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- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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- Reinbold, C. S., et al.
(författare)
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Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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- Ou, Anna H., et al.
(författare)
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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
- 2024
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Ingår i: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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- Anderson, J. K., et al.
(författare)
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Grouping of PFAS for human health risk assessment : Findings from an independent panel of experts
- 2022
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
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9. |
- De Frenne, P., et al.
(författare)
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A latitudinal gradient in seed nutrients of the forest herb Anemone nemorosa
- 2011
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Ingår i: Plant Biology. - : Wiley. - 1435-8603 .- 1438-8677. ; 13:3, s. 493-501
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Tidskriftsartikel (refereegranskat)abstract
- The nutrient concentration in seeds determines many aspects of potential success of the sexual reproductive phase of plants, including the seed predation probability, efficiency of seed dispersal and seedling performance. Despite considerable research interest in latitudinal gradients of foliar nutrients, a similar gradient for seeds remains unexplored. We investigated a potential latitudinal gradient in seed nutrient concentrations within the widespread European understorey forest herb Anemone nemorosa L. We sampled seeds of A. nemorosa in 15 populations along a 1900-km long latitudinal gradient at three to seven seed collection dates post-anthesis and investigated the relative effects of growing degree-hours > 5 degrees C, soil characteristics and latitude on seed nutrient concentrations. Seed nitrogen, nitrogen:phosphorus ratio and calcium concentration decreased towards northern latitudes, while carbon:nitrogen ratios increased. When taking differences in growing degree-hours and measured soil characteristics into account and only considering the most mature seeds, the latitudinal decline remained particularly significant for seed nitrogen concentration. We argue that the decline in seed nitrogen concentration can be attributed to northward decreasing seed provisioning due to lower soil nitrogen availability or greater investment in clonal reproduction. This pattern may have large implications for the reproductive performance of this forest herb as the degree of seed provisioning ultimately co-determines seedling survival and reproductive success.
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- De Frenne, P, et al.
(författare)
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Significant effects of temperature on the reproductive output of the forest herb Anemone nemorosa L.
- 2010
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 259:4, s. 809-817
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming is already influencing plant migration in different parts of the world.Numerous modelshave been developed to forecast future plant distributions. Few studies, however, have investigated thepotential effect of warming on the reproductive output of plants. Understorey forest herbs in particular,have received little attention in the debate on climate change impacts.This study focuses on the effect of temperature on sexual reproductive output (number of seeds, seedmass, germination percentage and seedling mass) of Anemone nemorosa L., a model species for slowcolonizing herbaceous forest plants. We sampled seeds of A. nemorosa in populations along a 2400 kmlatitudinal gradient from northern France to northern Sweden during three growing seasons (2005, 2006and 2008). This study design allowed us to isolate the effects of accumulated temperature (GrowingDegree Hours; GDH) from latitude and the local abiotic and biotic environment. Germination and seedsowing trials were performed in incubators, a greenhouse and under field conditions in a forest. Finally,we disentangled correlations between the different reproductive traits of A. nemorosa along thelatitudinal gradient.We found a clear positive relationship between accumulated temperature and seed and seedlingtraits: reproductive output of A. nemorosa improved with increasing GDH along the latitudinal gradient.Seedmass and seedling mass, for instance, increased by 9.7% and 10.4%, respectively, for every 1000 8C hincrease in GDH.Wealso derived strong correlations between several seed and seedling traits both underfield conditions and in incubators. Our results indicate that seed mass, incubator-based germinationpercentage (Germ%Inc) and the output of germinable seeds (product of number of seeds and Germ%Incdivided by 100) from plants grown along a latitudinal gradient (i.e. at different temperature regimes)provide valuable proxies to parameterize key population processes in models.We conclude that (1) climate warming may have a pronounced positive impact on sexualreproduction of A. nemorosa and (2) climate models forecasting plant distributions would benefit fromincluding the temperature sensitivity of key seed traits and population processes.
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