| 1. |
- Linge, Carl Petrus, et al.
(författare)
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Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus
- 2022
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 122:9, s. 1486-1501
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Tidskriftsartikel (refereegranskat)abstract
- Background Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome. Methods Platelets were isolated from 23 patients with SLE. The five individuals with the highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared with platelets from five healthy controls. Data are available via ProteomeXchange with identifier PXD031202. Results Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserinebinding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥1.5 and a t-test p-value of ≤0.05 as cut-off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels were detected in platelets of normal size. Conclusion Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins, and autoantigens, largely independent of the platelet size and in agreement with an integrated role for platelets in SLE.
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| 2. |
- Wirestam, Lina, et al.
(författare)
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Low Intra-Individual Variation in Mean Platelet Volume Over Time in Systemic Lupus Erythematosus
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Platelets have recently emerged as important immune modulators in systemic lupus erythematosus (SLE), in addition to their role in thrombosis and cardiovascular disease. However, studies investigating mean platelet volume (MPV) in SLE are often scarce, conflicting and cross-sectional. In this study, MPV was measured in clinical routine throughout a defined time-period to quantify both individual MPV fluctuations and investigate if such variations are associated with disease activity and clinical phenotypes of SLE. Of our 212 patients, 34 patients had only one MPV value reported with the remaining 178 patients having between 2 and 19 visits with recorded MPV values. The intra-individual MPV variation was low, with a median variation of 0.7 fL. This was further supported by the finding that 84% of patients stayed within their reference interval category (i.e., small, normal or large) over time. In our cohort, no correlation between disease activity and MPV neither cross-sectionally nor longitudinally was found. Mean platelet volume values were significantly smaller in SLE patients (mean 10.5 fL) compared to controls (mean 10.8 fL), p < 0.0001. Based on the reference interval, 2.4% (n = 5) of patients had large-sized platelets, 84.4% (n = 179) had normal-sized and 13.2% (n = 28) had small-sized. A larger proportion (85.7%) of patients with small-sized platelets met the anti-dsDNA criterion (ACR10b; p = 0.003) compared to patients with normal and large (57.6%) sized platelets. In conclusion, the intra-individual MPV variation was of low magnitude and fluctuations in disease activity did not have any significant impact on MPV longitudinally. This lack of variability in MPV over time indicates that measuring MPV at any time-point is sufficient. Further studies are warranted to evaluate MPV as a possible biomarker in SLE, as well as to determine the underlying mechanisms influencing platelet size in SLE.
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| 3. |
- Zervides, Kristoffer A, et al.
(författare)
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Serum S100A8/A9 concentrations are associated with neuropsychiatric involvement in systemic lupus erythematosus: a cross-sectional study
- 2022
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Ingår i: BMC Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuropsychiatric (NP) involvement and fatigue are major problems in systemic lupus erythematosus (SLE). S100A8/A9 is a marker of inflammation and responds to therapy in SLE patients. S100A8/A9 has an immunopathogenic role in various neurological diseases. We investigated S100A8/A9 in relation to NP-involvement and fatigue in SLE.METHODS: 72 consecutive SLE outpatients at a tertiary centre and 26 healthy controls were included in this cross-sectional study. NPSLE was determined by specialists in rheumatology and neurology and defined according to three attribution models: "ACR", "SLICC A" and "SLICC B". Cerebral MRI was assessed by a neuroradiologist and neurocognitive testing by a neuropsychologist. The individuals were assessed by scores of pain (VAS), fatigue (VAS and FSS), and depression (MADRS-S). Concentrations of S100A8/A9 in serum and cerebrospinal fluid were measured with ELISA. Statistical calculations were performed using non-parametric methods.RESULTS: Serum concentrations of S100A8/A9 were higher in SLE patients compared with controls (medians 1230 ng/ml; 790 ng/ml, p = 0.023). The concentrations were higher in NPSLE patients compared with non-NPSLE patients when applying the SLICC A and ACR models, but not significant when applying the SLICC B model (medians 1400 ng/ml; 920 ng/ml, p = 0.011; 1560 ng/ml; 1090 ng/ml, p = 0.050; 1460 ng/ml; 1090 ng/ml, p = 0.083, respectively). No differences of CSF S100A8/A9 concentrations were observed between NPSLE and non-NPSLE patients. SLE patients with depression or cognitive dysfunction as an ACR NPSLE manifestation had higher serum S100A8/A9 concentrations than non-NPSLE patients (median 1460 ng/ml, p = 0.007 and 1380 ng/ml, p = 0.013, respectively). Higher serum S100A8/A9 correlated with higher VAS fatigue (r = 0.31; p = 0.008) and VAS pain (r = 0.27, p = 0.021) in SLE patients. Serum S100A8/A9 was not independently associated with NPSLE when adjusting for scores of fatigue (FSS) and pain (VAS) (OR 1.86, 95% CI 0.93-3.73, p = 0.08).CONCLUSIONS: Serum S100A8/A9 concentrations may be associated with NPSLE and fatigue. S100A8/A9 may be of interest in evaluating NPSLE, although further investigations are needed.
