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- Chursa, Urszula, et al.
(författare)
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Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle.
- 2017
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:3, s. 553-567
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle.Skeletal muscle morphology was studied by histological examination, exercise performance and insulin sensitivity were assessed by treadmill running and euglycaemic-hyperinsulinaemic clamp, respectively, and muscle lipid metabolism was analysed by ex vivo assays in Stk25 transgenic and wild-type mice fed a high-fat diet. Lipid accumulation and mitochondrial function were also studied in rodent myoblasts overexpressing STK25. Global quantitative phosphoproteomics was performed in skeletal muscle of Stk25 transgenic and wild-type mice fed a high-fat diet to identify potential downstream mediators of STK25 action.We found that overexpression of STK25 in transgenic mice fed a high-fat diet increases intramyocellular lipid accumulation, impairs skeletal muscle mitochondrial function and sarcomeric ultrastructure, and induces perimysial and endomysial fibrosis, thereby reducing endurance exercise capacity and muscle insulin sensitivity. Furthermore, we observed enhanced lipid accumulation and impaired mitochondrial function in rodent myoblasts overexpressing STK25, demonstrating an autonomous action for STK25 within cells. Global phosphoproteomic analysis revealed alterations in the total abundance and phosphorylation status of different target proteins located predominantly to mitochondria and sarcomeric contractile elements in Stk25 transgenic vs wild-type muscle, respectively, providing a possible molecular mechanism for the observed phenotype.STK25 emerges as a new regulator of the complex interplay between lipid storage, mitochondrial energetics and insulin action in skeletal muscle, highlighting the potential of STK25 antagonists for type 2 diabetes treatment.
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| 2. |
- Gaines, Hans, et al.
(författare)
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Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2016
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:2, s. 93-98
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Forskningsöversikt (refereegranskat)abstract
- In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.
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| 4. |
- Johansson, Marcus, 1992, et al.
(författare)
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A TEST IMPLEMENTATION OF THE CORE MANUFACTURING SIMULATION DATA SPECIFICATION
- 2007
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Ingår i: Proceedings of the 2007 Winter Simulation Conference in Washington D.C. USA, December 9-12 2007. ; , s. 1673-1681
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Konferensbidrag (refereegranskat)abstract
- This paper describes an effort of testing the Core Manufacturing Simulation Data (CMSD) information model as a neutral data interface for a discrete event simulation model developed using Enterprise Dynamics. The implementation is based upon a model of a paint shop at a Volvo Car Corporation plant in Sweden. The model is built for a Swedish research project (FACTS), which focuses on the work procedure of developing new and modified production systems. FACTS has found standardized simulation data structures to be of high interest to achieve efficient data collection in conceptual stages of production development programs. For the CMSD-development team, implementations serve as an approach to validate the structures in CMSD and to gather requirements for future enhancements. CMSD was originally developed to support job shops, but the results of this implementation indicate a good possibility to extend CMSD to also support flow shops.
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| 8. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
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| 9. |
- Rydén, Magnus, 1975, et al.
(författare)
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Fe2O3 on Ce-, Ca- or Mg-stabilized ZrO2 as oxygen carrier for chemical-looping combustion using NiO as additive
- 2010
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Ingår i: AICHE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 56:8, s. 2211-2220
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen-carrier particles for chemical-looping combustion have been manufactured by freeze granulation. The particles consisted of 60 wt % Fe2O3 as active phase and 40 wt % stabilized ZrO2 as support material. Ce, Ca, or Mg was used to stabilize the ZrO2. The hardness and porosity of the particles were altered by varying the sintering temperature. The oxygen carriers were examined by redox experiments in a batch fluidized- bed reactor at 800–950°C, using CH4 as fuel. The experiments showed good reactivity between the particles and CH4. NiO was used as an additive and was found to reduce the fraction of unconverted CH4 with up to 80%. The combustion efficiency was 95.9% at best and was achieved using 57 kg oxygen carrier per MW fuel. Most produced oxygen carriers appear to have been decently stable, but using Ca as stabilizer resulting in uneven results. Further, particles sintered at high temperatures had a tendency to defluidize.
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| 10. |
- Rydén, Magnus, 1975, et al.
(författare)
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Ilmenite with addition of NiO as oxygen carrier for chemical-looping combustion
- 2010
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 89:11, s. 3523-3533
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Tidskriftsartikel (refereegranskat)abstract
- The naturally occurring mineral ilmenite, FeTiO3, has been examined as oxygen carrier for chemical-loopingcombustion. NiO-based particles have been used as an additive, in order to examine if it is possible toutilize the catalytic properties of metallic Ni to facilitate decomposition of hydrocarbons into more reactivecombustion intermediates such as CO and H2. Firstly, ilmenite was examined by oxidation and reductionexperiments in a batch fluidized-bed reactor. These experiments indicated moderate reactivitybetween ilmenite and CH4, which was used as reducing gas. However, adding 5 wt.% of NiO-based particlesto the ilmenite improved the conversion of CH4 greatly, resulting in an increase in combustion efficiencywith a factor of 3. Secondly, 83 h of chemical-looping combustion experiments were conducted ina small circulating fluidized-bed reactor, using ilmenite as oxygen carrier and natural gas as fuel. A widerange of process parameters and different levels of NiO addition were examined. Occasionally, there wereproblems with the circulation of solids between the air reactor and fuel reactor, but most of the time theexperiments worked well. The products were mostly CO2, H2O and unconverted CH4. Adding smallamounts of NiO-based particles to the reactor increased the conversion of the fuel considerably. Forthe base case conducted at 900, the combustion efficiency was 76% for pure ilmenite and 90% for thecorresponding experiments with 1 wt.% NiO-based particles added to the reactor. The properties ofilmenite were found to change considerably during operation. Used particles had lower density, weremore reactive and more porous than fresh particles. These changes appear to have been physical, andno unexpected chemical phases could be identified.
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