| 1. |
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| 2. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
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| 4. |
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| 5. |
- Eme, Laura, et al.
(författare)
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Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 992-
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Tidskriftsartikel (refereegranskat)abstract
- In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes(1). However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved(2-4). Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.
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| 6. |
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| 7. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 8. |
- Narrowe, Adrienne B., et al.
(författare)
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Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids
- 2018
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 10:9, s. 2380-2393
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Tidskriftsartikel (refereegranskat)abstract
- Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome. In part due to the role of diphthamide in maintaining translational fidelity, it was previously assumed that diphthamide biosynthesis genes (dph) are conserved across all eukaryotes and archaea. Here, comparative analysis of new and existing genomes reveals that some archaea (i.e., members of the Asgard superphylum, Geoarchaea, and Korarchaeota) and eukaryotes (i.e., parabasalids) lack dph. In addition, while EF-2 was thought to exist as a single copy in archaea, many of these dph-lacking archaeal genomes encode a second EF-2 paralog missing key residues required for diphthamide modification and for normal translocase function, perhaps suggesting functional divergence linked to loss of diphthamide biosynthesis. Interestingly, some Heimdallarchaeota previously suggested to be most closely related to the eukaryotic ancestor maintain dph genes and a single gene encoding canonical EF-2. Our findings reveal that the ability to produce diphthamide, once thought to be a universal feature in archaea and eukaryotes, has been lost multiple times during evolution, and suggest that anticipated compensatory mechanisms evolved independently.
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| 9. |
- Nyberg, Eva, 1958, et al.
(författare)
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Känslor och estetik i förskolans naturvetenskap.
- 2020
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Ingår i: Presentation på den digitala konferensen: FND 2020 "Flerspråkighet och multimodalitet i naturvetenskapernas och teknikens didaktik", 11-12 nov, Svensk förening för forskning i naturvetenskapernas didaktik. Göteborg: Göteborgs universitet..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I ett samarbetsprojekt inom den svenska nationella satsningen på praktiknära skolforskning arbetar lärare på förskola, skola och universitet med att utveckla undervisningen i naturvetenskap och samtidigt barnens förmåga att uttrycka sig på svenska, i en stadsdel med hög grad av multikulturalitet. En målsättning är att projektet skall leda till ämnesdidaktiska modeller att ha som utgångspunkt vid planering, genomförande och utvärdering av verksamheten. Under projektets första år har samarbetet delvis bedrivits i s.k. forskarpar, bestående av lärare från förskolans eller skolans verksamhet och lärare från universitetet. I två av grupperingarna på förskolan har arbetet kommit att handla om att utforska, förstå och lära, genom att uppmuntra och ta sin utgångspunkt i barnens upplevelser, nyfikenhet och skapande. Arbetet har dokumenterats genom gemensamma interaktiva loggböcker. Undervisningspraktiken har länge uppmärksammat betydelsen och värdet av att ”undervisa med alla sinnen” och därför använt multimodala uttrycksformer. I den ämnesdidaktiska forskningen har betydelsen av estetiska upplevelser, som kan innefatta sådant som upplevs som vackert eller trevligt, men också fult eller otrevligt, studerats med avseende på barns intresse för naturvetenskap och för vad de lär sig och förstår. Preliminära analyser av loggböckerna visar att förskolelärarna genomgående arbetar med en mängd olika uttrycksformer med hög grad av estetiska upplevelser och att barnens frågor och nyfikenhet delvis styr hur aktiviteterna utvecklas. I ett tema om jord, utforskar barn och lärare gemensamt daggmaskar. Barnen tycks utveckla omsorg om maskarna och en förståelse för hur människan kan påverka deras livsförutsättningar. Verksamheten under temat innehåller därmed en rad exempel på hur förskolans mål och riktlinjer kan förverkligas under ett och samma tema, liksom rikhaltiga exempel på multimodala uttrycksformer och på ett språkutvecklande arbetssätt. De preliminära resultaten diskuteras med avseende på om aktiviteter med ett fokus på estetiska upplevelser skulle kunna betraktas och användas som en ämnesdidaktisk modell i verksamheter med ett naturvetenskapligt innehåll.
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| 10. |
- Nyberg, Eva, 1958, et al.
(författare)
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Känslor och estetik i förskolans naturvetenskap : Emotions and aesthetics in preschool science
- 2022
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Ingår i: NorDiNa : Nordic Studies in Science Education. - : University of Oslo Library. - 1504-4556 .- 1894-1257. ; 18:2, s. 254-269
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Tidskriftsartikel (refereegranskat)abstract
- The significance of aesthetic experiences, including things perceived as beautiful or pleasant, but also ugly or unpleasant, has been studied in relation to children’s interest and learning in science. The purpose of the present study is to contribute to the development of knowledge about how aesthetics and exploratory approaches are used in preschool teaching in science. Based on this, we wanted to examine the possibility that a focus on aesthetic experiences and experiences based on living organisms or natural objects could be considered and used as a subject didactic model in activities with scientific content. The article is based on an analysis of interactive logbooks from a collaborative project between preschool and university. Our results show that aesthetic experiences and expressions appear as constantly present andin constant change and development in the preschool’s activities, and that this is driven by the children’s and educators’ curiosity and creativity in close interaction. Our conclusion is that a subject didactic model with a focus on aesthetic experiences might contribute to this didactic approach being formulated, concretized and developed in preschool teaching.
