| 1. |
- Klein, C. F., et al.
(författare)
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In-hospital metabolite changes in infective endocarditis-a longitudinal H-1 NMR-based study
- 2019
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 38:8, s. 1553-1560
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of infective endocarditis (IE) is a 4-6-week provided course of intravenously administered antibiotics. The aim of this study was to investigate how serum metabolites as measured by proton nuclear magnetic resonance (H-1 NMR) spectroscopy are changing over time during the active phase of IE, and to see whether these metabolite changes might be used to monitor recovery in these patients. Patients hospitalized with first-time IE at Herlev Hospital, Denmark, from September 2015 to June 2017 were included. Longitudinal blood sampling was performed and serum was analyzed using H-1 NMR. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was used to separate sample groups and analyze differences in metabolite profiles. Thirteen patients were included in the study (77% men, median age 62 years (IQR 53-77)). All patients were cured during the hospitalization without any relapse during 6 months of follow-up. We analyzed 61 serum samples (median 5 samples, range 2-8 per person) drawn in the treatment period after IE diagnosis. The main changes during the in-hospital period were decreased levels of glucose, mannose, leucine, isoleucine, phenylalanine, tyrosine, and signals from polyols and N-acetylated protein. The metabolomic changes could in contrast to the routinely used parameters CRP and leucocyte levels distinguish between the early and late stages of disease treatment. We present the first longitudinal study of H-1 NMR metabolomics in patients with infective endocarditis. The metabolomic changes show a promising strength compared to routinely used clinical parameters.
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| 2. |
- Mukherjee, Vaskar, 1986, et al.
(författare)
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Phenomics, transcriptomics and metabolomics for identifying concentration-dependent chemical interactions and understanding the mechanistic basis of the mixture toxicity
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of mixtures of synthetic and natural chemicals in the environment is a growing concern for public health and environmental effects. Currently, most chemical legislations are based on the risk assessments carried out on individual substances and theoretical estimates of combination effect. However, exposure to multi-component mixtures may stimulate unpredicted overall toxic responses due to interactions, where interactions were scored as deviations from the independent action model. In our project, we investigated the frequency and magnitude of interactions in mixtures of five compounds - NaCl, HgCl2, paraquat, rapamycin, clotrimazole - with relatively known specific mode of action. Growth effects by all-combination pair-wise mixtures spanning a wide concentration range were investigated by employing high-resolution yeast phenomics. The baker’s/brewer’s yeast Saccharomyces cerevisiae and the marine yeast Debaryomyces hansenii are used in this study to identify evolutionary conserved mixture effects, with the aim to identify generic responses of relevance to a vast array of organisms. Our results clearly show that both synergistic and antagonistic relationships exist among the tested chemicals and some of these relationships are concentration-dependent. Evolutionary conserved interactions on the level of rate of growth were found for salt and rapamycin (synergy) as well as for salt and paraquat (antagonism). The mechanistic basis of the chemical interactions identified in our study was investigated by transcriptomics and metabolomics. As one example, we observed that several genes with symporter activity and with cation transmembrane transporter activity is downregulated in salt plus paraquat mixtures, while the expression of genes that are related to cofactor-dependent metabolic pathways is stimulated. We believe that the repression of symporter and ion transmembrane transport activity reduces paraquat entry to the yeast cells and thereby reduces its toxic response when combined with salt. On the other hand, upregulation of several of the genes (such as PGI1, PFK1, FBA1, and CDC19) related to cofactor-dependent metabolic pathways boost yeast fermentative activity. Since paraquat induces the production of reactive oxygen species (ROS) via respiration, a shift from aerobic respiration to anaerobic fermentation can reduce formation of ROS, thus reduces oxidative stress by paraquat.
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| 3. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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| 5. |
- Hall, Ulrika Andersson, et al.
(författare)
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Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes
- 2018
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753.
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Tidskriftsartikel (refereegranskat)abstract
- Aim. Determine the metabolic profile and identify risk factors of women transitioning from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM). Methods. 237 women diagnosed with GDM underwent an oral glucose tolerance test (OGTT), anthropometrics assessment, and completed lifestyle questionnaires six years after pregnancy. Blood was analysed for clinical variables (e.g., insulin, glucose, HbA1c, adiponectin, leptin, and lipid levels) and NMR metabolomics. Based on the OGTT, women were divided into three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Results. Six years after GDM, 19% of subjects had T2DM and 19% IGT. After BMI adjustment, the IGT group had lower HDL, higher leptin, and higher free fatty acid (FFA) levels, and the T2DM group higher triglyceride, FFA, and C-reactive protein levels than the NGT group. IGT and T2DM groups reported lower physical activity. NMR measurements revealed that levels of branched-chain amino acids (BCAAs) and the valine metabolite 3-hydroxyisobyturate were higher in T2DM and IGT groups and correlated with measures of insulin resistance and lipid metabolism. Conclusion. In addition to well-known clinical risk factors, BCAAs and 3-hydroxyisobyturate are potential markers to be evaluated as predictors of metabolic risk after pregnancy complicated by GDM.
