| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 2. |
- Andersson, Anders, et al.
(författare)
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Effects of Tobacco Smoke on IL-16 in CD8+ Cells from Human Airways and Blood: a Key Role for Oxygen Free Radicals?
- 2011
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Ingår i: AJP - Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504. ; 300:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in CD8(+) and CD4(+)cells as well as the CD4(+) chemo-attractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood, while at the same time increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro; in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased whereas other markers of key cellular functions (membrane integrity, apoptosis and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects whereas a protein synthesis inhibitor, a beta-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.
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| 3. |
- Andersson, Jan, et al.
(författare)
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Kartläggning av ägarskiften i företag : Utveckling och dokumentation av dataunderlag
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Myndigheten för tillväxtpolitiska utvärderingar och analyser, Tillväxtanalys, har haft i uppdrag av regeringen att genomföra kartläggning och analys av ägarskiften i företag. Uppdraget omfattade även att göra jämförelser mellan generationsskiften och andra typer av ägarskiften som inte är åldersbaserade samt belysa möjligheten att följa upp företagens skifte och dynamik över tid. Tillväxtanalys lämnade i oktober 2013 en delrapportering av uppdraget som avser dels en kartläggning av åldersstrukturen i företagsstocken, dels en fördjupad analys av ägarskiften. Denna rapport är en redovisning av uppdragets sista del som innebär utveckling och dokumentation av dataunderlag för identifiering av ägarförändringar.SCB har på uppdrag av Tillväxtanalys undersökt möjligheten att bättre identifiera ägarskiften genom att integrera och göra en matchningskontroll av kompletterande uppgifter gällande delägare i fåmansaktiebolag som kan hämtas från Skatteverket, SKV, med redan befintlig information om företagsdynamik, vilken finns i Företagens och arbetsställenas dynamik, FAD, och den registerbaserade arbetsmarknadsstatisken, RAMS, på SCB. För att göra detta studeras företagens ägarskiften mellan åren 2010 och 2011. Uppdraget omfattar även att beskriva FAD gällande syfte, metodik och innehåll.Cirka 80 procent av samtliga företag oberoende av bolagsform överlevde mellan åren 2010 och 2011. Resterande företag har på något sätt förändrats. Företag läggs ned och andra startar som en del i strukturomvandlingen. Dessutom ser vi att många företag och arbetsställen byter ägare. Näringslivet visar på en stor dynamik och dynamiken omfattar många olika typer av förändringar.Bearbetningarna visar att det med hjälp av RAMS och SKV:s register går att följa och framställa uppgifter om ägarförändringar på ett bra sätt. Detta gäller både för fåmansaktiebolag, där det går att följa individuellt ägande, och för övriga juridiska former där förändringar i organisationsnummer kan spåras, vilket indikerar ändrade ägarförhållanden. Analysen visar att SKV:s register är ett bra komplement till RAMS och FAD och tillför ytterligare information. Samkörningen av dessa registerdata ger mer information än vad som kan fås ut av respektive registerkällor separat. Det går dessutom att koppla på annan information om anställda, omsättning och olika mått på lönsamhet från andra register.Tillväxtanalys rekommenderar därför att SCB får tillgång till register gällande ägarandelar från Skatteverket under en längre tidsperiod än enbart de undersökta åren. Detta för att kunna sammanställa en databas som möjliggör bättre och mer precisa analyser av olika dimensioner av näringslivsdynamik och ägarförändringar. Det vore dessutom önskvärt att denna databas görs tillgänglig för forskning och studier som ökar kunskapen om olika dimensioner av näringslivets strukturomvandling.
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| 4. |
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| 5. |
- Chandrasekaran, Venkatagaran, et al.
(författare)
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Cohesin-Mediated Chromatin Interactions and Autoimmunity
- 2022
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Proper physiological functioning of any cell type requires ordered chromatin organization. In this context, cohesin complex performs important functions preventing premature separation of sister chromatids after DNA replication. In partnership with CCCTC-binding factor, it ensures insulator activity to organize enhancers and promoters within regulatory chromatin. Homozygous mutations and dysfunction of individual cohesin proteins are embryonically lethal in humans and mice, which limits in vivo research work to embryonic stem cells and progenitors. Conditional alleles of cohesin complex proteins have been generated to investigate their functional roles in greater detail at later developmental stages. Thus, genome regulation enabled by action of cohesin proteins is potentially crucial in lineage cell development, including immune homeostasis. In this review, we provide current knowledge on the role of cohesin complex in leukocyte maturation and adaptive immunity. Conditional knockout and shRNA-mediated inhibition of individual cohesin proteins in mice demonstrated their importance in haematopoiesis, adipogenesis and inflammation. Notably, these effects occur rather through changes in transcriptional gene regulation than through expected cell cycle defects. This positions cohesin at the crossroad of immune pathways including NF-kB, IL-6, and IFN gamma signaling. Cohesin proteins emerged as vital regulators at early developmental stages of thymocytes and B cells and after antigen challenge. Human genome-wide association studies are remarkably concordant with these findings and present associations between cohesin and rheumatoid arthritis, multiple sclerosis and HLA-B27 related chronic inflammatory conditions. Furthermore, bioinformatic prediction based on protein-protein interactions reveal a tight connection between the cohesin complex and immune relevant processes supporting the notion that cohesin will unearth new clues in regulation of autoimmunity.
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| 6. |
- Erlandsson, Malin, 1972, et al.
(författare)
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Survivin promotes a glycolytic switch in CD4+ T cells by suppressing the transcription of PFKFB3 in rheumatoid arthritis.
