| 1. |
- Chaudhari, Aditi, et al.
(författare)
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ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism
- 2016
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1861:11, s. 1643-1651
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Tidskriftsartikel (refereegranskat)abstract
- Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS.
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| 2. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Coordinated regulation of the metabolome and lipidome at the host-microbial interface
- 2010
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1801:3, s. 240-245
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Forskningsöversikt (refereegranskat)abstract
- The creative use of gnotobiotic animals, coupled with the development of modern metagenomic sequencing platforms and metabolomic profiling of biospecimens, has bestowed new insight into the remarkably intricate interface between the host mammal and its resident microbiota. As mutual benefactors, each partner exhibits evidence of adaptation: the host provides a hospitable habitat, giving consideration to its own species of origin, diet, genotype, geographical location, presence or absence of disease, and use of medications; the microbiota, in turn, configures its constituency, collective genome (microbiome), transcriptome, and metabolome to optimally suit its ecological niche. In this review, we discuss the mechanisms through which the gut microbiota and its host collaborate to regulate lipid metabolism, thereby influencing the metabolic response to nutrient intake and ultimately, the development of obesity and associated diseases such as lipotoxicity. These studies therefore demonstrate that the gut microbiota is an 'environmental' influence whose synergistic interdependence with its host strongly suggests that we are in fact 'supraorganisms'.
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| 3. |
- Chen, Jie, et al.
(författare)
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Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes
- 2006
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Ingår i: The European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 8:5, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes. METHODS AND RESULTS: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05). CONCLUSION: Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
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| 4. |
- Frithiof, Robert, et al.
(författare)
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Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study
- 2021
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 132:7, s. 1733-1740
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW). Methods: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients. Results: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes. Conclusions: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness. Significance: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 5. |
- Nordrum, Lene, et al.
(författare)
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Data commentary in science writing: Using a small, specialized corpus for formative self-assessment practices
- 2015
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Ingår i: Learner Corpora in Language Testing and Assessment [SCL 70]. - Amsterdam : John Benjamins Publishing Company. - 9789027203786 ; 70, s. 59-84, s. 59-83
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Bokkapitel (refereegranskat)abstract
- Data commentary, the verbal comment on visual material, is a complex area in science writing; yet, few studies in academic writing focus on it, and teaching material is often too generic to be of use for students. This chapter presents an approach to addressing the teaching and learning of data commentary in ESP writing courses within the science disciplines involving direct application of a small, specialized corpus of data commentaries drawn from published research articles and master theses, all annotated for rhetorical moves. We exemplify how formative self-assessment practices of data commentaries can be developed from corpus-informed computer-assisted learning activities combining bottom-up corpus analysis with top-down discourse analysis, and outline a methodology for self-assessment practices involving three general types of exercises. Our approach serves to illustrate how a small, specialized corpus and purposefully crafted learning activities can be designed to assist students in pursing ownership of task requirements and monitoring their learning through continuous self-assessment. Such facilitation is of crucial value today as pedagogical and curricular developments in science education increasingly emphasize students’ awareness of communicative practices.
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| 6. |
- Olofsson, Sven-Olof, 1947, et al.
(författare)
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Lipid droplets as dynamic organelles connecting storage and efflux of lipids.
- 2008
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1791:6, s. 448-458
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Tidskriftsartikel (refereegranskat)abstract
- Neutral lipids are stored in the cytosol in so-called lipid droplets. These are dynamic organelles with neutral lipids as the core surrounded by a monolayer of amphipathic lipids (phospholipids and cholesterol) and specific proteins (PAT proteins and proteins involved in the turnover of lipids and in the formation and trafficking of the droplets). Lipid droplets are formed at microsomal membranes as primordial droplets with a diameter of 0.1-0.4 microm and increase in size by fusion. In this article, we review the assembly and fusion of lipid droplets, and the processes involved in the secretion of triglycerides. Triglycerides are secreted from cells by two principally different processes. In the mammary gland, lipid droplets interact with specific regions of the plasma membrane and bud off with an envelope consisting of the membrane, to form milk globules. In the liver and intestine, very low-density lipoproteins (VLDL) and chylomicrons are secreted by using the secretory pathway of the cell. Finally, we briefly review the importance of lipid droplets in the development of insulin resistance and atherosclerosis.