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| 4. |
- Bengtsson, Anders, et al.
(författare)
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SLE och graviditet - en utmaning
- 2021
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Ingår i: ReumaBulletinen. - 2000-2246. ; 145:2, s. 28-31
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Debette, Stéphanie, et al.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 6. |
- Edvardsen, Rolf Brudvik, et al.
(författare)
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Heterochiasmy and the establishment of gsdf as a novel sex determining gene in Atlantic halibut
- 2022
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly from a male and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male-only and female-only meiotic recombination regions (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4.5 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. Our findings indicate that heterochiasmy may facilitate the evolution of genetic sex determination systems relying on linkage of sexually antagonistic loci to a sex-determining factor. Author summaryEven closely related fish species can have different sex chromosomes, but this turn-over of sex determination systems is poorly understood. Here, we used large-scale genome sequencing to determine the DNA sequence of the Atlantic halibut chromosomes and compared sequencing data from males and females to identify the sex chromosomes. We show that males have much higher gene activity of the gene gonadal somatic cell derived factor (gsdf), which is located on the sex chromosomes and has a role in testicular development. The genome contains many mobile DNA sequences, transposable elements (TEs), one placed in front of gsdf, enhancing its activity. This made gsdf the sex determining factor, thereby creating a new Y-chromosome. We further describe how all Atlantic halibut chromosomes behave similar to sex chromosomes in that most regions only recombine in one sex. This phenomenon may contribute to the rapid turn-over of genetic sex determination systems in fish. Our results highlight the molecular events creating a new Y-chromosome and show that the new Atlantic halibut Y was formed less than 4.5 million years ago. Future studies in Atlantic halibut and closely related species can shed light on mechanisms contributing to sex chromosome evolution in fish.
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| 7. |
- Jern, Linnéa, et al.
(författare)
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Handball shot on goalkeeper’s head – How detrimental is it?
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the project was to evaluate the nature of the forces and accelerations affecting the head of a goalkeeper in handball when getting hit by a ball in the head. A ball hitting of the head might lead to a concussion, which is a general problem in the sport world. To get a better understanding of how common it is to get hit by a ball in the head as a handball player, a survey was sent out to the players of Swedish first league handball club Redbergslids IK. In order to find a correlation between the pressure, the velocity and the ball size drop tests were performed. During the drop tests the impact force time history and the ball velocity were measured. Concussions can be linked to large linear and rotational acceleration of the head. To be able to measure the linear and the rotational acceleration of the head during actual match situations, a test with a crash test dummy was created. The test featured players shooting on a (Hybrid III) crash test dummy’s head. The results from the drop tests were not sufficient enough to draw general conclusions on how the impulse is affected by pressure. In order to draw firm conclusions on how the ball pressure, ball size and velocity of the ball affects the impulse and force, more tests need to be performed. The dummy test showed that the parameter with the most effect on the head accelerations was the point of impact. The test resulted in linear acceleration of 41.7 ± 14.1 g and rotational acceleration of 1566.7 ± 505.4 rad/s2 in the dummy’s head. These numbers were in the same range for getting concussions as in other sports, e.g. baseball. Since there have not been enough research about concussions in handball it is currently not possible to state exactly when the hit is detrimental. Sammanfattning Syftet med projektet var att undersöka de krafter och de accelerationer som huvudet utsätts för då en handbollsmålvakt träffas av en boll i ansiktet. Speciellt undersöktes inverkan av bollstorlek och hastighet. Studien motiverades av att det är ett generellt problem i sportvärlden att vissa slag i huvudet kan leda till hjärnskakning. För att få en ökad förståelse för hur vanligt detta är i handboll genomfördes en enkätstudie bland junior- och seniorspelare i Redbergslids IK. Fallprov med handbollar mot en stel lastmätande träffyta genomfördes för att studera eventuella korrelationer mellan hastighet, tryck och bollstorlek gentemot krafthistoria. Under mer realistiska matchförhållanden genomfördes ytterligare ett test där spelare från Redbergslid IKs elitlag kastade handbollar på en krockdocka. I detta test mättes linjär och roterande acceleration av krockdockans huvud. Från fallprovet gick det inte att dra några slutgiltiga slutsatser angående hur impulsen påverkas av bolltrycket. Detta på grund av att resultaten inte var tillräckligt omfattande. För att kunna ge en definitiv beskrivning av hur bolltrycket, bollstorleken och hastigheten påverkar impuls och kraft skulle fler test behövas. Test med krockdocka visade att den parameter som hade mest påverkan på huvudets acceleration var vilken del av huvudet som blev träffad. Den linjära acceleration på huvudet fick ett utslag på 41.7 ± 14.1 g och vinkelaccelerationen på huvudet visade 1566.7 ± 505.4 rad/s2. Dessa siffor låg i samma intervall som för att få en hjärnskakning inom andra sporter, till exempel baseball. Eftersom att det inte finns tillräckligt mycket forskning om hjärnskakningar inom handbollen, var det inte möjligt att dra någon slutsats om hur skadligt det är att få en boll i huvudet.