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:12
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explore the role of nuclear survivin in maintaining the effector phenotype of IFNγ-producing Tcells acting through the transcriptional control of glucose utilization. High expression of survivin in CD4+T cells was associated with IFNγ-dependent phenotype and anaerobic glycolysis. Transcriptome of CD4+ cells and sequencing of survivin-bound chromatin showed that nuclear survivin had a genome-wide and motif-specific binding to regulatory regions of the genes controlling cell metabolism. Survivin coprecipitates with transcription factors IRF1 and SMAD3, which repressed the transcription of the metabolic check-point enzyme phosphofructokinase 2 gene PFKFB3 and promoted anaerobic glycolysis. Combining transcriptome analyses of CD4+ cells and functional studies in glucose metabolism, we demonstrated that the inhibition of survivin reverted PFKFB3 production, inhibited glucose uptake, and reduces interferon effects in CD4+ cells. These results present a survivin-dependent mechanism in coordinating the metabolic adaptation of CD4+T cells and propose an attractive strategy to counteract IFNγ-dependent inflammation in autoimmunity.
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| 7. |
- Farias, Fabiana H. G., et al.
(författare)
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A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27, s. 432-441
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-U1-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.
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| 8. |
- Geijer, Cecilia, 1980, et al.
(författare)
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Initiation of the transcriptional response to hyperosmotic shock correlates with the potential for volume recovery.
- 2013
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Ingår i: The FEBS journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 280:16, s. 3854-67
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Tidskriftsartikel (refereegranskat)abstract
- The control of activity and localization of transcription factors is critical for appropriate transcriptional responses. In eukaryotes, signal transduction components such as mitogen-activated protein kinase (MAPK) shuttle into the nucleus to activate transcription. It is not known in detail how different amounts of nuclear MAPK over time affect the transcriptional response. In the present study, we aimed to address this issue by studying the high osmolarity glycerol (HOG) system in Saccharomyces cerevisiae. We employed a conditional osmotic system, which changes the period of the MAPK Hog1 signal independent of the initial stress level. We determined the dynamics of the Hog1 nuclear localization and cell volume by single-cell analysis in well-controlled microfluidics systems and compared the responses with the global transcriptional output of cell populations. We discovered that the onset of the initial transcriptional response correlates with the potential of cells for rapid adaptation; cells that are capable of recovering quickly initiate the transcriptional responses immediately, whereas cells that require longer time to adapt also respond later. This is reflected by Hog1 nuclear localization, Hog1 promoter association and the transcriptional response, but not Hog1 phosphorylation, suggesting that a presently uncharacterized rapid adaptive mechanism precedes the Hog1 nuclear response. Furthermore, we found that the period of Hog1 nuclear residence affects the amplitude of the transcriptional response rather than the spectrum of responsive genes.
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| 9. |
- Gravina, Giacomo, et al.
(författare)
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Survivin in autoimmune diseases.
- 2017
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Ingår i: Autoimmunity reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 16:8, s. 845-855
-
Forskningsöversikt (refereegranskat)abstract
- Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4(+) and CD8(+) memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.
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| 10. |
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| 11. |
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| 12. |
- Jarva, Erika, et al.
(författare)
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Aspects associated with health care professionals’ digital health competence development – a qualitative study
- 2022
-
Ingår i: Finnish Journal of eHealth and eWelfare. - Joroinen : Sosiaali- ja Terveyshuollon Tietojenkaesittely / Finnish Social and Health Informatics Association. - 1798-0798. ; 14:1, s. 79-91
-
Tidskriftsartikel (refereegranskat)abstract
- Health care professionals need continuous education to maintain the competencies required to provide high-quality care; in today’s world, this means an understanding of digital health services. Insight into health care professionals’ experiences of which aspects influence their digital health competence development is therefore highly relevant.The objective of the study was to examine which aspects influence the digital health competence development of health care professionals (nursing workforce and allied health professionals).In-depth, semi-structured interviews were conducted with 20 health care professionals (Finland n=15, Sweden n=5) from various health care settings between May 2019 and July 2020. Interviews were audio-recorded, translated verbatim and analysed with inductive content analysis.Health care professionals perceive that digital health competence development is influenced by aspects related to digital health adoption, co-workers and the work community, their manager, and opportunities for continuous education and orientation.The participants agreed that digital health competence is an important part of a health care professional’s overall clinical competence. Continuous education geared towards digital health competence should be systematically designed, and potentially integrate the resources available on social media platforms. Additionally, managers and supervisors should take a stronger stance towards learning about digital health services so they can serve as role models to their employees and genuinely promote digital health competence development.
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| 13. |
- Jensen, Maja, 1978, et al.
(författare)
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Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27
- 2023
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Ingår i: Iscience. ; 26:7
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates the role of survivin in epigenetic control of gene transcription through interaction with the polycomb repressive complex 2 (PRC2). PRC2 is responsible for silencing gene expression by trimethylating lysine 27 on histone 3. We observed differential expression of PRC2 subunits in CD4(+) T cells with varying levels of survivin expression, and ChIP-seq results indicated that survivin colocalizes with PRC2 along DNA. Inhibition of survivin resulted in a significant increase in H3K27 trimethylation, implying that survivin prevents PRC2 from functioning. Peptide microarray showed that survivin interacts with peptides from PRC2 subunits, and machine learning revealed that amino acid composition contains relevant information for predicting survivin interaction. NMR and BLI experiments supported the interaction of survivin with PRC2 subunit EZH2. Finally, protein-protein docking revealed that the survivin-EZH2 interaction interface overlaps with catalytic residues of EZH2, potentially inhibiting its H3K27 methylation activity. These findings suggest that survivin inhibits PRC2 function.
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| 14. |
- Järlskog, Ida, 1991, et al.
