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| 10. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 14. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 15. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 16. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 17. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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- Rader, Romina, et al.
(författare)
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Non-bee insects are important contributors to global crop pollination.
- 2016
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 113:1, s. 146-151
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Tidskriftsartikel (refereegranskat)abstract
- Wild and managed bees are well documented as effective pollinators of global crops of economic importance. However, the contributions by pollinators other than bees have been little explored despite their potential to contribute to crop production and stability in the face of environmental change. Non-bee pollinators include flies, beetles, moths, butterflies, wasps, ants, birds, and bats, among others. Here we focus on non-bee insects and synthesize 39 field studies from five continents that directly measured the crop pollination services provided by non-bees, honey bees, and other bees to compare the relative contributions of these taxa. Non-bees performed 25-50% of the total number of flower visits. Although non-bees were less effective pollinators than bees per flower visit, they made more visits; thus these two factors compensated for each other, resulting in pollination services rendered by non-bees that were similar to those provided by bees. In the subset of studies that measured fruit set, fruit set increased with non-bee insect visits independently of bee visitation rates, indicating that non-bee insects provide a unique benefit that is not provided by bees. We also show that non-bee insects are not as reliant as bees on the presence of remnant natural or seminatural habitat in the surrounding landscape. These results strongly suggest that non-bee insect pollinators play a significant role in global crop production and respond differently than bees to landscape structure, probably making their crop pollination services more robust to changes in land use. Non-bee insects provide a valuable service and provide potential insurance against bee population declines.
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| 20. |
- De Palma, Adriana, et al.
(författare)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 21. |
- Goldberg, Emily L., et al.
(författare)
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beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:9, s. 2077-2087
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Tidskriftsartikel (refereegranskat)abstract
- Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1 beta (IL-1 beta) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases beta-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1 beta in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.
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| 22. |
- Herzog, Simon D., et al.
(författare)
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Salinity Effects on Iron Speciation in Boreal River Waters
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:17, s. 9747-9755
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies report high and increasing iron (Fe) concentrations in boreal river mouths. This Fe has shown relatively high stability to salinity-induced aggregation in estuaries. The aim of this study was to understand how the speciation of Fe affects stability over salinity gradients. For Fe to remain in suspension interactions with organic matter (OM) are fundamental and these interactions can be divided in two dominant phases: organically complexed Fe, and colloidal Fe (oxy)hydroxides, stabilized by surface interactions with OM. The stability of these two Fe phases was tested using mixing experiments with river water and artificial seawater. Fe speciation of river waters and salinity-induced aggregates was determined by synchrotron-based extended X-ray absorption fine structure (EXAFS) spectroscopy. The relative contribution of the two Fe phases varied widely across the sampled rivers. Moreover, we found selective removal of Fe (oxy)hydroxides by aggregation at increasing salinity, while organically complexed Fe was less affected. However, Fe-OM complexes were also found in the aggregates, illustrating that the control of Fe stability is not explained by the prevalence of the respective Fe phases alone. Factors such as colloid size and the chemical composition of the OM may also impact the behavior of Fe species.
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| 23. |
- Herzog, S. D., et al.