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| 8. |
- Lundblad, Patrik, 1982-
(författare)
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Applied Geovisual Analytics and Storytelling
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 'Geovisual Analytics' represents a cross-disciplinary research that looks for innovative methods to interactively visualize and solve large spatio-temporal related visualization problems for multivariate data through a visual discovery, reasoning and collaborative process. The name emphasizes the link with the well-known research discipline of Visual Analytics and could be viewed as sub-area with its specific focus on space and time posing specific research problems.This thesis focuses on the design, implementation and evaluation of interactive analytical spatio-temporal and multivariate representations demonstrated in several application scenarios which contributes to our understanding of how technology, people and spatial representations of information work effectively together. Data are analysed through the use of coordinated and time-linked views controlled by a time slider. Trends are detected through several visual representations simultaneously, each of which is best suited to highlight different patterns and can help stimulate the analytical visual thinking process so characteristic for geovisual analytics reasoning. Interactive features include tooltips, brushing, highlight, visual inquiry, and conditioned statistics filter mechanisms that can discover outliers and simultaneously update all views.To support knowledge capture and the communication and publishing of gained insights from the data exploration process, a visual storytelling concept with snapshots is introduced where the author can capture the visual data exploration process and share it. Snapshots are memorized interactive visualization views that are captured and later on recreated, so that the reader of the story can see the same mental interactive scenario as the author of the story. These snapshots are then part of a story where the author writes an explanatory text and uses the snapshots to highlight key words. These highlights will allow the reader to recreate the data views used by the author and will guide the reader to the visual discoveries made.The contributions of this thesis are divided into two parts, where the first part includes applications based on geovisual analytics methods for exploring complex weather data and finding patterns and relationships within the data. Earlier, the use of data visualization has been very limited and the introduction of geovisual analytics and the techniques used have significantly improved the visual analysis process as well as increased the flexibility. The results of this research are today used by SMHI to improve optimization and safety of voyages and monitoring of the weather along Swedish roads. Formative evaluations were performed with domain analysts with the purpose to explore qualitative usability issues with respect to visual representations and interactive representation.Furthermore, this thesis contributes with a visual storytelling approach which aims at giving domain experts novel methods for capturing and sharing information discoveries in a way that the reader can follow the process of visual exploration. This approach has been tested and verified within the domain of public statistics, where national and regional statistics is published to the public through the use of embedded interactive visualizations and a story that can engage the reader. The concept of visual storytelling has also been introduced to educators, where stories are used as interactive teaching material for students to make national and regional statistics interactive and visually understandable to the students. It will also challenge the students to investigate new theories and then communicate them visually.
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| 9. |
- Löfdahl, Anna, et al.
(författare)
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Silver nanoparticles alter cell viability ex vivo and in vitro and induce proinflammatory effects in human lung fibroblasts
- 2020
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Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 µg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 µg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.
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| 10. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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