| 1. |
- Dongiovanni, P., et al.
(författare)
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease
- 2015
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 61:2, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P<0.05), had more-severe steatosis, necroinflammation, ballooning, and fibrosis (P<0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23-2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25-0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P<0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (Hepatology 2015;61:506-514)
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| 2. |
- Ekman, Peter, 1969-, et al.
(författare)
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Customer Value Through Resource Integration : The Role of the Institutional Solution Space: An Abstract
- 2018
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Ingår i: Developments in Marketing Science: Proceedings of the Academy of Marketing Science. - Cham : Springer Nature. ; , s. 495-496
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Konferensbidrag (refereegranskat)abstract
- In this paper, we elaborate service-dominant (S-D) logic’s concept of resource integration as a premise for customer value co-creation and service provision. Following S-D logic, resource integration that results in customer value is dependent on institutions and institutional arrangements. S-D logic’s fifth axiom states: “Value co-creation is coordinated through actor-generated institutions and institutional arrangements” (Vargo & Lusch, 2016, page 18). We report on three case study findings to offer contextualized explanations that seek to join current conceptualizations with solid explanatory power. These cases span from the digitalization of music industry, sustainable strategies in the real estate industry, and insights from an innovation lab for open innovations. The empirical renderings are utilized to help to explain the institutional arrangements that are at play. The results show that the potential boundaries of, how, and which resources can be utilized and integrated are to great extent related to the perceived available “solution space” (von Hippel, 2001) or “opportunity space” (Normann, 2001) offered by the institutional and practice-related boundaries of the context (Ridell, Röndell, & Sörhammar, 2012). By integrating the ideas of a solution space and opportunity space with the later rendering of institutional arrangements as denominator for value creation, we contribute to the current mid-range theory development of S-D logic as well as a better understanding of value co-creation in practice. The introduced concept of institutional solution space combines the idiosyncratic needs of actors with the perceived – i.e., institutional and socio-material-derived – opportunities associated with resources. Thus, it offers a bridge between the abstract concepts of resource integration, value-in-context, and institutional arrangements (Vargo & Lusch, 2016). © 2018, Academy of Marketing Science.
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| 3. |
- Pärnamets, Philip, et al.
(författare)
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Memory distorions resulting from a choice blindness task
- 2015
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Ingår i: Proceedings of the 37th Annual Conference of the Cognitive Science Society. ; , s. 1823-1828
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Konferensbidrag (refereegranskat)abstract
- Using a choice blindness paradigm, it is possible to switch decisions and outcomes in simple choice tasks. Such switches have been found to carry over into later choices, hypothesized to be mediated by beliefs about earlier decisions. Here we investigated participants’ memories for stimuli in a simple choice blindness task involving preferential choices between pairs of faces. We probed participants’ recognition and source memory following a round of choices where on some trials participants were presented with the opposite face to the one they actually selected. We found no effect on recognition memory accuracy. Source memory was impaired such that participants failing to detect the manipulation later misremembered recognized non-chosen faces as being previously chosen. The findings are discussed in the light of self-perception theory and previous work on how beliefs affect memories for choices.
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| 4. |
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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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