| 1. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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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. |
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| 4. |
- 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
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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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| 5. |
- Hipkiss, Anna Maria, et al.
(författare)
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Teaching in Flexible Spatial and Digital Conditions
- 2021
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Ingår i: EARLI 2021. ; , s. 314-314
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Konferensbidrag (refereegranskat)abstract
- This study explores the opportunities and challenges of teaching under flexible spatial and digital conditions of the learning environment of a newly build school, analyzing how teaching is organized and what curricular genres can be discerned, what resources and practices are offered to stimulate students meaningmaking and what framing, relations and accessibility can be distinguished by the flexibility of furniture and classroom space. The analyses of a teacher team’s planning and teaching of the thematic work project on Space in years 2-3 (ages 8 to 9) and another teacher team’s thematic work project onCommunication in years 4-7 (ages10 to12) reveal varied teaching strategies between teacher-led and student-centered forms offering students linguistic, visual and audiovisual resources to make meaning of shared content in different school subjects. The young students practice reading comprehension, both of written texts and films, that also serves their knowledge-building about space. The older students display skills relating to different subjects through different technological and digital resources.
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| 6. |
- Hjalmarsson, Clara, 1969, et al.
(författare)
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Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke
- 2014
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Ingår i: Journal of Central Nervous System Disease. - 1179-5735. ; 19:6, s. 51-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS: A total of 20 patients (mean age 76 years) were included within 5-10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS: Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann-Whitney test). CONCLUSIONS: Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.
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| 7. |
- Pirazzi, Carlo, et al.
(författare)
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PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:15, s. 4077-4085
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.
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| 8. |
- Sandahl, Johan, 1974-, et al.
(författare)
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Överdrivna slutsatser om gymnasieelevers demokratikunskaper
- 2022
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Ingår i: Skola & Samhälle [S.O.S] Webbtidskrift. - : Föreningen Skola & Samhälle - webbtidskrift. - 2001-6727.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Rapporten från Stiftelsen Rättsfonden om gymnasieelevers kunskaper om demokrati har både metodologiska och teoretiska brister. Eftersom rapporten saknar stöd för flera av de rekommendationer som lämnas är risken att föreslagna förändringar inte gör någon skillnad eller i värsta fall leder i fel riktning, skriver Johan Sandahl med flera, alla forskare i samhällsvetenskapernas didaktik.
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| 9. |
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| 10. |
- Sofkova Hashemi, Sylvana, 1969-, et al.
(författare)
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Tema, rum och digitalisering i ny skolverksamhet : Slutrapport från projektet Digiflex Didaktisk Design i Samverkan
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sveriges befolkning ökar och med det följer om- och nybyggnation av skolor med förväntningar på innovativa skolmiljöer som erbjuder god arbetsmiljö för elever och lärare och främjar en modern, elevcentrerad och elevaktiv pedagogik. Detta projekt var baserat i en sådan nybyggd skola som erbjuder flexibilitet i variation av rum och öppna ytor, flyttbara möbler och digital teknologi i sin utformning.Syftet med projektet har varit att utveckla förståelse för den nybyggda skolans lärmiljö och studera hur skolans flexibla rumsliga och digitala ramar påverkar lärares undervisning och elevers kunskapsutveckling med utgångspunkt i följande frågeställningar:1. Hur används skolans fysiska och digitala rum i lärares undervisningsdesign?2. Hur kan elevers kunskapsutveckling stöttas genom rumslig och digital undervisningsdesign?3. Hur utnyttjas fysiska och digitala rum för att lyckas med det kompensatoriska uppdraget?Projektets har tillämpat co-design metoder, en kombination av aktionsforskning och design-baserad forskning, där lärare och forskare systematiskt och tillsammans studerat förändring och utveckling av undervisning i skolans lärmiljö över tid. Projektet har fokuserat på lärares didaktiska planering, undervisning och reflektion, möblering och rörelse i och mellan rummen, användning av digitala resurser, anpassning till elever samt ledarskapets roll. I utvecklingen av undervisningsdesign ingick kollegial planering, uppföljning, reflektion och re-design av undervisning i workshopsformat utifrån en tidigare utvecklad meta-tänkande modell för didaktisk design kallad Tanketärningar. Undervisningsdesignen har prövats i småskaliga interventioner och studerats genom observationer av lärares och elevers praktiker. En återkommande enkät har använts för att fånga lärarnas individuella röster. Dessutom genomfördes samtal och intervjuer med lärare och ledare på skolan.Resultaten visar på att skolans flexibla rumsliga och digitala lärmiljö ställer nya krav på lärare att tänka organisatoriskt runt elevflöden och digitala resurser i undervisningen. Lärares varierande rumsliga inramningar av undervisningen mellan fri rörlighet och statiska arrangemang ger möjligheter till olika relationsbyggande. Skolans goda digitala infrastruktur erbjuder lärarna ett multimodalt planeringsstöd och flexibilitet i feedback och anpassning av innehåll till eleverna. Dock kan den digitala undervisningen även framkalla hårt paketerad och ”klicka-sig-fram” undervisning som minskar lärares handlingsutrymme och elevinflytande. Lärare skolar in elever till en strukturerad flexibilitet för att hantera rumslig och digital variation som uppfattas även ge utrymme att möta eleverna individuellt när andra elever i gruppen arbetar mer självständigt. Samtidigt är inte lärmiljön anpassad för elever som kräver en högre grad av didaktiskt ledarskap.Samverkansambitioner har utmanats under projektets gång av coronapandemin men också oregelbundenheten i möten utöver workshoppar. Personalomsättning har påverkat relationsbygget mellan lärare och forskare över tid. Verksamhetens kollegiala arbete i lärarlag och ämnesövergripande undervisning utifrån ett fokus på tematiskt arbete har visat sig utmana lärarrollen, främst i de högre årskurserna. Projektets resultat pekar tydligt på vikten av kollegial samsyn och ledarskapets roll i det pedagogiska arbetet. Flexibiliteten behöver tolkas och kräver omfattande kollektiv planering i lärarlag som behöver ges tid och handlingsutrymme.Projektets resultat har spridits kontinuerligt genom skolans webbsida, vetenskapliga publikationer, presentationer och workshoppar på forskningskonferenser, föredrag i Göteborgs stad som listas i slutet på rapporten. En film har samproducerats om arbetet med tanketärningsmodellen. Under projektets gång producerades sex examensarbeten på lärarutbildningarna och en masteruppsats inom informatik. Masteruppsatsen skrevs om till ett vetenskapligt prisbelönt bidrag.
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