star Formation in the Central Molecular Gas Ring of NGC 1365
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale bars can fuel galaxy centers with molecular gas, often leading to the development of dense ringlike structures where intense star formation occurs, forming a very different environment compared to galactic disks. We pair ∼0.″3 (30 pc) resolution new JWST/MIRI imaging with archival ALMA CO(2-1) mapping of the central ∼5 kpc of the nearby barred spiral galaxy NGC 1365 to investigate the physical mechanisms responsible for this extreme star formation. The molecular gas morphology is resolved into two well-known bright bar lanes that surround a smooth dynamically cold gas disk (R gal ∼ 475 pc) reminiscent of non-star-forming disks in early-type galaxies and likely fed by gas inflow triggered by stellar feedback in the lanes. The lanes host a large number of JWST-identified massive young star clusters. We find some evidence for temporal star formation evolution along the ring. The complex kinematics in the gas lanes reveal strong streaming motions and may be consistent with convergence of gas streamlines expected there. Indeed, the extreme line widths are found to be the result of inter-“cloud” motion between gas peaks; ScousePy decomposition reveals multiple components with line widths of 〈σ CO,scouse〉 ≈ 19 km s−1 and surface densities of 〈 Σ H 2 , scouse 〉 ≈ 800 M ⊙ pc − 2 , similar to the properties observed throughout the rest of the central molecular gas structure. Tailored hydrodynamical simulations exhibit many of the observed properties and imply that the observed structures are transient and highly time-variable. From our study of NGC 1365, we conclude that it is predominantly the high gas inflow triggered by the bar that is setting the star formation in its CMZ.
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| 8. |
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| 9. |
- Abbey-Lee, Robin, et al.
(författare)
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Does perceived predation risk affect patterns of extra-pair paternity? A field experiment in a passerine bird
- 2018
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Ingår i: Functional Ecology. - : WILEY. - 0269-8463 .- 1365-2435. ; 32:4, s. 1001-1010
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Tidskriftsartikel (refereegranskat)abstract
- Non-consumptive predator effects have been shown to influence a wide range of behavioural, life history and morphological traits. Extra-pair reproduction is widespread among socially monogamous birds and may incur predation costs. Consequently, altered rates of extra-pair reproduction are expected in circumstances characterized by increased adult perceived predation risk. In addition, extra-pair reproduction is expected to be most affected for birds with phenotypes that generally increase predation risk (such as more active individuals). In two consecutive years, perceived predation risk was manipulated for great tits Parus major breeding in 12 nest-box plots by broadcasting sounds of their main predator (European sparrowhawk Accipiter nisus; six plots). As a control treatment, sounds of a sympatric, avian non-predator species were broadcast (Eurasian blackbird Turdus merula; six plots). Levels of extra-pair paternity did not differ between plots with different predation risk treatments. Males that moved more in a novel environment (more active or faster exploring) tended to have offspring with fewer partners, but this effect did not vary with predation risk treatment. From an adaptive viewpoint, predation costs associated with extra-pair reproduction may be small and may not outweigh the benefits of extra-pair behaviour. Research on a broader range of taxa with different mating strategies is now needed to confirm the generality of our findings.
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| 10. |
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