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| 7. |
- Tang, W. H. Wilson, et al.
(författare)
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Prognostic value of gut microbe-generated metabolite phenylacetylglutamine in patients with heart failure
- 2024
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Ingår i: EUROPEAN JOURNAL OF HEART FAILURE. - 1388-9842 .- 1879-0844.
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Tidskriftsartikel (refereegranskat)abstract
- AimPhenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)-relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF.Methods and resultsFasting plasma PAGln levels were measured by stable-isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with stable HF from two large cohorts. All-cause mortality was assessed at 5-year follow-up in the Cleveland cohort, and HF, hospitalization, or mortality were assessed at 3-year follow-up in the Berlin cohort. Within the Cleveland cohort, median PAGln levels were 4.2 (interquartile range [IQR] 2.4-6.9) mu M. Highest quartile of PAGln was associated with 3.09-fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, estimated glomerular filtration rate, amino-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, left ventricular ejection fraction, ischaemic aetiology, and HF drug treatment, elevated PAGln levels remained predictive of 5-year mortality in quartile comparisons (adjusted hazard ratio [HR] [95% confidence interval, CI] for Q4 vs Q1: 1.64 [1.07-2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 [IQR 2.0-4.8] mu M), and PAGln levels were associated with a 1.92-fold increase in 3-year HF hospitalization or all-cause mortality risk (adjusted HR [95% CI] for Q4 vs Q1: 1.92 [1.02-3.61]). Prognostic value of PAGln appears to be independent of trimethylamine N-oxide levels.ConclusionHigh levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio-renal risk markers.
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| 8. |
- Yu, H., et al.
(författare)
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Improved triangle splitting based bi-objective optimization for community integrated energy systems with correlated uncertainties
- 2022
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Ingår i: Sustainable Energy Technologies and Assessments. - : Elsevier Ltd. - 2213-1388 .- 2213-1396. ; 49
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Tidskriftsartikel (refereegranskat)abstract
- Economic and environmental benefits are the most important in the operation of community integrated energy systems (CIES), modeled as a bi-objective optimization problem. In the case of the uncertainties from loads and renewable energy generators, the effectiveness of the operation strategies may be degraded in the practical applications of CIES. In this paper, an improved triangle splitting based bi-objective optimization method is proposed to search for the Pareto optimal solution of the CIES operation. The general preference of decision-makers in practical applications is utilized in the search process to reduce the detailed search interval and consequently improve the optimization efficiency. In addition, a bi-objective uncertain optimization framework is established for the economic-environmental operation of the CIES under uncertainties. The correlation between uncertainties is considered to generate the operation scenarios, in which the solution probability function is employed to determine the final operation strategy with robustness. A comprehensive case study is conducted based on a practical CIES in China, proving the feasibility and effectiveness of the proposed methods.
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| 9. |
- Yucel, Yasemin Duygu, et al.
(författare)
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LiFePO4-coated carbon fibers as positive electrodes in structural batteries : Insights from spray coating technique
- 2024
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Ingår i: Electrochemistry communications. - : Elsevier BV. - 1388-2481 .- 1873-1902. ; 160, s. 107670-
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Tidskriftsartikel (refereegranskat)abstract
- This study presents the fabrication of LiFePO4 (LFP)-coated carbon fibers (CFs) as a positive electrode component for structural batteries, utilizing a spray coating technique. The successful coating of CFs through this method demonstrated their usefulness as efficient current collectors. The electrodes obtained using this method underwent electrochemical evaluations. Throughout the extended cycling tests at C/7, the maximum specific discharge capacity reached 146 mAh/g, maintaining a 77% capacity retention after 100 cycles. In rate performance assessments at the faster C-rate of 1.5C, the capacity measured 123 mAh/g, with a retention of 96%. The application of spray coating emerges as a promising technique for electrode production in structural batteries, showcasing its potential for optimizing performance in multifunctional energy storage systems.
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| 10. |
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