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| 11. |
- Oberg, S., et al.
(författare)
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Chronic pain after reoperation of an inguinal hernia with Lichtenstein or laparoscopic repair following a primary Lichtenstein repair: A nationwide questionnaire study
- 2020
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Ingår i: American Journal of Surgery. - : Elsevier BV. - 0002-9610. ; 219:4, s. 701-706
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to assess chronic pain after two Lichtenstein repairs for inguinal hernias (Lichtenstein-Lichtenstein) compared with Lichtenstein followed by a laparoscopic reoperation (Lichtenstein-Laparoscopy). Methods: In this cohort study, adults having an inguinal hernia reoperation were identified in a nationwide database. Lichtenstein-Lichtenstein was matched 1:3 with Lichtenstein-Laparoscopy and sent validated pain questionnaires. The primary outcome was difference in proportion of patients with chronic pain-related functional impairment. Secondary outcomes were differences in chronic pain prevalence and severity. Results: In total, 196 patients having Lichtenstein-Lichtenstein and 777 patients having Lichtenstein-Laparoscopy were included. There was no difference in the primary outcome, 26% with pain in Lichtenstein-Lichtenstein versus 19% in Lichtenstein-Laparoscopy (p = 0.051). However, a few of the secondary outcomes favored Lichtenstein-Laparoscopy. Conclusions: A high proportion of patients in both groups had pain several years after the second repair. None of the analyses favored Lichtenstein-Lichtenstein, but a few of the secondary outcomes favored Lichtenstein-Laparoscopy. (C) 2019 Elsevier Inc. All rights reserved.
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| 12. |
- Peñas-Lledó, Eva, et al.
(författare)
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Risk for self-reported anorexia or bulimia nervosa based on drive for thinness and negative affect clusters/dimensions during adolescence : A three-year prospective study of the TChAD cohort
- 2015
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Ingår i: International Journal of Eating Disorders. - Hoboken, USA : Wiley-Blackwell. - 0276-3478 .- 1098-108X. ; 48:6, s. 692-699
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study explored the cross-sectional and predictive effect of drive for thinness and/or negative affect scores on the development of self-reported anorexia nervosa (AN) and bulimia nervosa (BN).Method: K-means were used to cluster the Eating Disorder Inventory-Drive for Thinness (DT) and Child Behavior Checklist Anxious/Depressed (A/D) scores from 615 unrelated female twins at age 16-17. Logistic regressions were used to assess the effect of these clusters on self-reported eating disorder diagnosis at ages 16-17 (n = 565) and 19-20 (n = 451).Results: DT and A/D scores were grouped into four clusters: Mild (scores lower than 90th percentile on both scales), DT (higher scores only on DT), A/D (higher scores only on A/D), and DT-A/D (higher scores on both the DT and A/D scales). DT and DT-A/D clusters at age 16-17 were associated cross-sectionally with AN and both cross-sectionally and longitudinally with BN. The DT-A/D cluster had the highest prevalence of AN at follow-up compared with all other clusters. Similarly, an interaction was observed between DT and A/D that predicted risk for AN.Discussion: Having elevated DT and A/D scores may increase risk for eating disorder symptomatology above and beyond a high score on either alone. Findings suggest that cluster modeling based on DT and A/D may be useful to inform novel and useful intervention strategies for AN and BN in adolescents.
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| 13. |
- Schwabecker, Julia
(författare)
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Between the Paths of Modernity : The European Commission’s Shaping of European Nuclear Energy Policy between 1999 and 2012
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A powerful symbol of modernity, in its early days, nuclear energy was associated with images of progress and dreams of a better life. At the start of the European process of integration, it was hoped that peaceful cooperation in nuclear matters would bring about lasting peace in the European continent. Today, the idea of uniting European nations through the common development of electronuclear technology may appear odd. Yet, more than a half century after the start of the European project of integration, the Euratom Treaty firmly calls for the creation of conditions necessary for the speedy establishment and growth of the nuclear industry, while the European Commission, an organization situated at the heart of the European integration project, officially frames this energy source as indispensable for the long-term transformation of the European energy system in a more sustainable direction.However, this development of European nuclear energy policy was neither natural nor inevitable. General European energy policy was standing at a crossroads at the turn of the century and the European Commission’s official position was split between two fundamentally different understandings of the role of nuclear power. Starting in 1999, when the European Union raised the status of its commitment to sustainable development to a constitutional and legally binding objective, and ending the analysis with the post-Fukushima policy response in 2012, this study explores how the Commission shaped electronuclear policy in light of the Union’s commitment to sustainable development. Stressing the role of the operationalization of sustainable development in the general energy sector, it explores how a particular conceptualisation of the nuclear energy development trajectory came to be considered natural and desirable while the other conceptualization was marginalised and became increasingly less relevant, discussing the implications of this development for the process of transforming the European energy system. Drawing broadly on the critical constructivist approach, the study is based on the assumption that the normative structure of the international system, which is underpinned by the industrial society’s ideals about modernity, justifies disproportionate focus on technological and industrial development and exploitation of nature. Because states and supranational polities alike define and redefine their interests and identities within this normative fabric of international society which in turn reflects ideas about what is legitimate and desirable, the study reflects on the critical potential of the concept of sustainable development to transform this normative framework.
