| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 3. |
- Consonni, A., et al.
(författare)
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A Novel Approach to Reinstating Tolerance in Experimental Autoimmune Myasthenia Gravis Using Targeted Fusion Protein, mCTA1-T146
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required. Hence, there is a need for better formulations and strategies to improve on the efficacy of the tolerance-inducing therapies. Here, we report on a novel targeted fusion protein carrying the immunodominant peptide from AChR, mCTA1-T146, which given intranasally in repeated microgram doses strongly suppressed induction as well as ongoing EAMG disease in mice. The results corroborate our previous findings, using the same fusion protein approach, in the collagen-induced arthritis model showing dramatic suppressive effects on Th1 and Th17 autoaggressive CD4 T cells and upregulated regulatory T cell activities with enhanced IL10 production. A suppressive gene signature with upregulated expression of mRNA for TGF beta, IL10, IL27, and Foxp3 was clearly detectable in lymph node and spleen following intranasal treatment with mCTA1-T146. Amelioration of EAMG disease was accompanied by reduced loss of muscle AChR and lower levels of anti-AChR serum antibodies. We believe this targeted highly effective fusion protein mCTA1-T146 is a promising candidate for clinical evaluation in myasthenia gravis patients.
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| 4. |
- Dawed, Adem Y., et al.
(författare)
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Pharmacogenomics of GLP-1 receptor agonists : a genome- wide analysis of observational data and large randomised controlled trials
- 2023
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 11:1, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods:In this genome-wide analysis we included adults (aged & GE;18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings:4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G & RARR;A (Gly168Ser) in the GLP1R (0.08% [95% CI 0.04-0.12] or 0.9 mmol/mol lower reduction in HbA1c per serine, p=6.0 x 10-5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6.7 x 10-8), largely driven by rs140226575G & RARR;A (Thr370Met; 0.25% [SE 0.06] or 2.7 mmol/mol [SE 0.7] greater HbA1c reduction per methionine, p=5.2 x 10-6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6-11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation:This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists.
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| 5. |
- Eriksen, Rebeca, et al.
(författare)
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Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.
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| 6. |
- Frassl, Marieke A., et al.
(författare)
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Ten simple rules for collaboratively writing a multi-authored paper
- 2018
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Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 14:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Science is increasingly done in large teams, making it more likely that papers will be written by several authors from different institutes, disciplines, and cultural backgrounds. A small number of “Ten simple rules” papers have been written on collaboration and on writing but not on combining the two. Collaborative writing with multiple authors has additional challenges, including varied levels of engagement of coauthors, provision of fair credit through authorship or acknowledgements, acceptance of a diversity of work styles, and the need for clear communication. Miscommunication, a lack of leadership, and inappropriate tools or writing approaches can lead to frustration, delay of publication, or even the termination of a project.To provide insight into collaborative writing, we use our experience from the Global Lake Ecological Observatory Network (GLEON) to frame 10 simple rules for collaboratively writing a multi-authored paper. We consider a collaborative multi-authored paper to have three or more people from at least two different institutions. A multi-authored paper can be a result of a single discrete research project or the outcome of a larger research program that includes other papers based on common data or methods. The writing of a multi-authored paper is embedded within a broader context of planning and collaboration among team members. Our recommended rules include elements of both the planning and writing of a paper, and they can be iterative, although we have listed them in numerical order. It will help to revisit the rules frequently throughout the writing process. With the 10 rules outlined below, we aim to provide a foundation for writing multi-authored papers and conducting exciting and influential science.
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| 7. |
- Frkatović-Hodžić, Azra, et al.
(författare)
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Mapping of the gene network that regulates glycan clock of ageing
- 2023
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Ingår i: Aging. - 1945-4589. ; 15:24, s. 14509-14552
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Tidskriftsartikel (refereegranskat)abstract
- Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.
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| 8. |
- Gudmundsdottir, Valborg, et al.
