| 1. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 2. |
- Guasconi, Daniela, 1992-
(författare)
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The hidden half of the meadow : Interactions between drought, soil carbon, roots and soil microbial communities
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Soil is a hidden ecosystem which harbours plant roots and countless microorganisms, vital for sustaining life aboveground. These belowground communities provide essential ecosystem services like soil stabilisation and organic matter decomposition. Soil is also one of the largest terrestrial carbon repositories, and land management strategies aimed at increasing organic matter inputs from plants, such as compost additions, can promote further soil carbon accumulation. Because organic carbon is important for soil water retention, this management may also help to increase resilience against more frequent and intense droughts. Although roots and microbial communities are largely acknowledged to play a key role in regulating the carbon cycle, there are still many open questions regarding the link between above- and belowground processes and ecosystem functions. Observing climate- and management-driven changes in the soil habitat is fundamental for understanding how ecosystems respond to environmental change.The aim of this thesis is to explore the relationship between soil properties, plant communities, and soil microbial communities in response to environmental changes. The research builds on a meta-analysis of drought effects on grasslands, and a multifactorial field experiment which combined three years of precipitation reduction and a compost treatment in two Swedish grasslands. We analysed the response of roots and soil microbial communities to drought and compost amendments, and identified environmental factors behind their large spatial variability. Finally, we tested the effects of compost additions on soil carbon storage and its interactions with drought.The results of the meta-analysis indicate that, on a global scale, grassland roots and shoots have diverging responses to drought duration and intensity, with long-term climate mediating that difference. At the local scale assessed in the field experiment, we observed that the spatial patterns of soil microbial communities were driven by soil properties and vegetation. Growing season drought affected roots only at trait level, but did not significantly affect microbial communities. Positive effects of compost on aboveground plant productivity and fungal growth were detectable after three years. Compost amendments also increased the percentage of total soil carbon, but no net increase in soil carbon stocks was detected. Spatial variability in roots and microbial communities was larger than the treatment effects, and was important in shaping microbial community composition and determining grassland responses to drought.Taken together, these findings suggest that roots and microbial communities are likely to be tolerant to drought a within the timescale of this experiment, but we did not observe an increase soil carbon sequestration or drought resilience when adding compost. This thesis highlights the importance of considering soil processes as complementary to aboveground observations when studying carbon dynamics, predicting ecosystem responses to environmental change, and developing sustainable land management practices.
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| 3. |
- Iglesias, Maria Jesus, et al.
(författare)
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Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
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| 4. |
- Dehasque, Marianne, 1993-
(författare)
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Palaeogenomic reconstruction of woolly mammoth evolutionary history and extinction dynamics
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biodiversity is declining globally. Yet, the biological and genetic processes associated with these declines on a longer timescale are still poorly understood. Ancient DNA is a powerful tool to study evolution in real-time. Despite advances in the field, there is further need for refinement of laboratory and computational techniques. In this thesis, I used mitochondrial and nuclear genomes, as well as radiocarbon data, to study the evolutionary history and extinction dynamics of the woolly mammoth (Mammuthus primigenius). In Chapter I, I developed and optimized a silica column-based extraction protocol for ancient DNA. Based on systematic tests, I advise against routine use of pretreatment methods, like bleach wash and/or predigestion, for well-preserved permafrost samples. Furthermore, I suggest that USER enzyme, which removes uracil from damaged DNA molecules, is effective at half the concentration compared to an established control protocol. Finally, I did not find a significant difference between different silica columns for the clean-up steps, or concentrator columns with different DNA retention sizes. In Chapter II, I used five high coverage Siberian mammoth genomes to develop a method based on differences in read depth to identify indels, insertions and deletions, in the mammoth genome. The results show that indels are enriched in intergenic regions, suggesting strong selection against structural variants affecting gene function. Nevertheless, 87 genes were identified that were severely affected. These genes are related to various functions like body-fat distribution, fur growth and hair shape, body temperature, and body size, and most likely represent important adaptations to the cold steppe-tundra. In Chapter III, I studied the population and extinction dynamics of the woolly mammoths in Siberia by combining Bayesian age models from radiocarbon data with inferences from complete mitogenomes. The results show that the woolly mammoth’s extinction was a complex process with consecutive extirpations, but also partial recolonizations, occurring in different Siberian localities. I hypothesize that Wrangel Island, one of the last refugia of the woolly mammoth, was colonized by mammoths from, or closely related to, a population from central or western Siberia. Mammoths reappeared on the island around 10 ky ago, where they became isolated due to rising sea levels, and went extinct around 4 ky ago. To investigate the genetic consequences of the founder bottleneck event of Wrangel Island and long-term survival at small population size, I analyzed time-series data of 21 woolly mammoth genomes in Chapter IV. Changes in heterozygosity and inbreeding show that while the initial bottleneck was dramatic, the population recovered fast and remained remarkably stable. Analysis of mutation load shows that mammoths purged highly deleterious mutations over time, but also accumulated slightly deleterious mutations, indicating reduced efficacy of selection. Nevertheless, there were no clear signs of a mutational meltdown, and it remains a mystery why mammoths went extinct on the island. In conclusion, this thesis presents methodological advances for DNA extraction and detecting structural variants (i.e., deletions) in ancient genomes. Furthermore, I demonstrate that extinctions are a complex process. Finally, I show that ancient DNA is a powerful tool to study evolutionary processes over long timescales.