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| 14. |
- Spang, Anja, et al.
(författare)
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Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism
- 2019
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 4:7, s. 1138-1148
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Tidskriftsartikel (refereegranskat)abstract
- The origin of eukaryotes represents an unresolved puzzle in evolutionary biology. Current research suggests that eukaryotes evolved from a merger between a host of archaeal descent and an alphaproteobacterial endosymbiont. The discovery of the Asgard archaea, a proposed archaeal superphylum that includes Lokiarchaeota, Thorarchaeota, Odinarchaeota and Heimdallarchaeota suggested to comprise the closest archaeal relatives of eukaryotes, has helped to elucidate the identity of the putative archaeal host. Whereas Lokiarchaeota are assumed to employ a hydrogen-dependent metabolism, little is known about the metabolic potential of other members of the Asgard superphylum. We infer the central metabolic pathways of Asgard archaea using comparative genomics and phylogenetics to be able to refine current models for the origin of eukaryotes. Our analyses indicate that Thorarchaeota and Lokiarchaeota encode proteins necessary for carbon fixation via the Wood-Ljungdahl pathway and for obtaining reducing equivalents from organic substrates. By contrast, Heimdallarchaeum LC2 and LC3 genomes encode enzymes potentially enabling the oxidation of organic substrates using nitrate or oxygen as electron acceptors. The gene repertoire of Heimdallarchaeum AB125 and Odinarchaeum indicates that these organisms can ferment organic substrates and conserve energy by coupling ferredoxin reoxidation to respiratory proton reduction. Altogether, our genome analyses suggest that Asgard representatives are primarily organoheterotrophs with variable capacity for hydrogen consumption and production. On this basis, we propose the 'reverse flow model', an updated symbiogenetic model for the origin of eukaryotes that involves electron or hydrogen flow from an organoheterotrophic archaeal host to a bacterial symbiont.
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| 15. |
- Zaremba-Niedzwiedzka, Katarzyna, et al.
(författare)
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Asgard archaea illuminate the origin of eukaryotic cellular complexity
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7637, s. 353-
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Tidskriftsartikel (refereegranskat)abstract
- The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the 'Asgard' superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota. Asgard archaea affiliate with eukaryotes in phylogenomic analyses, and their genomes are enriched for proteins formerly considered specific to eukaryotes. Notably, thorarchaeal genomes encode several homologues of eukaryotic membrane-trafficking machinery components, including Sec23/24 and TRAPP domains. Furthermore, we identify thorarchaeal proteins with similar features to eukaryotic coat proteins involved in vesicle biogenesis. Our results expand the known repertoire of 'eukaryote-specific' proteins in Archaea, indicating that the archaeal host cell already contained many key components that govern eukaryotic cellular complexity.
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| 16. |
- Zemojtel-Piotrowska, Magdalena A., et al.
(författare)
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Measurement of Psychological Entitlement in 28 Countries
- 2017
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Ingår i: European Journal of Psychological Assessment. - : Hogrefe & Huber Publishers. - 1015-5759 .- 2151-2426. ; 33:3, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the cross-cultural validation of the Entitlement Attitudes Questionnaire, a tool designed to measure three facets of psychological entitlement: active, passive, and revenge entitlement. Active entitlement was defined as the tendency to protect individual rights based on self-worthiness. Passive entitlement was defined as the belief in obligations to and expectations toward other people and institutions for the fulfillment of the individual's needs. Revenge entitlement was defined as the tendency to protect one's individual rights when violated by others and the tendency to reciprocate insults. The 15-item EAQ was validated in a series of three studies: the first one on a general Polish sample (N = 1,900), the second one on a sample of Polish students (N = 199), and the third one on student samples from 28 countries (N = 5,979). A three-factor solution was confirmed across all samples. Examination of measurement equivalence indicated partial metric invariance of EAQ for all national samples. Discriminant and convergent validity of the EAQ was also confirmed.
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| 17. |
- Zetterberg, Eva, et al.
(författare)
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Platelet count kinetics following Interruption of antiretroviral treatment: Results from the SMART study.
- 2013
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Ingår i: AIDS. - 1473-5571. ; 27:1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). Follow up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. DESIGN: SMART patients from sites that determined platelets routinely. METHODS: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. RESULTS:: Platelet levels decreased in the DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels. CONCLUSION: Interrupting ART increases the risk of thrombocytopenia, but re-initiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related pro-coagulant activity requires further study.
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| 18. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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