(författare)
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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study
- 2020
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.Conclusions: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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| 9. |
- Hampton, Stephanie E., et al.
(författare)
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Ecology under lake ice
- 2017
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111
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Forskningsöversikt (refereegranskat)abstract
- Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
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| 10. |
- Jansen, Joachim, 1989-, et al.
(författare)
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Global increase in methane production under future warming of lake bottom waters
- 2022
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 28:18, s. 5427-5440
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Tidskriftsartikel (refereegranskat)abstract
- Lakes are significant emitters of methane to the atmosphere, and thus are important components of the global methane budget. Methane is typically produced in lake sediments, with the rate of methane production being strongly temperature dependent. Local and regional studies highlight the risk of increasing methane production under future climate change, but a global estimate is not currently available. Here, we project changes in global lake bottom temperatures and sediment methane production rates from 1901 to 2099. By the end of the 21st century, lake bottom temperatures are projected to increase globally, by an average of 0.86-2.60 degrees C under Representative Concentration Pathways (RCPs) 2.6-8.5, with greater warming projected at lower latitudes. This future warming of bottom waters will likely result in an increase in methane production rates of 13%-40% by the end of the century, with many low-latitude lakes experiencing an increase of up to 17 times the historical (1970-1999) global average under RCP 8.5. The projected increase in methane production will likely lead to higher emissions from lakes, although the exact magnitude of the emission increase requires more detailed regional studies.
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| 11. |
- Jenny, Jean Philippe, et al.
(författare)
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Scientists’ Warning to Humanity: Rapid degradation of the world's large lakes
- 2020
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Ingår i: Journal of Great Lakes Research. - : Elsevier BV. - 0380-1330. ; 46:4, s. 686-702
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Forskningsöversikt (refereegranskat)abstract
- © 2020 The Authors Large lakes of the world are habitats for diverse species, including endemic taxa, and are valuable resources that provide humanity with many ecosystem services. They are also sentinels of global and local change, and recent studies in limnology and paleolimnology have demonstrated disturbing evidence of their collective degradation in terms of depletion of resources (water and food), rapid warming and loss of ice, destruction of habitats and ecosystems, loss of species, and accelerating pollution. Large lakes are particularly exposed to anthropogenic and climatic stressors. The Second Warning to Humanity provides a framework to assess the dangers now threatening the world's large lake ecosystems and to evaluate pathways of sustainable development that are more respectful of their ongoing provision of services. Here we review current and emerging threats to the large lakes of the world, including iconic examples of lake management failures and successes, from which we identify priorities and approaches for future conservation efforts. The review underscores the extent of lake resource degradation, which is a result of cumulative perturbation through time by long-term human impacts combined with other emerging stressors. Decades of degradation of large lakes have resulted in major challenges for restoration and management and a legacy of ecological and economic costs for future generations. Large lakes will require more intense conservation efforts in a warmer, increasingly populated world to achieve sustainable, high-quality waters. This Warning to Humanity is also an opportunity to highlight the value of a long-term lake observatory network to monitor and report on environmental changes in large lake ecosystems.
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| 12. |
- Knoll, Lesley B., et al.
(författare)
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Consequences of lake and river ice loss on cultural ecosystem services
- 2019
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Ingår i: Limnology and Oceanography Letters. - : Wiley Periodicals Inc.. - 2378-2242. ; 4:5, s. 119-131
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Tidskriftsartikel (refereegranskat)abstract
- People extensively use lakes and rivers covered by seasonal ice. Although ice cover duration has been declining over the past 150 years for Northern Hemisphere freshwaters, we know relatively little about how ice loss directly affects humans. Here, we synthesize the cultural ecosystem services (i.e., services that provide intangible or nonmaterial benefits) and associated benefits supported by inland ice. We also provide, for the first time, empirical examples that give quantitative evidence for a winter warming effect on a wide range of ice-related cultural ecosystem services and benefits. We show that in recent decades, warmer air temperatures delayed the opening date of winter ice roads and led to cancellations of spiritual ceremonies, outdoor ice skating races, and ice fishing tournaments. Additionally, our synthesis effort suggests unexploited data sets that allow for the use of integrative approaches to evaluate the interplay between inland ice loss and society.
