| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Andersson, Gerhard, et al.
(författare)
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Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder
- 2012
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 50:9, s. 544-550
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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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| 6. |
- Andersson, Johanna, 1983, et al.
(författare)
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Lifetime Heterogeneity of DNA-Bound dppz Complexes Originates from Distinct Intercalation Geometries Determined by Complex-Complex Interactions
- 2013
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 52:2, s. 1151-1159
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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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| 7. |
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| 8. |
- Claeson, Magdalena, 1976, et al.
(författare)
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Incidence of cutaneous melanoma in Western Sweden, 1970-2007.
- 2012
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Ingår i: Melanoma research. - 1473-5636. ; 22:5, s. 392-8
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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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| 9. |
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| 10. |
- Johansson, Maria E, 1977, et al.
(författare)
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alpha 7 Nicotinic Acetylcholine Receptor Is Expressed in Human Atherosclerosis and Inhibits Disease in Mice-Brief Report
- 2014
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Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 34:12, s. 2632-2636
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Tidskriftsartikel (refereegranskat)abstract
- Objective-Cholinergic pathways of the autonomic nervous system are known to modulate inflammation. Because atherosclerosis is a chronic inflammatory condition, we tested whether cholinergic signaling operates in this disease. We have analyzed the expression of the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) in human atherosclerotic plaques and studied its effects on the development of atherosclerosis in the hypercholesterolemic Ldlr(-/-) mouse model. Approach and Results-alpha 7nAChR protein was detected on T cells and macrophages in surgical specimens of human atherosclerotic plaques. To study the role of alpha 7nAChR signaling in atherosclerosis, male Ldlr(-/-) mice were lethally irradiated and reconstituted with bone marrow from wild-type or alpha 7nAChR-deficient animals. Ablation of hematopoietic cell alpha 7nAChR increased aortic atherosclerosis by 72%. This was accompanied by increased aortic interferon-gamma mRNA, implying increased Th1 activity in the absence of a7nAChR signaling. Conclusions-The present study shows that signaling through hematopoietic alpha 7nAChR inhibits atherosclerosis and suggests that it operates by modulating immune inflammation. Given the observation that alpha 7nAChR is expressed by T cells and macrophages in human plaques, our findings support the notion that cholinergic regulation may act to inhibit disease development also in man.
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| 11. |
- Pirazzi, Carlo, et al.
(författare)
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Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro
- 2012
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 57:6, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells, which secrete VLDL-sized apoB-containing lipoproteins. Methods: VLDL kinetics was analyzed after a bolus infusion of stable isotopes in 55 overweight/obese men genotyped for the PNPLA3 I148M variant. Intracellular lipid content, apoB secretion and glycerolipid metabolism were studied in McA-RH 7777 cells overexpressing the human 1481 wild type or 148M mutant PNPLA3 protein. Results: In humans, carriers of the PNPLA3 148M allele had increased liver fat compared to 1481 homozygotes, and kinetic analysis showed a relatively lower secretion of the large, triglyceride-rich VLDL (VLDL1) in 148M carriers vs. 1481 homozygotes for the same amount of liver fat. McA-RH 7777 cells overexpressing the 148M mutant protein showed a higher intracellular triglyceride content with a lower apoB secretion and fatty acid efflux, compared to cells overexpressing the 1481 wild type protein. The responses with 148M matched those observed in cells expressing the empty vector, indicating that the mutation results in loss of function. Conclusions: We have shown that PNPLA3 affects the secretion of apoB-containing lipoproteins both in humans and in vitro and that the 148M protein is a loss-of-function mutation. We propose that PNPLA3 148M promotes intracellular lipid accumulation in the liver by reducing the lipidation of VLDL.
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| 12. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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The TGR5 gene is expressed in human subcutaneous adipose tissue and is associated with obesity,Weight loss and resting metabolic rate
- 2013
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 433:4, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids have emerged as a new class of signaling molecules that play a role in metabolism. Studies in mice have shown that the bile acid receptor TGR5 mediates several of these effects but the metabolic function of TGR5 in humans is less well established. Here we show that human adipose tissue TGR5 expression is positively correlated to obesity and reduced during diet-induced weight loss. Adipose tissue TGR5 expression was also positively correlated to resting metabolic rate. Our study indicates that human adipose tissue contributes to the TGR5 mediated metabolic effects of bile acids and plays a role in energy expenditure. (C) 2013 Elsevier Inc. All rights reserved.
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| 13. |
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