| 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. |
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| 3. |
- 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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| 4. |
- Khan, Omar M., 1980, et al.
(författare)
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Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
- 2011
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
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Tidskriftsartikel (refereegranskat)abstract
- RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
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| 5. |
- 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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| 6. |
- Aili, Katarina, 1980-, et al.
(författare)
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Sleep problems and fatigue as predictors for the onset of chronic widespread pain over a 5-and 18-year perspective
- 2018
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Ingår i: Bmc Musculoskeletal Disorders. - London : Springer Science and Business Media LLC. - 1471-2474. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious research suggests that sleep problems may be an important predictor for chronic widespread pain (CWP). With this study we investigated both sleep problems and fatigue as predictors for the onset of CWP over a 5-year and an 18-year perspective in a population free from CWP at baseline.MethodsTo get a more stable classification of CWP, we used a wash-out period, including only individuals who had not reported CWP at baseline (1998) and three years prior baseline (1995). In all, data from 1249 individuals entered the analyses for the 5-year follow-up and 791 entered for the 18-year follow-up. Difficulties initiating sleep, maintaining sleep, early morning awakening, non-restorative sleep and fatigue were investigated as predictors separately and simultaneously in binary logistic regression analyses.ResultsThe results showed that problems with initiating sleep, maintaining sleep, early awakening and non-restorative sleep predicted the onset of CWP over a 5-year (OR 1.85 to OR 2.27) and 18-year (OR 1.54 to OR 2.25) perspective irrespective of mental health (assessed by SF-36) at baseline. Also fatigue predicted the onset of CWP over the two-time perspectives (OR 3.70 and OR 2.36 respectively) when adjusting for mental health. Overall the effect of the sleep problems and fatigue on new onset CWP (over a 5-year perspective) was somewhat attenuated when adjusting for pain at baseline but remained significant for problems with early awakening, non-restorative sleep and fatigue. Problems with maintaining sleep predicted CWP 18years later irrespective of mental health and number of pain regions (OR 1.72). Reporting simultaneous problems with all four aspects of sleep was associated with the onset of CWP over a five-year and 18-yearperspective, irrespective of age, gender, socio economy, mental health and pain at baseline. Sleep problems and fatigue predicted the onset of CWP five years later irrespective of each other.ConclusionSleep problems and fatigue were both important predictors for the onset of CWP over a five-year perspective. Sleep problems was a stronger predictor in a longer time-perspective. The results highlight the importance of the assessment of sleep quality and fatigue in the clinic.
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| 7. |
- Amato, Alberto, et al.
(författare)
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Grazer-induced transcriptomic and metabolomic response of the chain-forming diatom Skeletonema marinoi
- 2018
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Ingår i: ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12, s. 1594-1604
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Tidskriftsartikel (refereegranskat)abstract
- Diatoms and copepods are main actors in marine food webs. The prey-predator interactions between them affect bloom dynamics, shape marine ecosystems and impact the energy transfer to higher trophic levels. Recently it has been demonstrated that the presence of grazers may affect the diatom prey beyond the direct effect of grazing. Here, we investigated the response of the chain-forming centric diatom Skeletonema marinoi to grazer cues, including changes in morphology, gene expression and metabolic profile. S. marinoi cells were incubated with Calanus finmarchicus or with Centropages typicus and in both cases responded by reducing the chain length, whereas changes in gene expression indicated an activation of stress response, changes in the lipid and nitrogen metabolism, in cell cycle regulation and in frustule formation. Transcripts linked to G protein-coupled receptors and to nitric oxide synthesis were differentially expressed suggesting involvement of these signalling transduction pathways in the response. Downregulation of a lipoxygenase in the transcriptomic data and of its products in the metabolomic data also indicate an involvement of oxylipins. Our data contribute to a better understanding of the gene function in diatoms, providing information on the nature of genes implicated in the interaction with grazers, a crucial process in marine ecosystems.
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| 8. |
- Andersson, Angelica, et al.