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| 5. |
- Blake, Vic, et al.
(författare)
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Collective memory work with older men : Ageing, gender politics and masculinities
- 2021. - 1
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Ingår i: Reader Collective Memory-Work. - Sligo : Beltra Books. - 9780992827144 ; , s. 327-353
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Bokkapitel (refereegranskat)abstract
- Over a thirteen-year period, between 2002 and 2015, we were part of what we now call the Older Men’s Memory Work Group (hereafter the group). During our final three years together, we also collaboratively produced and edited a collective book, Men’s Stories for a Change: Ageing Men Remember (Barber et al., 2016; also Blake et al., 2016, 2018) – though it should be said, at the outset, that this was not at all part of our agenda until late in the initial process.Memory work is work on memories, usually though not necessarily collective, and usually also focused on and about some agreed issue(s) of concern. In our case, these memories were about the making and unmaking of older men and masculinities through age, ageing, gender, gendering, and other intersections. Indeed, from the very beginning the group was part of a personal-political project of changing older men and masculinities against patriarchal and sexist ways and relations, and towards feminist and profeminist ways and relations. Here, in this contribution, we first describe the practicalities and the process of our memory work before placing the method itself in its broader framework, and considering its potential for working with older people, and specifically with older men, and with certain implications for practice.
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| 6. |
- Johnson, Linda S, et al.
(författare)
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Markers of Atrial Myopathy in the General Population Prevalence, Predictors, and Inter-Relations
- 2023
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Ingår i: JACC. - : Elsevier. - 2405-500X .- 2405-5018. ; 9:11, s. 2240-2249
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Tidskriftsartikel (refereegranskat)abstract
- Background Atrial myopathy refers to structural and functional cardiac abnormalities associated with atrial fibrillation and stroke, but appropriate diagnostic criteria are lacking.Objectives This study aimed to assess prevalence, clinical correlates, and overlap between potential atrial myopathy markers.Methods The population-based SCAPIS (Swedish CArdioPulmonary bioImage Study) prospectively included 6,013 subjects without atrial fibrillation with 24-hour electrocardiograms. Resting electrocardiograms measuring P-wave indices were collected at 1 screening site (n = 1,201), and a random sample (n = 385) had echocardiographic left atrial volume index (LAVi). Atrial myopathy markers were defined as >= 500 premature atrial complexes/24 h, LAVi >= 34 mL/m(2), P-wave duration >120 milliseconds, or P-wave terminal force in V-1 >4,000 mss. Clinical correlates included age, sex, body mass index, height, smoking, physical activity, coronary artery disease, diabetes, systolic blood pressure, antihypertensive medication, and low education.Results Atrial myopathy was common; 42% of the sample with all diagnostic modalities available had >= 1 atrial myopathy marker, but only 9% had 2 and 0.3% had >= 3. Only P-wave duration and LAVi were correlated (rho = 0.10; P = 0.04). Clinical correlates of premature atrial complexes, P-wave indices, and LAVi differed; current smoking (34% increase; P < 0.001), systolic blood pressure (4%/mm Hg increase; P = 0.01), diabetes (35% increase; P = 0.001), and coronary artery disease (71% increase; P = 0.003) were associated with premature atrial complexes, physical activity >= 2 h/wk was associated with increased LAVi (beta-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (beta-coefficient = 0.4/kg/m(2); P < 0.0001).Conclusions In the general population, indirect markers of atrial myopathy are common but only weakly correlated, and their risk factor patterns are different. More studies are needed to accurately identify individuals with atrial myopathy with diagnostic methods.
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| 7. |
- Moreno, Pablo, et al.
(författare)
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Galaxy-Kubernetes integration: scaling bioinformatics workflows in the cloud
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Making reproducible, auditable and scalable data-processing analysis workflows is an important challenge in the field of bioinformatics. Recently, software containers and cloud computing introduced a novel solution to address these challenges. They simplify software installation, management and reproducibility by packaging tools and their dependencies. In this work we implemented a cloud provider agnostic and scalable container orchestration setup for the popular Galaxy workflow environment. This solution enables Galaxy to run on and offload jobs to most cloud providers (e.g. Amazon Web Services, Google Cloud or OpenStack, among others) through the Kubernetes container orchestrator.
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| 8. |
- Sennefelt Nyman, Sofi, et al.
(författare)
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Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study : idarubicin dose selection, tissue response and survival
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31.
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| 9. |
- Svensson, Robert, et al.
(författare)
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For Whom Do Unstructured Activities Matters? The Interaction Between Unstructured and Structured Activities in Delinquency and Cannabis Use : A National Self-Report Study
- 2023
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Ingår i: Crime and delinquency. - : Sage Publications. - 0011-1287 .- 1552-387X. ; 69:10, s. 2022-2045
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Tidskriftsartikel (refereegranskat)abstract
- This study examines whether unstructured and structured activities interact in their association with delinquency and cannabis use. We hypothesize that unstructured activities are more strongly associated with delinquency and cannabis use for those who are less engaged in structured activities. Data are drawn from three nationally representative self-report studies conducted between 2005 and 2011 in Sweden, and include 19,644 adolescents. The results support the hypothesis that unstructured activities interact with structured activities in the association with delinquency and cannabis use. The association between unstructured activities and these outcomes is stronger for those with lower levels of structured activities. Sporting activities constitute the structured activity that most clearly interacts with unstructured activities in the association with delinquency and cannabis use.
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