| 1. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 2. |
- Pittman, S. J., et al.
(författare)
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Seascape ecology : identifying research priorities for an emerging ocean sustainability science
- 2021
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Ingår i: Marine Ecology Progress Series. - : INTER-RESEARCH. - 0171-8630 .- 1616-1599. ; 663, s. 1-29
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Tidskriftsartikel (refereegranskat)abstract
- Seascape ecology, the marine-centric counterpart to landscape ecology, is rapidly emerging as an interdisciplinary and spatially explicit ecological science with relevance to marine management, bio-diversity conservation, and restoration. While important progress in this field has been made in the past decade, there has been no coherent prioritisation of key research questions to help set the future research agenda for seascape ecology. We used a 2-stage modified Delphi method to solicit applied research questions from academic experts in seascape ecology and then asked respondents to identify priority questions across 9 interrelated research themes using 2 rounds of selection. We also invited senior management/conservation practitioners to prioritise the same research questions. Analyses highlighted congruence and discrepancies in perceived priorities for applied research. Themes related to both ecological concepts and management practice, and those identified as priorities include seascape change, seascape connectivity, spatial and temporal scale, ecosystem-based management, and emerging technologies and metrics. Highest-priority questions (upper tercile) received 50% agreement between respondent groups, and lowest priorities (lower tercile) received 58% agreement. Across all 3 priority tiers, 36 of the 55 questions were within a +/- 10% band of agreement. We present the most important applied research questions as determined by the proportion of votes received. For each theme, we provide a synthesis of the research challenges and the potential role of seascape ecology. These priority questions and themes serve as a roadmap for advancing applied seascape ecology during, and beyond, the UN Decade of Ocean Science for Sustainable Development (2021-2030).
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| 3. |
- Meyer, Esther, et al.
(författare)
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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
- 2017
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49, s. 223-237
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Tidskriftsartikel (refereegranskat)abstract
- Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
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| 4. |
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| 5. |
- Bodin, Örjan, et al.
(författare)
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Improving network approaches to the study of complex social–ecological interdependencies
- 2019
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:7, s. 551-559
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Tidskriftsartikel (refereegranskat)abstract
- Achieving effective, sustainable environmental governance requires a better understanding of the causes and consequences of the complex patterns of interdependencies connecting people and ecosystems within and across scales. Network approaches for conceptualizing and analysing these interdependencies offer one promising solution. Here, we present two advances we argue are needed to further this area of research: (i) a typology of causal assumptions explicating the causal aims of any given network-centric study of social–ecological interdependencies; (ii) unifying research design considerations that facilitate conceptualizing exactly what is interdependent, through what types of relationships and in relation to what kinds of environmental problems. The latter builds on the appreciation that many environmental problems draw from a set of core challenges that re-occur across contexts. We demonstrate how these advances combine into a comparative heuristic that facilitates leveraging case-specific findings of social–ecological interdependencies to generalizable, yet context-sensitive, theories based on explicit assumptions of causal relationships.
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| 6. |
- Deans, R., et al.
(författare)
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The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration
- 2023
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Ingår i: Australian & New Zealand Journal of Obstetrics & Gynaecology. - 0004-8666.
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe aim is to report the results of Australia's first uterus transplantation (UTx). MethodsFollowing long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. ResultsThis is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. ConclusionTwenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.
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| 7. |
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| 8. |
- Sayles, J. S., et al.
(författare)
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Social-ecological network analysis for sustainability sciences : a systematic review and innovative research agenda for the future
- 2019
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 14:9
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Forskningsöversikt (refereegranskat)abstract
- Social-ecological network (SEN) concepts and tools are increasingly used in human-environment and sustainability sciences. We take stock of this budding research area to further show the strength of SEN analysis for complex human-environment settings, identify future synergies between SEN and wider human-environment research, and provide guidance about when to use different kinds of SEN approaches and models. We characterize SEN research along a spectrum specifying the degree of explicit network representation of system components and dynamics. We then systematically review one end of this spectrum, what we term 'fully articulated SEN' studies, which specifically model unique social and ecological units and relationships. Results show a larger number of papers focus on methodological advancement and applied ends. While there has been some development and testing of theories, this remains an area for future work and would help develop SENs as a unique field of research, not just a method. Authors have studied diverse systems, while mainly focusing on the problem of social-ecological fit alongside a scattering of other topics. There is strong potential, however, to engage other issues central to human-environment studies. Analyzing the simultaneous effects of multiple social, environmental, and coupled processes, change over time, and linking network structures to outcomes are also areas for future advancement. This review provides a comprehensive assessment of (fully articulated) SEN research, a necessary step that can help scholars develop comparable cases and fill research gaps.
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| 10. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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