(författare)
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Traffic-related microplastic particles, metals, and organic pollutants in an urban area under reconstruction
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 774
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Tidskriftsartikel (refereegranskat)abstract
- In urban environments, particularly areas under reconstruction, metals, organic pollutants (OP), and microplastics (MP), are released in large amounts due to heavy traffic. Road runoff, a major transport route for urban pollutants, contributes significantly to a deteriorated water quality in receiving waters. This study was conducted in Gothenburg, Sweden, and is unique because it simultaneously investigates the occurrence of OP, metals, and MP on roads and in stormwater from an urban area under reconstruction. Correlations between the various pollutants were also explored. The study was carried out by collecting washwater and sweepsand generated from street sweeping, road surface sampling, and flow-proportional stormwater sampling on several occasions. The liquid and solid samples were analyzed for metals, polycyclic aromatic hydrocarbons (PAH), oxy-PAH, aliphatics, aromatics, phthalates, and MP. The occurrence of OP was also analyzed with a non-target screening method of selected samples. Microplastics, i.e. plastic fragments/fibers, paint fragments, tire wear particles (TWP) and bitumen, were analyzed with a method based on density separation with sodium iodide and identification with a stereo microscope, melt-tests, and tactile identification. MP concentrations amounted to 1500 particles/L in stormwater, 51,000 particles/L in washwater, and 2.6 × 106 particles/kg dw in sweepsand. In stormwater, washwater and sweepsand, MP ≥20 μm were found to be dominated by TWP (38%, 83% and 78%, respectively). The results confirm traffic as an important source to MP, OP, and metal emissions. Concentrations exceeding water and sediment quality guidelines for metals (e.g. Cu and Zn), PAH, phthalates, and aliphatic hydrocarbons in the C16–C35 fraction were found in most samples. The results show that the street sweeper collects large amounts of polluted materials and thereby prevents further spread of the pollutants to the receiving stormwater.
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| 15. |
- Lindén, Malin, et al.
(författare)
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FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex
- 2019
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Members of the human FET family of RNA-binding proteins, comprising FUS, EWSR1, and TAF15, are ubiquitously expressed and engage at several levels of gene regulation. Many sarcomas and leukemias are characterized by the expression of fusion oncogenes with FET genes as 5′ partners and alternative transcription factor-coding genes as 3′ partners. Here, we report that the N terminus of normal FET proteins and their oncogenic fusion counterparts interact with the SWI/SNF chromatin remodeling complex. In contrast to normal FET proteins, increased fractions of FET oncoproteins bind SWI/SNF, indicating a deregulated and enhanced interaction in cancer. Forced expression of FET oncogenes caused changes of global H3K27 trimethylation levels, accompanied by altered gene expression patterns suggesting a shift in the antagonistic balance between SWI/SNF and repressive polycomb group complexes. Thus, deregulation of SWI/SNF activity could provide a unifying pathogenic mechanism for the large group of tumors caused by FET fusion oncoproteins. These results may help to develop common strategies for therapy. © 2019 The Authors. Published under the terms of the CC BY 4.0 license
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| 16. |
- Lundqvist, Jenny, 1975-, et al.
(författare)
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Concomitant Infection Decreases the Malaria Burden but Escalates Relapsing Fever Borreliosis
- 2010
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 78:5, s. 1924-1930
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Tidskriftsartikel (refereegranskat)abstract
- About 500 million cases of malaria occur annually. However, a substantial number of patients who actually have relapsing fever (RF) Borrelia can be misdiagnosed with malaria due to similar manifestations and geographic distribution of the two diseases. More alarmingly, high prevalence of concomitant infections with malaria and RF Borrelia has been reported. Therefore, we used a mouse model to study the effects of such mixed infection. We observed a 21-fold increase in spirochete titers, whereas the numbers of parasitized erythrocytes were reduced 15-fold. This may be explained by polarization of the host immune response towards the intracellular malaria parasite, resulting in unaffected extracellular spirochetes and hosts that succumb to sepsis. Mixed infection also resulted in severe malaria anemia with low hemoglobin levels, even though the parasite counts were low. Overall, co-infected animals had higher fatality rate and shorter time to death than both malaria and RF single infection. Furthermore, secondary malaria infection reactivated a quiescent RF brain infection, which is the first evidence of a clinically and biologically relevant cue for reactivation of RF Borrelia infection. Our study highlights the importance of investigating concomitant infections in vivo to elucidate the immune responses that are involved in the clinical outcome.
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| 17. |
- Strandberg, Louise, 1981, et al.
(författare)
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Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
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| 18. |
- Wadell, M., et al.
(författare)
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Challenges imposed by the COVID-19 pandemic on the Obstetrics and Gynecology residency program: a mixed-methods Swedish survey in the COPE Staff cohort study
- 2022
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. Methods As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson's Chi-2-test for dichotomous data. The association between residents' worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. Results Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 +/- 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. Conclusion The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.
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| 19. |
- Åkerström, Magnus, 1981, et al.
(författare)
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The COPE Staff study : Study description and initial report regarding job satisfaction, work-life conflicts, stress, and burnout among Swedish maternal and neonatal healthcare workers during the COVID-19 pandemic
- 2023
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Ingår i: International Journal of Gynecology & Obstetrics. - : John Wiley & Sons. - 0020-7292 .- 1879-3479. ; 162:3, s. 989-997
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo describe the study design of the COPE Staff cohort study on working conditions for maternal and neonatal healthcare workers (MNHCWs), and present baseline data regarding job satisfaction, work-life conflicts, stress, and burnout. MethodsBetween January and April 2021, 957 MNHCWs (administrative and medical staff) completed a baseline survey. Average levels of job satisfaction, work-life conflicts, stress, and burnout, and associations to perceived workload were assessed. ResultsThe average levels of job satisfaction, work-life conflicts, stress, and burnout were 68.6 (95% confidence interval [CI] 64.3-72.8), 42.6 (95% CI 37.3-48.0), 42.0 (95% CI 37.7-46.3), and 1.9 (95% CI 1.6-2.2), respectively. The respondents scoring above critical values indicating clinical burnout ranged between 3% and 18%, respectively, for the four burnout sub-dimensions. Women reported significantly higher levels of stress and burnout. Younger participants had lower job satisfaction and higher levels of work-life conflicts, stress, and burnout. Higher perceived workload was significantly associated with lower job satisfaction levels and higher levels of work-life conflicts, stress, and burnout. ConclusionsOur results indicate associations between MNHCWs perceived workload and job satisfaction, work-life conflicts, stress, and burnout during the COVID-19 pandemic. Eighteen percent scored above critical values for exhaustion.
