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| 2. |
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| 3. |
- Savage, J. E., et al.
(författare)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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| 4. |
- Burrascano, S., et al.
(författare)
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Where are we now with European forest multi-taxon biodiversity and where can we head to?
- 2023
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Ingår i: Biological Conservation. - 0006-3207. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were repre-sented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multi-taxon studies are biased towards mature forests and may underrepresent the species related to other develop-mental phases. European forest compositional categories were all represented, but beech forests were over-represented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM stra-tegies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM in-dicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information.
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| 6. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 8. |
- Schindler, S., et al.
(författare)
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Multifunctionality of floodplain landscapes : Relating management options to ecosystem services
- 2014
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Ingår i: Landscape Ecology. - : Springer Science and Business Media LLC. - 0921-2973 .- 1572-9761. ; 29:2, s. 229-244
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Tidskriftsartikel (refereegranskat)abstract
- The concept of green infrastructure has been recently taken up by the European Commission for ensuring the provision of ecosystem services (ESS). It aims at the supply of multiple ESS in a given landscape, however, the effects of a full suite of management options on multiple ESS and landscape multifunctionality have rarely been assessed. In this paper we use European floodplain landscapes as example to develop an expert based qualitative conceptual model for the assessment of impacts of landscape scale interventions on multifunctionality. European floodplain landscapes are particularly useful for such approach as they originally provided a high variety and quantity of ESS that has declined due to the strong human impact these landscapes have experienced. We provide an overview of the effects of floodplain management options on landscape multifunctionality by assessing the effects of 38 floodplain management interventions on 21 relevant ESS, as well as on overall ESS supply. We found that restoration and rehabilitation consistently increased the multifunctionality of the landscape by enhancing supply of provisioning, regulation/maintenance, and cultural services. In contrast, conventional technical regulation measures and interventions related to extraction, infrastructure and intensive land use cause decrease in multifunctionality and negative effects for the supply of all three aspects of ESS. The overview of the effects of interventions shall provide guidance for decision makers at multiple governance levels. The presented conceptual model could be effectively applied for other landscapes that have potential for a supply of a high diversity of ESS. © 2014 Springer Science+Business Media Dordrecht.
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| 9. |
- Nooijen, C. F., et al.
(författare)
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Working mechanisms of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury
- 2016
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 48:7, s. 583-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In order to unravel the working mechanisms that underlie the effectiveness of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury, the aim of this study was to assess the mediating effects of physical and psychosocial factors on the intervention effect on physical activity. DESIGN: Randomized controlled trial. SETTING: Four rehabilitation centres in the Netherlands. SUBJECTS: Thirty-nine persons with subacute spinal cord injury. INTERVENTION: Behavioural intervention promoting an active lifestyle, based on motivational interviewing. The intervention involved a total of 13 individual sessions beginning 2 months before and ending 6 months after discharge from initial inpatient rehabilitation. MAIN MEASURES: The potential mediating effects of fatigue, pain, depression, illness cognition, exercise self-efficacy, coping and social support on the effect of the behavioural intervention on objectively measured physical activity (B = 0.35 h, p < 0.01) were studied. Measurements were performed at baseline, discharge, 6 months and 1 year after discharge. RESULTS: No single factor was found that strongly mediated the effect of the behavioural intervention on physical activity; however, multiple factors could partly explain the effect. Mediating effects greater than 10% were found for proactive coping (17.6%), exercise self-efficacy (15.9%), pain disability (15.3%) and helplessness (12.5%). DISCUSSION: Proactive coping (the ability to anticipate and deal with potential threats before they occur), exercise self-efficacy (self-confidence with respect to performing exercise and daily physical activities), pain disability (interference by pain of daily activities) and helplessness (emphasizing the aversive meaning of the disease) are important concepts in interventions promoting physical activity in persons with subacute spinal cord injury.
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| 10. |
- Schindler, S., et al.
(författare)
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Floodplain management in temperate regions : Is multifunctionality enhancing biodiversity?
- 2013
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Ingår i: Environmental Evidence. - : BioMed Central Ltd.. - 2047-2382. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Floodplains are among the most diverse, dynamic, productive and populated but also the most threatened ecosystems on Earth. Threats are mainly related to human activities that alter the landscape and disrupt fluvial processes to obtain benefits related to multiple ecosystem services (ESS). Floodplain management therefore requires close coordination among interest groups with competing claims and poses multi-dimensional challenges to policy-makers and project managers. The European Commission proposed in its recent Biodiversity Strategy to maintain and enhance European ecosystems and their services by establishing green infrastructure (GI). GI is assumed to provide multiple ecosystem functions and services including the conservation of biodiversity in the same spatial area. However, evidence for biodiversity benefits of multifunctional floodplain management is scattered and has not been synthesised. Methods/design: This protocol specifies the methods for conducting a systematic review to answer the following policy-relevant questions: a) what is the impact of floodplain management measures on biodiversity; b) how does the impact vary according to the level of multifunctionality of the measures; c) is there a difference in the biodiversity impact of floodplain management across taxa; d) what is the effect of the time since implementation on the impact of the most important measures; and e) are there any other factors that significantly modify the biodiversity impact of floodplain management measures? Within this systematic review we will assess multifunctionality in terms of ESS that are affected by an implemented intervention. Biodiversity indicators included in this systematic review will be related to the diversity, richness and abundance of species, other taxa or functional groups. We will consider if organisms are typical for and native to natural floodplain ecosystems. Specific inclusion criteria have been developed and the wide range of quality of primary literature will be evaluated with a tailor-made system for assessing susceptibility to bias and the reliability of the studies. The review is intended to bridge the science-policy interface and will provide a useful synthesis of knowledge for decision-makers at all governance levels. © 2013 Schindler et al.; licensee BioMed Central Ltd.