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| 13. |
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| 14. |
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| 15. |
- O’Reilly, Catherine M., et al.
(författare)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Tidskriftsartikel (refereegranskat)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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| 16. |
- Reinl, Kaitlin L., et al.
(författare)
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Blooms also like it cold
- 2023
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Ingår i: Limnology and Oceanography Letters. - : John Wiley & Sons. - 2378-2242. ; 8:4, s. 546-564
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Forskningsöversikt (refereegranskat)abstract
- Cyanobacterial blooms have substantial direct and indirect negative impacts on freshwater ecosystems including releasing toxins, blocking light needed by other organisms, and depleting oxygen. There is growing concern over the potential for climate change to promote cyanobacterial blooms, as the positive effects of increasing lake surface temperature on cyanobacterial growth are well documented in the literature; however, there is increasing evidence that cyanobacterial blooms are also being initiated and persisting in relatively cold-water temperatures (< 15 °C), including ice-covered conditions. In this work, we provide evidence of freshwater cold-water cyanobacterial blooms, review abiotic drivers and physiological adaptations leading to these blooms, offer a typology of these lesser-studied cold-water cyanobacterial blooms, and discuss their occurrence under changing climate conditions.
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| 17. |
- Richardson, David C., et al.
(författare)
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Nonlinear responses in interannual variability of lake ice to climate change
- 2024
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Ingår i: Limnology and Oceanography. - : Association for the Sciences of Limnology and Oceanography. - 0024-3590 .- 1939-5590. ; 69:4, s. 789-801
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is contributing to rapid changes in lake ice cover across the Northern Hemisphere, thereby impacting local communities and ecosystems. Using lake ice cover time-series spanning over 87 yr for 43 lakes across the Northern Hemisphere, we found that the interannual variability in ice duration, measured as standard deviation, significantly increased in only half of our studied lakes. We observed that the interannual variability in ice duration peaked when lakes were, on average, covered by ice for about 1 month, while both longer and shorter long-term mean ice cover duration resulted in lower interannual variability in ice duration. These results demonstrate that the ice cover duration can become so short that the interannual variability rapidly declines. The interannual variability in ice duration showed a strong dependency on global temperature anomalies and teleconnections, such as the North Atlantic Oscillation and El Nino-Southern Oscillation. We conclude that many lakes across the Northern Hemisphere will experience a decline in interannual ice cover variability and shift to open water during the winter under a continued global warming trend which will affect lake biological, cultural, and economic processes.
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| 18. |
- Sharma, Sapna, et al.
(författare)
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A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
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Ingår i: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
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| 19. |
- Sharma, Sapna, et al.
(författare)
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A Sensitive Method for Detecting Peptide-specific CD4(+) T Cell Responses in Peripheral Blood from Patients with Myasthenia Gravis
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Myasthenia gravis (MG) is an autoimmune neurological disorder typified by skeletal muscle fatigue and most often production of autoantibodies against the nicotinic acetylcholine receptor (AChR). The present study was undertaken to assess the extent of AChR-peptide recognition in MG patients using co-culturing (DC:TC) of autologous monocyte-derived dendritic cells (moDCs) and highly enriched CD4(+) T cells from the blood as compared to the traditional whole peripheral blood mononuclear cell (PBMC) cultures. We found that the DC:TC cultures were highly superior to the PBMC cultures for detection of reactivity toward HLA-DQ/DR-restricted AChR-peptides. In fact, whereas DC:TC cultures identified recognition in all MG patients the PBMC cultures failed to detect responsiveness in around 40% of the patients. Furthermore, reactivity to multiple peptides was evident in DC:TC cultures, while PBMC cultures mostly exhibited reactivity to a single peptide. No healthy control (HC) CD4(+) T cells responded to the peptides in either culture system. Interestingly, whereas spontaneous production of IFN. and IL-17 was observed in the DC:TC cultures from MG patients, recall responses to peptides enhanced IL-10 production in 9/13 MG patients, while little increase in IFN. and IL-17 was seen. HCs did not produce cytokines to peptide stimulations. We conclude that the DC:TC culture system is significantly more sensitive and better identifies the extent of responsiveness in MG patients to AChR-peptides than traditional PBMC cultures.
