| 1. |
- Brown, Jeffrey N, et al.
(författare)
-
AQUEOUSANDLIPID NUCLEAR MAGNETIC RESONANCE METABOLOMIC PROFILES OF THE EARTHWORM APORRECTODEA CALIGINOSA SHOW POTENTIAL AS AN INDICATOR SPECIES FOR ENVIRONMENTAL METABOLOMICS
- 2014
-
Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268. ; 33:10, s. 2313-2322
-
Tidskriftsartikel (refereegranskat)abstract
- The common pasture earthworm Aporrectodea caliginosa has often been neglected in environmental metabolomics in favor of species easily bred in the laboratory. The present study assigns aqueous metabolites in A. caliginosa using high-resolution 1- and 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. In total, 51 aqueous metabolites were identified, including typical amino acids (alanine, leucine, asparagine, phenylalanine), sugars (maltose, glucose), the dominant earthworm-specific 2-hexyl-5-ethyl-furansulfonate, and several previously unreported metabolites (oxoglutarate, putrescine). Examining the lesser-known earthworm lipid metabolome showed various lipid fatty acyl chains, cholesterol, and phosphatidylcholine. To briefly test if the NMR metabolomic techniques could differentiate A. caliginosa from different sites, earthworms were collected from 2 adjacent farms. Orthogonal partial least squares discriminant analysis detected metabolomic differences, suggesting the worms from the 2 sites differed in their energy metabolism, as indicated by altered levels of alanine, glutamine, glutamate, malate, fumarate, and lipids. Evidence of greater utilization of lipid energy reserves and onset of protein catabolism was also present. While the precise cause of the metabolomic differences could not be determined, the results show the potential of this species for further environmental metabolomic studies. Environ Toxicol Chem 2014;33:2313-2322. (c) 2014 SETAC
|
|
| 2. |
- Kullgren, Andreas, 1977, et al.
(författare)
-
A metabolomics approach to elucidate effects of food deprivation in juvenile rainbow trout (Oncorhynchus mykiss)
- 2010
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 299:6
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate whether NMR-based metabolomics is a suitable method to generate an integrated view on metabolic processes during food deprivation in salmonid fish. Juvenile rainbow trout (Oncorhynchus mykiss) weighing 43-115 g were either fed ad libitum or deprived of food for 28 days at 10 degrees C to investigate catabolic effects on energy reserves and metabolite patterns. The NMR analysis of plasma, liver, and muscle extracts revealed significant fasting-induced changes in the metabolome. Altered plasma lipoprotein levels and tissue-specific patterns of fatty acid mobilization were the most prominent responses, emphasizing the role of lipids as the primary energy source during fasting. In plasma, very-low-density lipoprotein levels increased in food-deprived fish compared with fed fish, whereas levels of high-density lipoprotein decreased. Signs of muscle protein catabolism were also observed as changes in the alanine dynamics. The results further suggest that mechanisms to preserve liver glycogen are present in the food-deprived fish. This study thus demonstrates the utility of NMR-based metabolomics of tissue extracts and plasma to describe the integrated metabolic status of fish.
|
|
| 3. |
- Kullgren, Andreas, 1977, et al.
(författare)
-
The impact of temperature on the metabolome and endocrine metabolic signals in Atlantic salmon (Salmo salar)
- 2013
-
Ingår i: Comparative Biochemistry and Physiology A. - : Elsevier BV. - 1095-6433 .- 1531-4332. ; 164:1, s. 44-53
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to elucidate the effects of elevated temperature on growth performance, growth- and appetite-regulating hormones and metabolism in Atlantic salmon, Salmo salar. Post-smolts in seawater (average mass 175 g) that had been reared at 12 °C were kept at three temperatures (8, 12 and 18 °C) and sampled after one and three months. After three months, the fish kept in 18 °C had decreased growth rate and condition factor, and elevated plasma levels of growth hormone (GH) and leptin, compared with fish kept at the lower temperatures. Food conversion efficiency was also decreased at 18 °C, while at the same time protein uptake was improved and thus was not a limiting mechanism for growth. Redistribution of energy stores in fish at the highest temperature is evident as a preference of maintaining length growth during times of limited energy availability. NMR-based metabolomics analyses of plasma revealed that several metabolites involved in energy metabolism were negatively affected by temperature in the upper temperature range of Atlantic salmon. Specifically, the high temperature induced a decline of several amino acids (glutamine, tyrosine and phenylalanine) and a shift in lipid metabolism. It appears likely that the decreased food intake at the highest temperature is linked to an anorexigenic function of leptin, but also that the decreased food intake, feed conversion efficiency and condition factor can be linked to changes in GH endocrinology.
|
|
| 4. |
|
|
| 5. |
- Malmberg, Erik, et al.
(författare)
-
Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML
- 2019
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:2, s. 409-417
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p <.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p <.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
|
|
| 6. |
- Samuelsson, Linda, 1973, et al.
