| 1. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 2. |
- Halme, P., et al.
(författare)
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Challenges of ecological restoration : Lessons from forests in northern Europe
- 2013
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 167, s. 248-256
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Forskningsöversikt (refereegranskat)abstract
- The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many ecosystem services remain at high level. However, extensive areas of northern forests are heavily exploited and have lost a major part of their biodiversity value. There is a strong requirement to restore these areas towards a more natural condition in order to meet the targets of the Convention on Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here we introduce northern forests as an ecosystem, discuss the historical and recent human impact and provide a brief status report on the ecological restoration projects and research already conducted there. Based on this discussion, we argue that before any restoration actions commence, the ecology of the target ecosystem should be established with the need for restoration carefully assessed and the outcome properly monitored. Finally, we identify the most important challenges that need to be solved in order to carry out efficient restoration with powerful and long-term positive impacts on biodiversity: coping with unpredictability, maintaining connectivity in time and space, assessment of functionality, management of conflicting interests and social restrictions and ensuring adequate funding. © 2013 Elsevier Ltd.
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| 3. |
- Lundtoft, Christian, et al.
(författare)
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Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
- 2022
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:11, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Objective Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjogren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results Heterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 x 10(-9)) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti-Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Conclusion We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
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| 4. |
- Austin, Åsa N., et al.
(författare)
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Synergistic Effects of Rooted Aquatic Vegetation and Drift Wrack on Ecosystem Multifunctionality
- 2021
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Ingår i: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 24:7, s. 1670-1686
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystem multifunctionality is an increasingly popular concept used to approximate multifaceted ecosystem functioning, which in turn may help advance ecosystem-based management. However, while experimental studies have shown a positive effect of diversity on multifunctionality, observational studies from natural systems-particularly aquatic-are scarce. Here, we tested the relative importance of species richness and cover of rooted aquatic vegetation, as well as cover of the loose-lying form of the macroalgae bladderwrack (Fucus vesiculosus), for ecosystem multifunctionality in shallow bays along the western Baltic Sea coast. We estimated multifunctionality based on four indicators of functions that support ecosystem services: recruitment of large predatory fish, grazer biomass, inverted 'nuisance' algal biomass, and water clarity. Piecewise path analysis showed that multifunctionality was driven by high cover of rooted aquatic vegetation and bladderwrack, particularly when the two co-occurred. This synergistic effect was nearly three times as strong as a negative effect of land-derived nitrogen loading. Species richness of aquatic vegetation indirectly benefitted multifunctionality by increasing vegetation cover. Meanwhile, high bladderwrack cover tended to decrease vegetation species richness, indicating that bladderwrack has both positive and negative effects on multifunctionality. We conclude that managing for dense and diverse vegetation assemblages may mitigate effects of anthropogenic pressures (for example, eutrophication) and support healthy coastal ecosystems that provide a range of benefits. To balance the exploitation of coastal ecosystems and maintain their multiple processes and services, management therefore needs to go beyond estimation of vegetation cover and consider the diversity and functional types of aquatic vegetation.
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| 5. |
- De Frenne, Pieter, et al.
(författare)
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Microclimate moderates plant responses to macroclimate warming
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:46, s. 18561-18565
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Tidskriftsartikel (refereegranskat)abstract
- Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., thermophilization of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that climatic lags may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity.
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| 6. |
- 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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| 10. |
- Nordmark, Gunnel, et al.
(författare)
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Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome
- 2011
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:2, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
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