| 1. |
- Lindelöf, Linnea, et al.
(författare)
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A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
- 2024
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
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| 2. |
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| 3. |
- Sandholm, Kerstin, et al.
(författare)
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Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: C1q is a valuable biomarker of disease activity in systemic lupus erythematosus (SLE). The "gold standard" assay, rocket immunoelectrophoresis (RIE), is time-consuming, and thus a shift to soluble immune precipitation techniques such as nephelometry has occurred. However, quantification of C1q with these techniques has been questioned as a result of the antibody binding properties of C1q. In the present work, we have compared results using various techniques (RIE, nephelometry, and ELISA) and have developed and validated a new magnetic bead-based sandwich immunoassay (MBSI). Methods: C1q was quantified by nephelometry and the new sandwich immunoassay in 45 serum samples analyzed using RIE. C1q was also assessed in plasma using RIE and sandwich immunoassay in samples from SLE patients with nephritis (n = 69), SLE patients without nephritis (n = 310) as classified by BILAG score, and matched controls (n = 322). In addition, cerebrospinal fluid (CSF) samples from 31 patients, previously analyzed with ELISA, were also analyzed with the MBSI to test the behavior of this new assay in the lower detection range. Results: We found a strong correlation between the new MBSI, RIE, and ELISA, but not with nephelometry. The MBSI demonstrated lower levels of C1q in SLE patients than in matched controls (p < 0.0001), and patients with nephritis had lower levels than patients without nephritis (p < 0.01). Similarily, RIE showed significant differences between the patient groups (p < 0.0001). An association was also found between the levels of C1q and the SLE disease activity index (SLEDAI). Furthermore, there was good correlation between the values obtained by MBSI and ELISA, in both serum (r = 0.960) and CSF (r = 0.786), underscoring the ability of both techniques to measure low concentrations of C1q with high accuracy. Conclusion: The sandwich immunoassay correlated well with RIE, but soluble immune precipitation techniques, such as nephelometry, did not appear suitable alternatives, since C1q itself, and possibly anti-C1q antibodies, interfered with the measurements. The new sandwich immunoassay is therefore a good replacement for RIE in monitoring SLE disease activity.
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| 4. |
- Agvald, Per, et al.
(författare)
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Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism in rabbits
- 2006
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Ingår i: European Journal of Applied Physiology. - Heidelberg, Germany : Springer Berlin/Heidelberg. - 1439-6319 .- 1439-6327. ; 97:2, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery and trauma. We hypothesized that air emboli in the lung circulation might change expired nitric oxide (FeNO). A single intravenous infusion of air was given (100 mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A) one with intact NO production, (B) one with intact NO production and where end-tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L: -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P < 0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P < 0.05). Parallel to the NO increase there were significant decreases in end-tidal CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation pressure. In group B, when CO(2) was supplemented after air infusion, NO was suppressed (P = 0.033), but was still significantly elevated compared with pre-infusion control (P < 0.05). In group C, all animals died within 40 min of air infusion whereas all animals in the other groups were still alive at this time point. We conclude that venous air embolization increases FeNO, and that a part of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an intact NO production may be critical for the tolerance to VGE. Finally, FeNO might have a potential in the diagnosis and monitoring of pulmonary gas embolism.
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| 5. |
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| 6. |
- Ahrentorp, Fredrik, et al.
(författare)
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Sensitive magnetic biodetection using magnetic multi-core nanoparticles and RCA coils
- 2017
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Ingår i: Journal of Magnetism and Magnetic Materials. - : Elsevier BV. - 0304-8853 .- 1873-4766. ; 427, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- We use functionalized iron oxide magnetic multi-core particles of 100 nm in size (hydrodynamic particle diameter) and AC susceptometry (ACS) methods to measure the binding reactions between the magnetic nanoparticles (MNPs) and bio-analyte products produced from DNA segments using the rolling circle amplification (RCA) method. We use sensitive induction detection techniques in order to measure the ACS response. The DNA is amplified via RCA to generate RCA coils with a specific size that is dependent on the amplification time. After about 75 min of amplification we obtain an average RCA coil diameter of about 1 mu m. We determine a theoretical limit of detection (LOD) in the range of 11 attomole (corresponding to an analyte concentration of 55 fM for a sample volume of 200 mu L) from the ACS dynamic response after the MNPs have bound to the RCA coils and the measured ACS readout noise. We also discuss further possible improvements of the LOD.
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| 7. |
- Aksnes, Dag W., et al.
(författare)
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Arctic Research Trends : Bibliometrics 2016-2022
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This work was conducted by the UArctic Thematic Network on Research Analytics and Bibliometrics. It was supported by Global Affairs Canada through the Global Arctic Leadership Initiative.
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| 8. |
- Aksnes, Dag W., et al.
(författare)
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Arctic research trends : external funding 2016-2022
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report aims to provide an update to the two studies published in 2016 and 2017 (Osipov et al 2016 & 2017) with the primary task of assessing the global funding landscape around Arctic-related research. While the previous reports were focusing on the periods 2006-2015 and 2007-2016 respectively, this report covers 2016 to 2022, using the funding data from the Dimensions[1] dataset, which includes information from more than 600 funders and 7 million awarded grants with funding totalling $2.4 trillion+ (in US Dollars).The key findings of the updated report, based on the available data, highlight the following trends: · The fields of Earth Sciences (10.3 percent) and Environmental Science (5.5 percent) are the two largest recipients of Arctic research funding. · The US is the largest Arctic research nation in terms of total spending and number of projects started. It also has the most comprehensive coverage of funding sources in the dataset. · Canada and Russia are the second and third largest nations in terms of number of projects started, followed by Norway and Sweden.· UArctic institutions are central actors in Arctic research globally. · Researchers from Arctic Council Observer nations are financing a substantial amount of research on the Arctic. In particular, the UK and Japan finance a significant number of projects, followed by Germany and China with considerable numbers of Arctic-related research projects.· Funding from the European Union holds the position of the eighth-largest funder based on the number of projects awarded. The European Union is characterized by a few projects with large funding.· The analysis suggests that there is neither growth nor shrinkage in the relative volume of Arctic research funding over the period 2016–2022 in comparison with the growth of the general scientific community.· Private funders and foundations contribute little to Arctic research. Only one percent of the projects starting in 2016–2022 were funded privately. In general, the largest sources of external public funding for Arctic research come from the United States (US), Russia, Canada, and Norway, with the US being the biggest net contributor. Other kinds of funding, such as base budgets, are not described in this report. In addition, data on the public funding and funding amounts of Arctic research in Russia, Canada, and the Kingdom of Denmark are not always provided by the funders in project profiles, and net value is sometimes not disclosed by the funders themselves. This report specifically investigates projects initiated between 2016 and 2022, providing insights into the contemporary funding landscape of Arctic research. Understanding the geographical and institutional distribution of funding, as well as the specific areas of focus within this funding, holds significance for UArctic and Arctic Council officials. Such insights facilitate their ability to offer informed guidance to their respective members, aiding in the identification of strategic priorities.Moreover, gaining insights into the entities funding Arctic research, and those not engaged in such funding, holds importance for UArctic and Arctic Council science officers. Armed with information about Arctic-focused endeavours they can engage with funding bodies, fostering dialogue aimed at enhancing support, and collaboration for such initiatives.
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| 9. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 10. |
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