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| 20. |
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| 21. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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| 22. |
- Andersson, Anna-Maria, 1990-
(författare)
-
Mycobacterium tuberculosis and HIV coinfection : Effects on innate immunity and strategies to boost the immune response
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) still remains a big threat today, being the leading cause of death by a single infectious agent. The TB epidemic is fueled by HIV along with the increasing drug-resistance which prolongs the already long treatment duration and decreases the success rate for curing TB. In most cases an infection results in latency but HIV patients have a 20-30 times higher risk of developing active TB. There are around 36.9 million people living with HIV globally, with the highest burden in Africa. Although there are effective treatments against the disease, there is no cure for AIDS and the availability of the lifelong treatment is limited in low-income countries were the burden is highest. HIV infection causes an immunodeficiency characterized by the progressive loss of CD4 T cells which increases the risk of opportunistic infections, and infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb spreads through aerosols from one person with active tuberculosis to a healthy person. Upon inhalation the bacteria are phagocytosed by alveolar macrophages that secrete cytokines and chemokines to recruit more cells, such as dendritic cells, macrophages and lymphocytes, leading to the formation of a granuloma. During a single TB infection the bacteria are usually contained within the granuloma, but HIV can disrupt the stable granuloma, causing a rupture and dissemination of Mtb. This inflammatory site is also beneficial to HIV since it promotes replication of the virus within infected cells. HIV and Mtb are two successful intracellular pathogens able to avoid immune defense mechanisms both of the innate and adaptive immunity in order to persist and replicate. Their virulence factors can manipulate or inhibit cell signaling, phagosome maturation, autophagy, ROS production, apoptosis and antigen presentation, to promote survival. Boosting of immune defenses with host-directed therapies (HDT) has been proposed as a treatment strategy against TB, either alone or adjunctive to the current regimen.In this thesis, ways to boost the innate immune responses in Mtb and HIV coinfected macrophages were investigated, along with studies of the effect of HIV on Mtb antigen presentation in coinfected dendritic cells. The initial hypothesis was that autophagy induction through inhibition of mammalian target of rapamycin (mTOR) could suppress Mtb growth in HIV coinfected macrophages. However, during a low grade infection, autophagy induction increased Mtb replication due to a decreased autophagic flux and acidification of Mtb phagosomes. A general autophagic flux was induced, although not localized to the Mtb phagosomes, thus not inducing a xenophagy (autophagy of intracellular pathogens). Other ways of inducing autophagy or boosting the response in coinfected macrophages might be more beneficial and therefore the effect of efferocytosis was investigated. Uptake of apoptotic neutrophils by coinfected macrophages did not induce autophagy but enhanced the control of Mtb by other means. Upon efferocytosis, the macrophages acquired active myeloperoxidase (MPO) from the neutrophils that suppressed Mtb growth. The coinfected macrophages also produced more ROS after efferocytosis. The inhibition of Mtb growth could thus be mediated by MPO and the increased ROS production either directly or indirectly.The possibility to boost the innate immunity could prove to be important during an HIV coinfection, when the adaptive immunity is deficient. In addition to the well-known decline in CD4 T cells during the course of HIV progression, we found that HIV infection of dendritic cells inhibited antigen presentation by suppressing the expression of HLA-DR and co-stimulatory molecules on coinfected dendritic cells. Furthermore, HIV reduced secretion of pro-inflammatory cytokines and suppressed antigen processing through inhibition of autophagy. This impaired antigen presentation in coinfected dendritic cells resulted in a decreased activation and response of Mtb-specific CD4 T cells.In conclusion, this thesis shows how HIV can manipulate antigen presentation in Mtb coinfected dendritic cells and subsequently inhibit the adaptive immune response. It also contributes to insights on how efferocytosis of apoptotic neutrophils can boost the innate immune responses during coinfection. Lastly, autophagy induction through mTOR inhibition does not enhance protection against TB. Induction of autophagy should therefore be handled with care, particularly during HIV coinfection.
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| 23. |
- Andersson, Edvin K. W., et al.
(författare)
-
Initial SEI formation in LiBOB-, LiDFOB- and LiBF4-containing PEO electrolytes
- 2024
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 12:15, s. 9184-9199
-
Tidskriftsartikel (refereegranskat)abstract
- A limiting factor for solid polymer electrolyte (SPE)-based Li-batteries is the functionality of the electrolyte decomposition layer that is spontaneously formed at the Li metal anode. A deeper understanding of this layer will facilitate its improvement. This study investigates three SPEs – polyethylene oxide:lithium tetrafluoroborate (PEO:LiBF4), polyethylene oxide:lithium bis(oxalate)borate (PEO:LiBOB), and polyethylene oxide:lithium difluoro(oxalato)borate (PEO:LiDFOB) – using a combination of electrochemical impedance spectroscopy (EIS), galvanostatic cycling, in situ Li deposition photoelectron spectroscopy (PES), and ab initio molecular dynamics (AIMD) simulations. Through this combination, the cell performance of PEO:LiDFOB can be connected to the initial SPE decomposition at the anode interface. It is found that PEO:LiDFOB had the highest capacity retention, which is correlated to having the least decomposition at the interface. This indicates that the lower SPE decomposition at the interface still creates a more effective decomposition layer, which is capable of preventing further electrolyte decomposition. Moreover, the PES results indicate formation of polyethylene in the SEI in cells based on PEO electrolytes. This is supported by AIMD that shows a polyethylene formation pathway through free-radical polymerization of ethylene.
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| 24. |
- Andersson, Gerhard, et al.