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| 11. |
- Schindler, S., et al.
(författare)
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Multifunctional floodplain management and biodiversity effects : a knowledge synthesis for six European countries
- 2016
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Ingår i: Biodiversity and Conservation. - : Springer Netherlands. - 0960-3115 .- 1572-9710. ; 25:7, s. 1349-1382
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Tidskriftsartikel (refereegranskat)abstract
- Floodplain ecosystems are biodiversity hotspots and supply multiple ecosystem services. At the same time they are often prone to human pressures that increasingly impact their intactness. Multifunctional floodplain management can be defined as a management approach aimed at a balanced supply of multiple ecosystem services that serve the needs of the local residents, but also those of off-site populations that are directly or indirectly impacted by floodplain management and policies. Multifunctional floodplain management has been recently proposed as a key concept to reconcile biodiversity and ecosystem services with the various human pressures and their driving forces. In this paper we present biophysics and management history of floodplains and review recent multifunctional management approaches and evidence for their biodiversity effects for the six European countries Ireland, the Netherlands, Germany, Slovakia, Hungary and the Ukraine. Multifunctional use of floodplains is an increasingly important strategy in some countries, for instance in the Netherlands and Hungary, and management of floodplains goes hand in hand with sustainable economic activities resulting in flood safety and biodiversity conservation. As a result, biodiversity is increasing in some of the areas where multifunctional floodplain management approaches are implemented. We conclude that for efficient use of management resources and ecosystem services, consensual solutions need to be realized and biodiversity needs to be mainstreamed into management activities to maximize ecosystem service provision and potential human benefits. Multifunctionality is more successful where a broad range of stakeholders with diverse expertise and interests are involved in all stages of planning and implementation.
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| 12. |
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| 13. |
- Nooijen, Carla F., et al.
(författare)
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Exercise self-efficacy and the relation with physical behavior and physical capacity in wheelchair-dependent persons with subacute spinal cord injury
- 2015
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Ingår i: Journal of NeuroEngineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 12, s. 103-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since physical activity and exercise levels are known to be generally low in persons with spinal cord injury (SCI), there seems to be a need for intervention. Exercise self-efficacy (ESE), the confidence persons have in their ability to be physically active and exercise, is an important and modifiable predictor of physical behavior. The goal of this study was to 1) describe ESE in persons with subacute SCI, 2) to assess ESE in subgroups based on demographic and lesion characteristics, and 3) to explore the relation between ESE and physical behavior and physical capacity. METHODS: Thirthy-seven persons with subacute SCI who are wheelchair dependent participated. Participants completed the Exercise Self-Efficacy Scale. We recorded age and lesion characteristics, measured physical behavior (physical activity, motility and sedentary day time, n = 35) with an accelerometer-based activity monitor and measured physical capacity (peak power output, n = 28 and peak oxygen uptake, n = 24) during a maximal hand-cycling test. Measurements were performed 2 months prior to discharge from inpatient rehabilitation. Mann-Whitney tests were used to test for differences between subgroups based on age and lesion characteristics and spearman correlations were used to assess the relation between ESE and physical activity and physical capacity. RESULTS: Persons with tetraplegia had lower ESE compared to persons with paraplegia (Z = -1.93, p = 0.05). No differences in ESE were found between subgroups based on age and motor completeness of the lesion. In persons with paraplegia, ESE was positively related to peak power output (rho = 0.58, p = 0.02). The relation of ESE with wheeled physical activity was rho = 0.36, p = 0.09. CONCLUSIONS: In persons with SCI who are dependent on a manual wheelchair, lesion level when categorized as paraplegic and tetraplegic affected ESE whereas age categories and completeness categories did not. Persons with tetraplegia were found to have lower confidence with regard to physical activity and exercise indicating that this subgroup can benefit from extra attention in the promotion of physical activity and exercise. In persons with paraplegia, ESE seemed to be lower in persons with less peak power output and less daily physical activity.
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| 14. |
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| 15. |
- Kakkar, Vaishali, et al.
(författare)
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The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model
- 2016
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765. ; 62:2, s. 272-283
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Tidskriftsartikel (refereegranskat)abstract
- Expanded CAG repeats lead to debilitating neurodegenerative disorders characterized by aggregation of proteins with expanded polyglutamine (polyQ) tracts. The mechanism of aggregation involves primary and secondary nucleation steps. We show how a noncanonical member of the DNAJ-chaperone family, DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by suppressing primary nucleation. This inhibition is mediated by a serine/threonine-rich region that provides an array of surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bonds essential for the stability of amyloid fibrils. Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and leads to delayed neurite retraction even before aggregates are visible. In a mouse model, brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifespan, pointing to DNAJB6 as a potential target for disease therapy and tool for unraveling early events in the onset of polyQ diseases. Kakkar et al. show that DNAJB6 is a chaperone that inhibits early steps in the formation of polyQ amyloid fibrils. An S/T-rich region in DNAJB6 is crucial for this function. In a polyQ mouse model, the inhibitory effects of DNAJB6 delay disease onset and increase lifespan.
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| 16. |
- Northcott, Paul A, et al.
(författare)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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