| 1. |
- Papp, Alexandra, et al.
(författare)
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Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Components of the extracellular matrix (ECM), when exposed to body fluids may promote local complement activation and inflammation. Pathologic complement activation at the glomerular basement membrane and at the Bruch’s membrane is implicated in renal and eye diseases, respectively. Binding of soluble complement inhibitors to the ECM, including factor H (FH), is important to prevent excessive complement activation. Since the FH-related (FHR) proteins FHR1 and FHR5 are also implicated in these diseases, our aim was to study whether these FHRs can also bind to ECM components and affect local FH activity and complement activation. Both FH and the FHRs showed variable binding to ECM components. We identified laminin, fibromodulin, osteoadherin and PRELP as ligands of FHR1 and FHR5, and found that FHR1 bound to these ECM components through its C-terminal complement control protein (CCP) domains 4-5, whereas FHR5 bound via its middle region, CCPs 3-7. Aggrecan, biglycan and decorin did not bind FH, FHR1 and FHR5. FHR5 also bound to immobilized C3b, a model of surface-deposited C3b, via CCPs 3-7. By contrast, soluble C3, C3(H2O), and the C3 fragments C3b, iC3b and C3d bound to CCPs 8-9 of FHR5. Properdin, which was previously described to bind via CCPs 1-2 to FHR5, did not bind in its physiologically occurring serum forms in our assays. FHR1 and FHR5 inhibited the binding of FH to the identified ECM proteins in a dose-dependent manner, which resulted in reduced FH cofactor activity. Moreover, both FHR1 and FHR5 enhanced alternative complement pathway activation on immobilized ECM proteins when exposed to human serum, resulting in the increased deposition of C3-fragments, factor B and C5b-9. Thus, our results identify novel ECM ligands of FH family proteins and indicate that FHR1 and FHR5 are competitive inhibitors of FH on ECM and, when bound to these ligands, they may enhance local complement activation and promote inflammation under pathological conditions.
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| 2. |
- Petersen, Julian, et al.
(författare)
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A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.
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| 3. |
- Bjarsch, Carin, 1973, et al.
(författare)
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Förstudierapport Medarbetarportalens framtid. En förbättrad internwebb i ny plattform
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna förstudie har utförts under 2021 inom ramen för GUSPP vid Göteborgs universitet. Förstudien har undersökt hur Medarbetarportalens roll och funktion kan ersättas av andra webbplattformar än InfoGlue. Universitetet behöver en ny Medarbetarportal av flera anledningar. Det mest akuta skälet är att dagens webbplattform Infoglue är föråldrad och kommer att stängas ner sommaren 2024. Andra tungt vägande skäl är att Medarbetarportalen inte lever upp till den nya lagen om på digital tillgänglighet, och att den inte upplevs som användarvänlig. Det är svårt att hitta rätt i den djupa sidstrukturen och portalens sökfunktion ger ofta ett dåligt sökresultat. Förstudiens rekommendation är att Sharepoint blir plattform för ny medarbetarportal. Med Sharepoint får medarbetarna ett modernt intranät och mer sammanhållen digital arbetsplats än idag. Det blir en enhetlig miljö att besöka för att hitta interninformation, verktyg, samarbete och dokumentlagring, vilket skapar en effektivare arbetsvardag för medarbetarna. Sharepoint innehåller mycket funktionalitet som är klar att använda, såsom en välfungerande sökfunktion och möjlighet att målgruppsanpassa informationsflödet. I Sharepoint finns också möjlighet att koppla ihop lokal och central information, vilket gör det lättare för medarbetare att hålla sig uppdaterade och minskar risken för dubbelpublicering av innehåll. Sharepointlösningen kan dock sättas upp på olika sätt. Hur lösningsarkitekturen ska designas behöver utredas initialt i kommande införandeprojekt. Förstudien har uppskattat kostnaden för ett införandeprojekt och tagit fram ett förslag på tidplan och projektorganisation.
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| 4. |
- Björkenheim, Anna, 1980-, et al.