(författare)
-
Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder
- 2012
-
Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 50:9, s. 544-550
-
Tidskriftsartikel (refereegranskat)abstract
- Guided internet-delivered cognitive behaviour therapy (ICBT) has been found to be effective in several controlled trials, but the mechanisms of change are largely unknown. Therapeutic alliance is a factor that has been studied in many psychotherapy trials, but the role of therapeutic alliance in ICBT is less well known. The present study investigated early alliance ratings in three separate samples. Participants from one sample of depressed individuals (N = 49), one sample of individuals with generalized anxiety disorder (N = 35), and one sample with social anxiety disorder (N = 90) completed the Working Alliance Inventory (WAI) modified for ICBT early in the treatment (weeks 3-4) when they took part in guided ICBT for their conditions. Results showed that alliance ratings were high in all three samples and that the WAI including the subscales of Task, Goal and Bond had high internal consistencies. Overall, correlations between the WAI and residualized change scores on the primary outcome measures were small and not statistically significant. We conclude that even if alliance ratings are in line with face-to-face studies, therapeutic alliance as measured by the WAI is probably less important in ICBT than in regular face-to-face psychotherapy.
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| 25. |
- Andersson, Johanna, 1983, et al.
(författare)
-
Lifetime Heterogeneity of DNA-Bound dppz Complexes Originates from Distinct Intercalation Geometries Determined by Complex-Complex Interactions
- 2013
-
Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 52:2, s. 1151-1159
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the extensive interest in structurally explaining the photophysics of DNA-bound [Ru(phen)(2)dppz](2+) and [Ru(bpy)(2)dppz](2+), the origin of the two distinct emission lifetimes of the pure enantiomers when intercalated into DNA has remained elusive. In this report, we have combined a photophysical characterization with a detailed isothermal titration calorimetry study to investigate the binding of the pure Delta and Lambda enantiomers of both complexes with [poly(dAdT)](2). We find that a binding model with two different binding geometries, proposed to be symmetric and canted intercalation from the minor groove, as recently reported in high-resolution X-ray structures, is required to appropriately explain the data. By assigning the long emission lifetime to the canted binding geometry, we can simultaneously fit both calorimetric data and the binding-density-dependent changes in the relative abundance of the two emission lifetimes using the same binding model. We find that all complex complex interactions are slightly unfavorable for Delta-[Ru(bpy)(2)dppz](2+), whereas interactions involving a complex canted away from a neighbor are favorable for the other three complexes. We also conclude that Delta-[Ru(bpy)(2)dppz](2+) preferably binds isolated, Delta-[Ru(phen)(2)dppz](2+) preferably binds as duplets of canted complexes, and that all complexes are reluctant to form longer consecutive sequences than triplets. We propose that this is due to an interplay of repulsive complex complex and attractive complex-DNA interactions modulated by allosteric DNA conformation changes that are largely affected by the nature of the ancillary ligands.
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| 26. |
- Andersson, Karin, 1972, et al.
(författare)
-
Survivin co-ordinates formation of follicular T-cells acting in synergy with Bcl-6
- 2015
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:24, s. 20043-20057
-
Tidskriftsartikel (refereegranskat)abstract
- Follicular T helper (Tfh) cells are recognized by the expression of CXCR5 and the transcriptional regulator Bcl-6. Tfh cells control B cell maturation and antibody production, and if deregulated, may lead to autoimmunity. Here, we study the role of the proto-oncogene survivin in the formation of Tfh cells. We show that blood Tfh cells of patients with the autoimmune condition rheumatoid arthritis, have intracellular expression of survivin. Survivin was co-localized with Bcl-6 in the nuclei of CXCR5(+)CD4 lymphocytes and was immunoprecipitated with the Bcl-6 responsive element of the target genes. Inhibition of survivin in arthritic mice led to the reduction of CXCR5(+) Tfh cells and to low production of autoantibodies. Exposure to survivin activated STAT3 and induced enrichment of PD-1(+)Bcl-6(+) subset within Tfh cells. Collectively, our study demonstrates that survivin belongs to the Tfh cell phenotype and ensures their optimal function by regulating transcriptional activity of Bcl-6.
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| 27. |
- Andersson, Klas, 1975, et al.
(författare)
-
Tillit och misstro i icke framgångsrika skolor
- 2018
-
Ingår i: Skolan som politisk organisation 3:e uppl, Maria Jarl, Jon Pierre (red.). - : Gleerups Utbildning AB. - 9789140696984
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Andersson, Maria, 1975, et al.
(författare)
-
Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure
- 2005
-
Ingår i: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 42:5, s. 441-52
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the global gene expression response of endothelium exposed to shear stress and intraluminal pressure and tested the hypothesis that the two biomechanical forces induce a differential gene expression response pattern. Intact living human conduit vessels (umbilical veins) were exposed to normal or high intraluminal pressure, or to low or high shear stress in combination with a physiological level of the other force in a unique vascular ex vivo perfusion system. Gene expression profiling was performed by the Affymetrix microarray technology on endothelial cells isolated from stimulated vessels. Biomechanical forces were found to regulate a very large number of genes in the vascular endothelium. In this study, 1,825 genes were responsive to mechanical forces, which corresponds to 17% of the expressed genes. Among pressure-responsive genes, 647 genes were upregulated and 519 genes were down regulated, and of shear stress-responsive genes, 133 genes were upregulated and 771 down regulated. The fraction of genes that responded to both pressure and shear stimulation was surprisingly low, only 13% of the regulated genes. Our results indicate that the two different stimuli induce distinct gene expression response patterns, which can also be observed when studying functional groups. Considering the low number of overlapping genes, we suggest that the endothelial cells can distinguish between shear stress and pressure stimulation.
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| 29. |
- Andersson, Martin O., et al.
