| 1. |
- Kowal-Bielecka, Otylia, et al.
(author)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Journal article (peer-reviewed)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 2. |
- Monroe, J. Grey, et al.
(author)
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Mutation bias reflects natural selection in Arabidopsis thaliana
- 2022
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 602:7895, s. 101-105
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Journal article (peer-reviewed)abstract
- Since the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences(1). Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome-mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution.
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| 3. |
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| 4. |
- Riba, Miquel, et al.
(author)
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Darwin's wind hypothesis : does it work for plant dispersal in fragmented habitats?
- 2009
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In: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 183:3, s. 667-677
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Journal article (peer-reviewed)abstract
- Using the wind-dispersed plant Mycelis muralis, we examined how landscape fragmentation affects variation in seed traits contributing to dispersal. Inverse terminal velocity () of field-collected achenes was used as a proxy for individual seed dispersal ability. We related this measure to different metrics of landscape connectivity, at two spatial scales: in a detailed analysis of eight landscapes in Spain and along a latitudinal gradient using 29 landscapes across three European regions. In the highly patchy Spanish landscapes, seed increased significantly with increasing connectivity. A common garden experiment suggested that differences in may be in part genetically based. The was also found to increase with landscape occupancy, a coarser measure of connectivity, on a much broader (European) scale. Finally, was found to increase along a south2013north latitudinal gradient. Our results for M. muralis are consistent with 'Darwin's wind dispersal hypothesis' that high cost of dispersal may select for lower dispersal ability in fragmented landscapes, as well as with the 'leading edge hypothesis' that most recently colonized populations harbour more dispersive phenotypes.
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| 5. |
- Weng, Mao-Lun, et al.
(author)
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Fitness effects of mutation in natural populations of Arabidopsis thaliana reveal a complex influence of local adaptation
- 2021
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In: Evolution. - : John Wiley & Sons. - 0014-3820 .- 1558-5646. ; 75:2, s. 330-348
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Journal article (peer-reviewed)abstract
- Little is empirically known about the contribution of mutations to fitness in natural environments. However, Fisher's Geometric Model (FGM) provides a conceptual foundation to consider the influence of the environment on mutational effects. To quantify mutational properties in the field, we established eight sets of MA lines (7-10 generations) derived from eight founders collected from natural populations of Arabidopsis thaliana from French and Swedish sites, representing the range margins of the species in Europe. We reciprocally planted the MA lines and their founders at French and Swedish sites, allowing us to test predictions of FGM under naturally occurring environmental conditions. The performance of the MA lines relative to each other and to their respective founders confirmed some and contradicted other predictions of the FGM: the contribution of mutation to fitness variance increased when the genotype was in an environment where its fitness was low, that is, in the away environment, but mutations were more likely to be beneficial when the genotype was in its home environment. Consequently, environmental context plays a large role in the contribution of mutations to the evolutionary process and local adaptation does not guarantee that a genotype is at or close to its optimum.
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