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| 6. |
- Hall, Ulrika Andersson, et al.
(författare)
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Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake.
- 2018
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Ingår i: International journal of sport nutrition and exercise metabolism. - : Human Kinetics. - 1543-2742 .- 1526-484X. ; 28:1, s. 37-45
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated how post-exercise intake of placebo (PLA), protein (PRO) or carbohydrate (CHO) affected fat oxidation (FO) and metabolic parameters during recovery and subsequent exercise.In a cross-over design, 12 moderately trained women (VO2max 45 ± 6 ml·min(-1)·kg(-1)) performed three days of testing. A 23 min control (CON) incremental FO bike test (30-80% VO2max) was followed by 60 min exercise at 75% VO2max. Immediately post-exercise, subjects ingested PLA, 20 g PRO or 40 g CHO followed by a second FO bike test 2h later.Maximal fat oxidation (MFO) and the intensity at which MFO occurs (Fatmax) increased at the second FO test compared to the first following all three post-exercise drinks (MFO for CON=0.28±0.08, PLA=0.57±0.13, PRO=0.52±0.08, CHO=0.44±0.12 g fat·min(-1); Fatmax for CON=41±7, PLA=54±4, PRO=55±6, CHO=50±8 %VO2max, P<0.01 for all values compared to CON). Resting FO, MFO and Fatmax were not significantly different between PLA and PRO, but lower for CHO. PRO and CHO increased insulin levels at 1h post-exercise, though both glucose and insulin were equal with PLA at 2h. Increased post-exercise ketone levels only occurred with PLA.Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate intake dampened the increase in fat oxidation during the second test, though a significant increase was still observed compared to the first test.
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| 7. |
- Hall, Ulrika Andersson, et al.
(författare)
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Whole-body fat oxidation increases more by prior exercise than overnight fasting in elite endurance athletes.
- 2016
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Ingår i: Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme. - : Canadian Science Publishing. - 1715-5320. ; 41:4, s. 430-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to compare whole-body fat oxidation kinetics after prior exercise with overnight fasting in elite endurance athletes. Thirteen highly trained athletes (9 men and 4 women; maximal oxygen uptake: 66 ± 1 mL·min(-1)·kg(-1)) performed 3 identical submaximal incremental tests on a cycle ergometer using a cross-over design. A control test (CON) was performed 3 h after a standardized breakfast, a fasting test (FAST) 12 h after a standardized evening meal, and a postexercise test (EXER) after standardized breakfast, endurance exercise, and 2 h fasting recovery. The test consisted of 3 min each at 30%, 40%, 50%, 60%, 70%, and 80% of maximal oxygen uptake and fat oxidation rates were measured through indirect calorimetry. During CON, maximal fat oxidation rate was 0.51 ± 0.04 g·min(-1) compared with 0.69 ± 0.04 g·min(-1) in FAST (P < 0.01), and 0.89 ± 0.05 g·min(-1) in EXER (P < 0.01). Across all intensities, EXER was significantly higher than FAST and FAST was higher than CON (P < 0.01). Blood insulin levels were lower and free fatty acid and cortisol levels were higher at the start of EXER compared with CON and FAST (P < 0.05). Plasma nuclear magnetic resonance-metabolomics showed similar changes in both EXER and FAST, including increased levels of fatty acids and succinate. In conclusion, prior exercise significantly increases whole-body fat oxidation during submaximal exercise compared with overnight fasting. Already high rates of maximal fat oxidation in elite endurance athletes were increased by approximately 75% after prior exercise and fasting recovery.
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| 8. |
- Hansen, Lea B.S., et al.
(författare)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 9. |
- Kristiansen, Per Eugen, et al.
(författare)
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Nuclear Magnetic Resonance Structure and Mutational Analysis of the Lactococcin A Immunity Protein.
- 2016
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 55:45, s. 6250-6257
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Tidskriftsartikel (refereegranskat)abstract
- The class IId bacteriocin lactococcin A and the pediocin-like bacteriocins induce membrane leakage and cell death by specifically binding the mannose phophotransferase system (man-PTS) on their target cells. The bacteriocins' cognate immunity proteins that protect the producer cell from its own bacteriocin recognize and bind to the bacteriocin-man-PTS complex and thereby block membrane leakage. In this study, we have determined the three-dimensional structure of the lactococcin A immunity protein (LciA) by the use of nuclear magnetic resonance spectroscopy. LciA forms a four-helix bundle structure with a flexible C-terminal tail. Despite the low degree of sequence similarity between LciA and the pediocin-like immunity proteins, they share the same fold. However, there are certain differences between the structures. The C-terminal helix in LciA is considerably shorter than that observed in the pediocin-like immunity proteins, and the surface potentials of the immunity proteins differ. Truncated variants of LciA in which 6 or 10 of the C-terminal residues were removed yielded a reduced degree of protection, indicating that the unstructured C-terminal tail is important for the functionality of the immunity proteins.
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| 10. |
- Munch Roager, Henrik, et al.
(författare)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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