(författare)
-
Co-infection with Babesia divergens and Anaplasma phagocytophilum in cattle (Bos taurus), Sweden
- 2017
-
Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 8:6, s. 933-935
-
Tidskriftsartikel (refereegranskat)abstract
- Babesiosis is a severe disease in cattle worldwide. In Europe, the main causative agent of bovine babesiosis is Babesia divergens. In some areas, this species is reported to have declined or even disappeared, and its etiological role overtaken by other piroplasmid species. Moreover, co-infection with other tick-transmitted pathogens can be expected to complicate diagnosis in cattle. Hence, molecular identification of the causative agent of babesiosis should be a priority. Therefore, samples from 71 domestic cattle, 39 with clinical signs of babesiosis and 32 without, from southern Sweden were screened for Babesia spp. and Anaplasma spp. using molecular methods Babesia divergens was detected in 38 of the samples, and Anaplasma phagocytophilum in 17. Co-infections with both pathogens were frequent, occurring in 18% of the animals with a B. divergens infection. The possibility of co-infection should be considered in diagnosis and treatment of bovine babesiosis.
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| 30. |
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| 31. |
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| 32. |
- Andree, Maria, et al.
(författare)
-
Knowledge Products from Close-To-Practice Research
- 2024
-
Ingår i: Round table presentation at the NERA-conference, 6-8 March, Malmö University.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ‘Close-to-practice research’ has received increased attention across the Nordic countries. Following the British Education Research Association (BERA), the notion of ‘close-to-practice research’ is used to refer to educational research that is based on problems in practice, often involves researchers working in partnership with practitioners in schools and addresses issues of relevance to practitioners. This roundtable focuses on how close-to-practice research can contribute to the knowledge base of the teaching profession by bringing together perspectives from didactics, school improvement and educational policy. More specifically, the interest is directed toward what characterizes the knowledge produced through practice-based research that may have significance for teachers' professional knowledge base and practice. The roundtable conversation builds on a previous analysis of what kinds of knowledge products are generated in didactic close-to-practice research where teachers and researchers work together within the research environment Stockholm Teaching & Learning Studies. As a result of this analysis a typology of knowledge products was proposed including: (i) descriptions of knowing, (ii) teaching design, (iii) didactic examples and (iv) methodological tools. It has been proposed that additional knowledge products may be developed, such as artifacts to be used in teaching (e.g. lesson plans, visual representations). The roundtable will include the following points of discussion: 1) a brief presentation of the typology, 2) challenging and developing the typology of knowledge products proposed by previous research by investigating different cases of close-to-practice research from traditions of action research and practice-developing research within subject-didactics, and 3) discussing how the notion of knowledge products may contribute to advancing the conversation on cumulativity in the field of educational research in general, and in relation to syntheses of close-to-practice research in particular. The participants will be engaged in conversations on the desirability and feasibility of striving towards cumulativity.
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| 33. |
- Berg, Frida, 1975-
(författare)
-
Genetic Analysis of Fat Metabolism in Domestic Pigs and their Wild Ancestor
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The domestication of the pig began about 9 000 years ago and many of the existing domestic breeds have been selected for phenotypic traits like lean meat and fast growth. Domestic pigs are phenotypically very different from the ancestral wild boar that has adapted to survive in their natural environment. Because of their divergence, crosses between domestic pigs and wild boars are suitable for constructing genetic maps and Quantitative trait locus (QTL) analyses. A cross between the Large White and the European wild boar was thus initiated in the late 1980s. A major QTL for fat deposition and growth, denoted FAT1, was found on chromosome 4. The aim of this thesis was to further characterise the FAT1 locus and to identify the causative gene(s) and mutation(s). We have identified new markers and constructed a high-resolution linkage and RH map of the FAT1 QTL interval. We also performed comparative mapping to the human genome and showed that the pig chromosome 4 is homologous to human chromosomes 1 and 8. The gene order is very well conserved between the two species. In parallel we have narrowed down the FAT1 QTL interval by repeated backcrossing to the domestic Large White breed for six generations. The QTL could be confirmed for fatness but not for growth. Furthermore, the data strongly suggested that there might be more than one gene underlying the FAT1 QTL. Depending on which hypothesis to consider, the one- or two-loci model, the FAT1 interval can be reduced to 3,3 or 20 centiMorgan (cM), respectively, based on the backcross experiments. In the last study we confirm the two-loci model with one locus primarily effecting abdominal fat and another locus primarily effecting subcutaneous fat. We have identified a missense mutation in the RXRG gene which is in strong association with the abdominal fat QTL and the mutation is a potential candidate for that locus.Brown adipose tissue (BAT) is a specific type of fat essential for non-shivering thermogenesis in mammals. Piglets appear to lack BAT and rely on shivering as the main mechanism for thermoregulation. Uncoupling protein 1 (UCP1) gene is exclusively expressed in BAT and its physiological role is to generate heat by uncoupling oxidative phosphorylation. We show that the UCP1 gene has been disrupted in the pig lineage about 20 years ago. The inactivation of UCP1 provides a genetic explanation for the poor thermoregulation in piglets.
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| 34. |
- Bergh, Niklas, 1979, et al.
(författare)
-
A new biomechanical perfusion system for ex vivo study of small biological intact vessels
- 2005
-
Ingår i: Ann Biomed Eng. - : Springer Science and Business Media LLC. - 0090-6964. ; 33:12, s. 1808-18
-
Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.
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| 35. |
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| 36. |
- Brogren, Helén, 1977, et al.
(författare)
-
Platelets synthesize large amounts of active plasminogen activator inhibitor 1
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:13, s. 3943-8
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAI-1 mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with (35)S-methionine followed by immunoprecipitation confirmed an ongoing PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA). This functional assay showed that the majority of the new protein was in an active configuration and could complex-bind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots.
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| 37. |
- Båth, Petra, 1988, et al.