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| 20. |
- Sharma, Sapna, et al.
(författare)
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Increased winter drownings in ice-covered regions with warmer winters
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Winter activities on ice are culturally important for many countries, yet they constitute a high safety risk depending upon the stability of the ice. Because consistently cold periods are required to form stable and thick ice, warmer winters could degrade ice conditions and increase the likelihood of falling through the ice. This study provides the first large-scale assessment of winter drowning from 10 Northern Hemisphere countries. We documented over 4000 winter drowning events. Winter drownings increased exponentially in regions with warmer winters when air temperatures neared 0 degrees C. The largest number of drownings occurred when winter air temperatures were between -5 degrees C and 0 degrees C, when ice is less stable, and also in regions where indigenous traditions and livelihood require extended time on ice. Rates of drowning were greatest late in the winter season when ice stability declines. Children and adults up to the age of 39 were at the highest risk of winter drownings. Beyond temperature, differences in cultures, regulations, and human behaviours can be important additional risk factors. Our findings indicate the potential for increased human mortality with warmer winter air temperatures. Incorporating drowning prevention plans would improve adaptation strategies to a changing climate.
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| 21. |
- Sharma, Sapna, et al.
(författare)
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Long-term ice phenology records spanning up to 578 years for 78 lakes around the Northern Hemisphere
- 2022
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- In recent decades, lakes have experienced unprecedented ice loss with widespread ramifications for winter ecological processes. The rapid loss of ice, resurgence of winter biology, and proliferation of remote sensing technologies, presents a unique opportunity to integrate disciplines to further understand the broad spatial and temporal patterns in ice loss and its consequences. Here, we summarize ice phenology records for 78 lakes in 12 countries across North America, Europe, and Asia to permit the inclusion and harmonization of in situ ice phenology observations in future interdisciplinary studies. These ice records represent some of the longest climate observations directly collected by people. We highlight the importance of applying the same definition of ice-on and ice-off within a lake across the time-series, regardless of how the ice is observed, to broaden our understanding of ice loss across vast spatial and temporal scales.
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| 22. |
- Sharma, Sapna, et al.
(författare)
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Loss of Ice Cover, Shifting Phenology, and More Extreme Events in Northern Hemisphere Lakes
- 2021
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 126:10
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Tidskriftsartikel (refereegranskat)abstract
- Long-term lake ice phenological records from around the Northern Hemisphere provide unique sensitive indicators of climatic variations, even prior to the existence of physical meteorological measurement stations. Here, we updated ice phenology records for 60 lakes with time-series ranging from 107-204 years to provide the first re-assessment of Northern Hemispheric ice trends since 2004 by adding 15 additional years of ice phenology records and 40 lakes to our study. We found that, on average, ice-on was 11.0 days later, ice-off was 6.8 days earlier, and ice duration was 17.0 days shorter per century over the entire record for each lake. Trends in ice-on and ice duration were six times faster in the last 25-year period (1992-2016) than previous quarter centuries. More extreme events in recent decades, including late ice-on, early ice-off, shorter periods of ice cover, or no ice cover at all, contribute to the increasing rate of lake ice loss. Reductions in greenhouse gas emissions could limit increases in air temperature and abate losses in lake ice cover that would subsequently limit ecological, cultural, and socioeconomic consequences, such as increased evaporation rates, warmer water temperatures, degraded water quality, and the formation of toxic algal blooms.