(författare)
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Hereditary transthyretin amyloidosis caused by the rare Phe33Leu mutation
- 2020
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Ingår i: BMJ Case Reports. - : BMJ Publishing Group Ltd. - 1757-790X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary transthyretin amyloidosis is a rare progressive systemic disease. We describe a physically active 46-year-old man who presented with dyspnoea on exertion. An echocardiogram showed increased left ventricular wall thickness and diastolic dysfunction, but normal systolic function. The QRS voltage on ECG was normal. The patient was diagnosed with hypertrophic cardiomyopathy, and several years passed before establishment of the accurate diagnosis of hereditary transthyretin amyloidosis caused by the rare mutation ATTR Phe33Leu, previously described in only five case reports. Further investigation revealed neuropathy and nephropathy, and the patient developed severe heart failure. The patient is treated with tafamidis, has undergone heart transplantation and is currently planned for liver transplant. Hereditary transthyretin amyloidosis is likely underdiagnosed, especially in patients presenting with cardiomyopathy. A discrepancy between the left ventricular mass indicated by echocardiogram and that on ECG is an important indicator of amyloidosis, as is involvement of multiple organs.
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| 5. |
- Eriksson, Kimmo, et al.
(författare)
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Perceptions of the appropriate response to norm violation in 57 societies
- 2021
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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| 6. |
- Giustozzi, M., et al.
(författare)
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Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
- 2020
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Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
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| 7. |
- Johnson, Candice, et al.
(författare)
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Skin sensitization in silico protocol
- 2020
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducing a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.
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| 8. |
- Lichtenstein, Mia Beck, et al.
(författare)
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The Prevalence of Exercise Addiction Symptoms in a Sample of National Level Elite Athletes
- 2021
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Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media S.A.. - 2624-9367. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Exaggerated exercise volumes, lack of control, withdrawal symptoms and conflicts with family and friends are core symptoms of exercise addiction. The condition can lead to health problems and social isolation because exercise is given the highest priority in any situation. The prevalence of the risk of exercise addiction has mostly been assessed in leisure time exercisers such as runners, fitness attendees and cyclists. The prevalence proportion ranges from 3 to 42% depending on the type of sport and the assessment tool. The proportion is greater among elite athletes, and increases with the level of competition. This study's primary aim was to assess the prevalence of exercise addiction among elite athletes competing at national level and its secondary aim was to evaluate the psychometric properties of the Exercise Addition Inventory (EAI) in elite sports. Participants (n = 417) from 15 sports disciplines and with 51% women completed an online survey. Results showed that 7.6% were at risk of exercise addiction. This group was younger, exhibited tendency to exercise despite pain and injury, felt guilty if not exercising enough, and reported substantial eating disorder symptoms. The reliability and validity of the EAI was good suggesting that the scale is appropriate for measuring the risk of exercise addiction in elite athletes.
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| 9. |
- Marton, Zsuzsanna, et al.
(författare)
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Contrasting response of microeukaryotic and bacterial communities to the interplay of seasonality and local stressors in shallow soda lakes
- 2023
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Ingår i: FEMS Microbiology Ecology. - : Oxford University Press. - 0168-6496 .- 1574-6941. ; 99:9
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Tidskriftsartikel (refereegranskat)abstract
- Seasonal environmental variation is a leading driver of microbial planktonic community assembly and interactions. However, departures from usual seasonal trends are often reported. To understand the role of local stressors in modifying seasonal succession, we sampled fortnightly, throughout three seasons, five nearby shallow soda lakes exposed to identical seasonal and meteorological changes. We characterised their microeukaryotic and bacterial communities by amplicon sequencing of the 16S and 18S rRNA gene, respectively. Biological interactions were inferred by analyses of synchronous and time-shifted interaction networks, and the keystone taxa of the communities were topologically identified. The lakes showed similar succession patterns during the study period with spring being characterised by the relevance of trophic interactions and a certain level of community stability followed by a more dynamic and variable summer-autumn period. Adaptation to general seasonal changes happened through shared core microbiome of the lakes. Stochastic events such as desiccation disrupted common network attributes and introduced shifts from the prevalent seasonal trajectory. Our results demonstrated that, despite being extreme and highly variable habitats, shallow soda lakes exhibit certain similarities in the seasonality of their planktonic communities, yet local stressors such as droughts instigate deviations from prevalent trends to a greater extent for microeukaryotic than for bacterial communities.
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| 10. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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