(författare)
-
Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
- 2022
-
Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 78, s. 698-708
-
Tidskriftsartikel (refereegranskat)abstract
- Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 angstrom resolution when exposed to XFEL radiation, which is an improvement of 0.15 angstrom over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile Q(B) pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
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| 38. |
- Claeson, Magdalena, 1976, et al.
(författare)
-
Incidence of cutaneous melanoma in Western Sweden, 1970-2007.
- 2012
-
Ingår i: Melanoma research. - 1473-5636. ; 22:5, s. 392-8
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe the increasing incidence of cutaneous malignant melanoma (CMM) in Western Sweden during the period 1970-2007. A secondary aim was to show a geographical variation in incidence between coastal and inland areas, considering the effects of the local average duration of sunshine, and the sun exposure-related behavior in the populations. The Swedish Cancer Registry provided data on invasive melanomas during 1970-2007. Meteorological maps showed the annual average duration of sunshine during 1961-1990. A survey from 2007 with 2871 participants, carried out by the National Board of Health and Welfare, provided data on self-reported sun exposure. During the period studied, the age-standardized incidence for men in Western Sweden more than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to 27.1/100 000. Coastal areas, including Gothenburg city, had a high average duration of sunshine (1701-1900 h of sun/year), whereas inland areas had lower average duration of sunshine (≤1700 h). The incidence of CMM was higher in coastal areas and in Gothenburg city, compared with inland areas. This may be linked to ultraviolet radiation, a consequence of the higher average duration of sunshine. The sun exposure survey showed additional factors, which possibly led to the increased incidence, for example high sun exposure on holidays abroad. The alarming increase in the incidence of CMM in Western Sweden, during the period 1970-2007, shows the need for additional primary preventive measures, for example sun protection programs targeted at populations in this area.
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| 39. |
- Dolatabadi, Soheila, et al.
(författare)
-
FUS-DDIT3 Fusion Oncoprotein Expression Affects JAK-STAT Signaling in Myxoid Liposarcoma
- 2022
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma is one of the most common sarcoma entities characterized by FET fusion oncogenes. Despite a generally favorable prognosis of myxoid liposarcoma, chemotherapy resistance remains a clinical problem. This cancer stem cell property is associated with JAK-STAT signaling, but the link to the myxoid-liposarcoma-specific FET fusion oncogene FUS-DDIT3 is not known. Here, we show that ectopic expression of FUS-DDIT3 resulted in elevated levels of STAT3 and phosphorylated STAT3. RNA sequencing identified 126 genes that were regulated by both FUS-DDIT3 expression and JAK1/2 inhibition using ruxolitinib. Sixty-six of these genes were connected in a protein interaction network. Fifty-three and 29 of these genes were confirmed as FUS-DDIT3 and STAT3 targets, respectively, using public chromatin immunoprecipitation sequencing data sets. Enriched gene sets among the 126 regulated genes included processes related to cytokine signaling, adipocytokine signaling, and chromatin remodeling. We validated CD44 as a target gene of JAK1/2 inhibition and as a potential cancer stem cell marker in myxoid liposarcoma. Finally, we showed that FUS-DDIT3 interacted with phosphorylated STAT3 in association with subunits of the SWI/SNF chromatin remodeling complex and PRC2 repressive complex. Our data show that the function of FUS-DDIT3 is closely connected to JAK-STAT signaling. Detailed deciphering of molecular mechanisms behind tumor progression opens up new avenues for targeted therapies in sarcomas and leukemia characterized by FET fusion oncogenes.
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| 40. |
- Doroudi, Roya, 1967, et al.
(författare)
-
Methodological studies of multiple reference genes as endogenous controls in vascular gene expression studies
- 2005
-
Ingår i: Endothelium. - : Informa UK Limited. - 1062-3329 .- 1029-2373. ; 12:5-6, s. 215-23
-
Tidskriftsartikel (refereegranskat)abstract
- Detection and quantification of differentially expressed genes requires valid and reliable references to control for error variability introduced by preparatory procedures or efficiency of reverse transcription and polymerase chain reaction (PCR) amplification conditions. So-called housekeeping genes are frequently used as endogenous standards, based on the assumption that they are constitutively expressed and independent of experimental conditions. However, if the influence of experimental stimuli is to be analyzed, it cannot a priori be assumed that their expression is unaffected by stimulation. In the present study, the authors studied the expression of different housekeeping genes in the vascular endothelium of intact conduit vessels perfused in a unique biomechanical perfusion model. Ten control gene candidates were investigated by microarray expression analysis. Further, five of these genes were systematically analyzed by real-time reverse transcriptase (RT)-PCR gene quantification and their suitability as reference genes were evaluated. On the basis of these findings, the authors suggest criteria for evaluation of endogenous control genes in vascular perfusion studies.
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| 41. |
- Eriksson, Maria, 1969-, et al.
(författare)
-
Utvärdering av Mentorer i våldsprevention : Slutrapport
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten presenterar resultaten från en utvärdering av det våldsförebyggande programmet Mentorer i våldsprevention (MVP). Programmet Mentors in Violence Prevention kommer från USA och är ett utbildningsprogram som syftar till att förebygga killars och mäns våld. Organisationen Män för Jämställdhet har översatt programmet från engelska, anpassat det till svenska förhållanden och under perioden 2015-2017 spridit MVP i ett antal skolor i Sverige inom ramen för projektet ”En kommun fri från våld”. Det är den version av MVP som Män för Jämställdhet utvecklat och sprider som den här utvärderingen berör. Utvärderingen har genomförts på uppdrag av Skolverket.
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| 42. |
- Fridén-Saxin, Maria, 1979, et al.
(författare)
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Chroman-4-one and chromone based somatostatin beta-turn mimetics
- 2016
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234. ; 114, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- A scaffold approach has been used to develop somatostatin beta-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II' beta-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have K-i-values in the low mu M range when evaluated for their affinity for the sst2 and sst4 receptors. (C) 2016 Elsevier Masson SAS. All rights reserved.