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| 23. |
- Sharma, Sapna, et al.
(författare)
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Widespread loss of lake ice around the Northern Hemisphere in a warming world
- 2019
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Ingår i: Nature Climate Change. - : NATURE PUBLISHING GROUP. - 1758-678X .- 1758-6798. ; 9:3, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Ice provides a range of ecosystem services-including fish harvest(1), cultural traditions(2), transportation(3), recreation(4) and regulation of the hydrological cycle(5)-to more than half of the world's 117 million lakes. One of the earliest observed impacts of climatic warming has been the loss of freshwater ice(6), with corresponding climatic and ecological consequences(7). However, while trends in ice cover phenology have been widely documented(2,6,8,9), a comprehensive large-scale assessment of lake ice loss is absent. Here, using observations from 513 lakes around the Northern Hemisphere, we identify lakes vulnerable to ice-free winters. Our analyses reveal the importance of air temperature, lake depth, elevation and shoreline complexity in governing ice cover. We estimate that 14,800 lakes currently experience intermittent winter ice cover, increasing to 35,300 and 230,400 at 2 and 8 degrees C, respectively, and impacting up to 394 and 656 million people. Our study illustrates that an extensive loss of lake ice will occur within the next generation, stressing the importance of climate mitigation strategies to preserve ecosystem structure and function, as well as local winter cultural heritage.
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| 24. |
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| 25. |
- Weyhenmeyer, Gesa A., Professor, et al.
(författare)
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Global Lake Health in the Anthropocene : Societal Implications and Treatment Strategies
- 2024
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Ingår i: Earth's Future. - : American Geophysical Union (AGU). - 2328-4277. ; 12:4
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Forskningsöversikt (refereegranskat)abstract
- The world's 1.4 million lakes (>= 10 ha) provide many ecosystem services that are essential for human well-being; however, only if their health status is good. Here, we reviewed common lake health issues and classified them using a simple human health-based approach to outline that lakes are living systems that are in need of oxygen, clean water and a balanced energy and nutrient supply. The main reason for adopting some of the human health terminology for the lake health classification is to increase the awareness and understanding of global lake health issues. We show that lakes are exposed to various anthropogenic stressors which can result in many lake health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Of particular concern for human well-being is the widespread lake drying, which is a severe circulatory issue with many cascading effects on lake health. We estimated that similar to 115,000 lakes evaporate twice as much water as they gain from direct precipitation, making them vulnerable to potential drying if inflowing waters follow the drying trend, putting more than 153 million people at risk who live in close vicinity to those lakes. Where lake health issues remain untreated, essential ecosystem services will decline or even vanish, posing a threat to the well-being of millions of people. We recommend coordinated multisectoral and multidisciplinary prevention and treatment strategies, which need to include a follow-up of the progress and an assessment of the resilience of lakes to intensifying threats. Priority should be given to implementing sewage water treatment, mitigating climate change, counteracting introductions of non-native species to lakes and decreasing uncontrolled anthropogenic releases of chemicals into the hydro-, bio-, and atmosphere. Lakes around the world come in an array of sizes, shapes and colors, each telling a unique story of geological history and environmental importance. When lakes are healthy they contribute to the achievement of the global sustainable development goals by providing many important ecosystem services. Lakes are, however, not always healthy. Here, it is shown that lakes can suffer from a large variety of health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Without improved treatment strategies, many of the health issues may become chronic, affecting millions of people who are dependent on the ecosystem services from the lakes. To prevent and cure lakes from critical health conditions, strategies that are similar to those used in human healthcare should be applied: intervention and preventative actions before health problems occur, regular screening and early identification of lake health issues, and remediation and mitigation efforts at an appropriate scale, spanning from local to global. Anthropogenic stressors can cause lake health issues that range from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning Lake health varies geographically, with the highest risk of critical conditions occurring in densely populated low-income countries There is an urgent need to follow-up the progress of treatments and to make adjustments whenever needed
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