(författare)
-
Contributions from metabolomics to fish research
- 2008
-
Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 4, s. 974-979
-
Forskningsöversikt (refereegranskat)
|
|
| 7. |
- Samuelsson, Linda, 1973-
(författare)
-
Methods for the Synthesis of PET Tracers and NMR Studies of Ribonuclease A
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis contains two parts.In the first part, general and versatile palladium-mediated 11C-C bond forming reactions for use in the production of radiotracers for Positron Emission Tomography (PET) were explored. Two complimentarty approaches were investigated: the coupling of [11C]methyl iodide with a vinyl stannane and the reaction of a [11C]methylated stannane with various organohalides. The former approach resulted in an improved, fully automated method for the synthesis of the potential cell proliferation tracer 1-(2’-deoxy-2’-fluoro-β-D-arabinofuranosyl)-[methyl-11C]- thymine. The tracer was obtained in an isolated decay-corrected radiochemical yield of 28% at 25 min after end of radionuclide production. In the latter approach, a [11C]methylated tricyclic stannane (5-[11C]methyl-1-aza- 5-stannabicyclo[3.3.3]undecane) was synthesised in 47% decay-corrected radiochemical yield, starting from [11C]methyl iodide. This stannane was successfully employed in palladium-mediated coupling reactions with aryl, heteroaryl and vinyl halides.In the second part, effects of the osmolytes glycine betaine, trimethylamine N-oxide (TMAO) and urea on Ribonuclease A (RNase A) were investigated using Nuclear Magnetic Resonance (NMR) spectroscopy. Changes in the enzymatic activity in the presence of these osmolytes at concentrations of ≤1 M were observed by monitoring the RNase A-catalysed degradation of polyuridylic acid using 31P NMR spectroscopy. The decrease in activity caused by urea was counteracted by both glycine betaine and TMAO at a molar ratio of 1:1.4 and 1:1, respectively.To investigate if the observed activity changes were accompanied by any detectable alteration in the gross conformation of RNase A, diffusion coefficients for the enzyme in the various osmolyte solutions were measured using pulsed-field gradient NMR. A pulse sequence suitable for diffusion measurements in highly concentrated aqueous osmolyte solutions was developed and assessed. The diffusion of RNase A was measured relative to a new internal standard, 2,2,5,5,-tetramethyl-1,4-dioxane. No clear, detectable change in the relative diffusion of RNase A was observed in these media.
|
|
| 8. |
- Samuelsson, Linda, 1973, et al.
(författare)
-
Reproducible (1)H NMR-Based Metabolomic Responses in Fish Exposed to Different Sewage Effluents in Two Separate Studies.
- 2011
-
Ingår i: Environmental science & technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 45:4, s. 1703-1710
-
Tidskriftsartikel (refereegranskat)abstract
- Treated sewage effluents contain complex mixtures of micropollutants, raising concerns about effects on aquatic organisms. The addition of advanced treatment steps has therefore been suggested. However, some of these could potentially produce effluents affecting exposed organisms by unknown modes of action. Here, (1)H NMR (proton nuclear magnetic resonance spectroscopy) metabolomics of fish blood plasma was used to explore potential responses not identified by more targeted (chemical or biological) assays. Rainbow trout was exposed in parallel to six differently treated effluents (e.g., conventional activated sludge, addition of sand filter, further addition of ozonation and/or a moving bed biofilm reactor or a separate membrane bioreactor line). Multivariate data analysis showed changes in the metabolome (HDL, LDL, VLDL and glycerol-containing lipids, cholesterol, glucose, phosphatidylcholine, glutamine, and alanine) between treatment groups. This formed the basis for postulating a hypothesis on how exposure to effluent treated by certain processes, including ozonation, would affect the metabolic profiles of exposed fish. The hypothesis withstood testing in an independent study the following year. To conclude, (1)H NMR metabolomics proved suitable for identifying physiological responses not identified by more targeted assays used in parallel studies. Whether these changes are linked to adverse effects remains to be tested.
|
|
| 9. |
- Samuelsson, Linda, 1973, et al.
(författare)
-
Using NMR metabolomics to identify responses of an environmental estrogen in blood plasma of fish
- 2006
-
Ingår i: Aquatic Toxicology (Amsterdam, Netherlands). - : Elsevier BV. - 0166-445X. ; 78:4, s. 341-349
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear magnetic resonance (NMR) based metabolomics in combination with multivariate data analysis may become valuable tools to study environmental effects of pharmaceuticals and other chemicals in aquatic organisms. To explore the usefulness of this approach in fish, we have used H-1 NMR metabolomics to compare blood plasma and plasma lipid extracts from rainbow trout exposed to the synthetic contraceptive estrogen ethinylestradiol (EE2) with plasma from control fish. The plasma metabolite profile was affected in fish exposed to 10 ng/L but not 0.87 ng/L of EE2, which was in agreement with an induced vitellogenin synthesis in the high dose group only, as measured by ELISA. The main affected metabolites were vitellogenin, alanine, phospholipids and cholesterol. The responses identified by this discovery-driven method could be put in context with previous knowledge of the effects of estrogens on fish. This adds confidence to the approach of using NMR metabolomics to identify environmental effects of pharmaceuticals and other contaminants. (c) 2006 Elsevier B.V. All rights reserved.
|
|
| 10. |
- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(författare)
-
Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.
- 2010
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m), (age 37+/-11 yrs), (BMI 24+/-3 kg/m(2)) direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA) were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT) technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index), was within the normal range (1.9-3.3) and MSNA was as expected for age and gender (13-44 burst/minute). RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005). RH-PAT index and MSNA were reciprocally related to time (h/week) spent on physical activity (p = 0.005 and p = 0.006 respectively) and platelet concentration (PLT) (p = 0.02 and p = 0.004 respectively). CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular health.
|
|