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| 43. |
- Fridén-Saxin, Maria, 1979, et al.
(författare)
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Synthesis of 2-alkyl-substituted chromone derivatives using microwave irradiation.
- 2009
-
Ingår i: The Journal of organic chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 74:7, s. 2755-9
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Tidskriftsartikel (refereegranskat)abstract
- A base-promoted condensation between 2-hydroxyacetophenones and aliphatic aldehydes has been studied. The reaction has been optimized to afford 2-alkyl-substituted 4-chromanones in an efficient manner using microwave heating. Performing the reaction using diisopropylamine in EtOH at 170 degrees C for 1 h gave moderate to high yields (43-88%). The 4-chromanones could be further converted into highly functionalized 2,3,6,8-tetrasubstituted chromones in which a 3-substituent (acetate, amine, or bromine) was introduced via straightforward chemical transformations.
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| 44. |
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| 45. |
- Gøtzsche-Astrup, Oluf, et al.
(författare)
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Trust in interagency collaboration: The role of institutional logics and hybrid professionals
- 2023
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Ingår i: Journal of Professions and Organization. - : Oxford University Press (OUP). - 2051-8803 .- 2051-8811. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Interagency collaboration among social workers, teachers, and police is key to countering violent extremism in the Nordic countries by securing comprehensive assessment of cases of concern. Yet, previous research indicates that different institutional logics—perceptions of fundamental goals, strategies, and grounds for attention in efforts to counter violent extremists—exist across professions and challenge collaboration and trust building in practice. In this article, we empirically investigate these claims across social workers (n=1,105), teachers (n=1,387), and police (n=1,053) in four Nordic countries: Denmark, Sweden, Norway, and Finland. Using results from online surveys with professionals, we investigate the distribution of a ‘societal security logic’ and a ‘social care logic’ across professions and the degree to which these institutional logics translate into mutual trust. Through a comparison of institutional logics among practitioners with and without practical experience of interagency collaboration, we investigate whether and how institutional logics tend to mix and merge in hybrid organizational spaces. We conclude that differences in institutional logics across professions are differences in degree rather than in kind, but that such differences are important in shaping mutual trust and that experiences of interagency collaboration are correlated with a convergence toward a ‘social care logic’ conception of countering violent extremism.
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| 46. |
- Hansen, Anna, 1975-
(författare)
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Ordnade hushåll : Genus och kontroll i Jämtland under 1600-talet
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study is to investigate how households acted in order to create and uphold different norms, and the effect these norms had on the construction of gender. Throughout the thesis it is argued that control was an important way to enforce certain norms, and thus make daily life work. In this context control means to have the right knowledge and to act in the right way. If you had knowledge about the norms, you could act in accordance with them, and you could also draw attention to those who did not act as they were supposed to. The main focus is on the master and the mistress of the house, who were the key figures within the household. The investigated area is Jamtland, with some examples from surrounding areas.The control executed and displayed by different people concerned formal norms, such as legislation, semi-formal norms, such as certain religious texts, and informal norms and practices in the local community. The household’s ability to control these norms is analysed in connection to three main areas: control over resources, such as property and labour, control over the household, which often meant ability to obtain knowledge of what was going on, and finally, self-control. Furthermore this investigation deals with those exposed to control, how they reacted and at times tried to evade the control carried out by others.According to the theory of Tomas Laqueur, the similarities between men and women were strongly emphasised during the 17th century. This thesis shows that the power or authority of men and women was equal in many areas, but it differed in others. The small differences in the capacity of men and women to run the household, were important in the creation of gender.
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| 47. |
- Hendry, Alexandra, et al.
(författare)
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Inhibitory control and problem solving in early childhood : Exploring the burdens and benefits of high self-control
- 2022
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Ingår i: Infant and Child Development. - : John Wiley & Sons. - 1522-7227 .- 1522-7219. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- Low inhibitory control (IC) is sometimes associated with enhanced problem-solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem-solving task, amongst 102 English 2- and 3-year-olds (Study 1) and 84 Swedish children, seen at 18-months and 4-years (Study 2). Generativity during problem-solving was negatively associated with IC, as measured by prohibition-compliance (Study 1, both ages, Study 2 longitudinally from 18-months). High parent-reported IC was associated with poorer overall problem-solving success, and greater perseveration (Study 1, 3-year-olds only). Benefits of high parent-reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem-solving performance and IC as measured with a Delay-of-Gratification task (Study 2, concurrent associations at 4-years). We suggest that, for young children, high IC may confer burden on insight- and analytic-aspects of problem-solving.
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| 48. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 49. |
- Hultqvist, Sara, 1977-, et al.
(författare)
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Conditions for uptake of evidence-based knowledge in municipal care for older people in Sweden : a developmental evaluation
- 2022
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Ingår i: BMC Research Notes. - London : BioMed Central. - 1756-0500. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this paper is to describe the initial phase of a long-term collaboration initiative between a municipality and the Faculty of Medicine at a university in Sweden. The overall ambition of the collaboration is to strengthen the quality of care for older people. The concrete goal is to equip academically trained registered health care professionals (HCP) with tools for transferring evidence-based knowledge into practice. As municipal healthcare for older people is mainly carried out by staff lacking academic education, reg. HCP are key actors to bring in and consolidate an evidence-based approach in this setting. Developmental evaluation (DE) has been used to evaluate four separate activities in the initial phase. The activities where sequenced in a cumulative design to provide knowledge for further development of adequate tools.Results: The cumulative design originally planned did not fit the internal logic of the municipality. Therefore, workflow and pace adjustments were made to proceed towards the joint ambition; the creation of fruitful conditions for the uptake of evidence-based knowledge. Long-term collaboration between academia and organizations outside academia demands a sensitive and flexible research approach, recognizing that collaboration implies mutuality and restricts the sovereignty of academia in designing research.
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| 50. |
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