(författare)
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Long-distance mode choice estimation on joint travel survey and mobile phone network data
- 2024
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Ingår i: Sammanställning av referat från Transportforum 2024. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 91-92
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Both survey data and mobile phone network data are associated with benefits and limitations. Mobile phone network data is limited in its lack of ground truth for the bus and car split, in the lack of socio-economic information about the traveller, as well as in the lack of information about trip purpose. Survey data on the other hand nowadays often has too few observations to obtain significance in important parameters, and it is unlikely that they capture a representative sample of the population. In this paper we investigate to what extent combining the two data sources for mode choice demand model estimation can mitigate the challenges present when only using a single data source, as well as to what extent the estimation can be improved by adding variables unique to the survey data. We also provide recommendations for data collection and combination for future mode choice demand models and analyse policy implications of the estimated results. We show that in our case the business cost parameter becomes insignificant when basing the estimation on survey data only. The business cost parameter is important to compute values of travel times which are relevant for social cost benefit analyses. A benefit of combining the two data sources is that we can both identify latent class variables which capture the correct business group in the latent class structure of the mobile phone network data, and simultaneously obtain better estimates of those variables based on observations from the survey data. Most of the elasticity results in this paper are on par with previous studies; however our results suggest higher cross-elasticities in response to train travel time than what has previously been observed, which could have implications for the social valuation of investments in high speed rail. In this paper we have shown that the proposed method of data combination is indeed valid, and that by combining the two data sources we can mitigate the limitations of each separate data source and thus maintain good quality mode choice demand forecasting models, even in the face of declining survey response rates.
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| 9. |
- Andersson, Angelica, et al.
(författare)
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Long-distance mode choice model estimation using mobile phone network data
- 2022
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Ingår i: Journal of Choice Modelling. - : Elsevier. - 1755-5345. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we develop two methods for the use of mobile phone data to support the estimation of long-distance mode choice models. Both methods are based on logit formulations in which we define likelihood functions and use maximum likelihood estimation. Mobile phone data consists of information about a sequence of antennae that have detected each phone, so the mode choice is not actually observed. In the first trip-based method, the mode of each trip is inferred by a separate procedure, and the estimation process is then straightforward. However, since it is not always possible to determine the mode choice with certainty (although it is possible in the majority of cases), this method might give biased results. In our second antenna-based method we therefore base the likelihood function on the sequences of antennae that have detected the phones. The estimation aims at finding a parameter vector in the mode choice model that would explain the observed sequences best. The main challenge with the antenna-based method is the need for detailed resolution of the available data. In this paper we show the derivation of the two methods, that they coincide in case of certainty about the chosen mode and discuss the validity of assumptions and their advantages and disadvantages. Furthermore, we apply the first trip-based method to empirical data and compare the results of two different ways of implementing it.
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| 10. |
- Andersson, Angelica, et al.
(författare)
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Long-distance mode choice model estimation using mobile phone network data
- 2022
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Ingår i: Journal of Choice Modelling. - : Elsevier. - 1755-5345. ; 42
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we develop two methods for the use of mobile phone data to support the estimation of long-distance mode choice models. Both methods are based on logit formulations in which we define likelihood functions and use maximum likelihood estimation. Mobile phone data consists of information about a sequence of antennae that have detected each phone, so the mode choice is not actually observed. In the first trip-based method, the mode of each trip is inferred by a separate procedure, and the estimation process is then straightforward. However, since it is not always possible to determine the mode choice with certainty (although it is possible in the majority of cases), this method might give biased results. In our second antenna-based method we therefore base the likelihood function on the sequences of antennae that have detected the phones. The estimation aims at finding a parameter vector in the mode choice model that would explain the observed sequences best. The main challenge with the antenna-based method is the need for detailed resolution of the available data. In this paper we show the derivation of the two methods, that they coincide in case of certainty about the chosen mode and discuss the validity of assumptions and their advantages and disadvantages. Furthermore, we apply the first trip-based method to empirical data and compare the results of two different ways of implementing it.
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