(författare)
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Spring flood induced shifts in Fe speciation and fate at increased salinity
- 2019
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Ingår i: Applied Geochemistry. - : Elsevier. - 0883-2927 .- 1872-9134. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- Rivers have traditionally been viewed as negligible sources of iron (Fe) to marine waters, as most Fe gets lost during estuarine mixing. However, recent findings demonstrate that Fe from boreal rivers display a higher resistance towards salinity-induced aggregation, presumably due to stabilizing interactions with organic matter. Previous studies have shown that Fe (oxy)hydroxides are selectively removed by aggregation processes, and that organic Fe complexes are less affected by increasing salinity. It has been further proposed that Fe speciation varies in response to seasonal differences in hydrology. In this study X-ray absorption spectroscopy (XAS) was used to determine the temporal variation in Fe speciation and the connection to Fe stability in response to increasing salinity in two boreal rivers (Kalix and Råne River), with the purpose to better understand the fate of riverine Fe export. Sampling was done from winter pre-flood, over the spring flood, to post-flood conditions (early April until mid June). In addition, parallel analyses for Fe speciation and isotope composition (δ56Fe relative to IRMM-14) were made on river samples, as well as salinity-induced aggregates and the fraction remaining in suspension, with the main objective to test if δ56Fe reflect the speciation of Fe.The contribution of organically complexed Fe increased during spring flood compared to the pre- and post-flood, as did Fe transport capacity. However, since Fe (oxy)hydroxides were dominating throughout the sampling period, the seasonal variability was small. Interestingly, salinity-induced aggregation experiments revealed that Fe (oxy)hydroxides, which dominated aggregates, displayed lower δ56Fe than in the river samples Fe, while organic Fe complexes in suspension had higher δ56Fe values. The seasonal variability in Fe isotope signature could not be simply linked to Fe speciation, but was probably also influenced by variation in source areas of Fe and processes along the flow-path that alter both Fe speciation and isotopic composition.
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| 25. |
- Kleijn, David, et al.
(författare)
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Delivery of crop pollination services is an insufficient argument for wild pollinator conservation.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.
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| 26. |
- Lewandowski, Jörg, et al.
(författare)
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Is the Hyporheic Zone Relevant beyond the Scientific Community?
- 2019
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Ingår i: Water. - : MDPI AG. - 2073-4441. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Rivers are important ecosystems under continuous anthropogenic stresses. The hyporheic zone is a ubiquitous, reactive interface between the main channel and its surrounding sediments along the river network. We elaborate on the main physical, biological, and biogeochemical drivers and processes within the hyporheic zone that have been studied by multiple scientific disciplines for almost half a century. These previous efforts have shown that the hyporheic zone is a modulator for most metabolic stream processes and serves as a refuge and habitat for a diverse range of aquatic organisms. It also exerts a major control on river water quality by increasing the contact time with reactive environments, which in turn results in retention and transformation of nutrients, trace organic compounds, fine suspended particles, and microplastics, among others. The paper showcases the critical importance of hyporheic zones, both from a scientific and an applied perspective, and their role in ecosystem services to answer the question of the manuscript title. It identifies major research gaps in our understanding of hyporheic processes. In conclusion, we highlight the potential of hyporheic restoration to efficiently manage and reactivate ecosystem functions and services in river corridors.
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| 28. |
- Nilsson, Sara, 1990-
(författare)
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How requirements development could support design of effective and resource-efficient offerings
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- What a company offers its customers has to fulfil several different needs, desires, constraints, which can originate from multiple different sources that affect the offering throughout its life cycle. All these criteria have to come together and be translated into statements that can support the designer’s understanding of the offering’s purpose. This translation is done through a requirements development process to provide a controlled process to define statements that describe what the offering is supposed to fulfil.This research provides insights on key challenges and success factors in requirements development to support the design of effective and resource-efficient offerings. Namely, it identifies crucial sources and aspects to be considered, and a requirements development process demonstrating how to overcome identified challenges. By getting the requirements right from the beginning, sub-optimisation and unnecessary time and risks can be avoided. The consideration of accurate sources and aspects is considered to be one of the most important factors for the successful design of offerings. It is also in the earliest phases of design, that is to say requirements development, where one has the greatest possibility to affect the environmental impact of the offering. What is missing, however, is sufficient and appropriate support in industry on how to do so.The gap between the three areas of effectiveness and resource efficiency, design of integrated offerings, and requirements development has been investigated. Results are based on findings in the literature and in industry, identified primarily by qualitative studies. In the research, 15 different companies have been included through a number of interviews and discussions.Key sources and aspects to consider in the requirements development process are identified along with challenges, and success factors that can be utilised to overcome the identified challenges. This research’s final results include an adapted requirements development process that considers the earlier-mentioned sources and aspect, challenges, and success factors. Such a requirements development process should support the design of effective and resource-efficient offerings.
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