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- Wegrzyn, Agnieszka B., et al.
(författare)
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Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease
- 2020
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 287:23, s. 5096-5113
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Tidskriftsartikel (refereegranskat)abstract
- Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal α-oxidation of the branched-chain fatty acid phytanic acid. The disorder presents with late-onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for RD, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. We used transcriptomics (available via GEO database with identifier GSE138379), metabolomics and proteomics (available via ProteomeXchange with identifier PXD015518) data, which we obtained from healthy controls and RD patient fibroblasts incubated with phytol, a precursor of phytanic acid. Our model correctly represents the metabolism of phytanate and displays fibroblast-specific metabolic functions. Using this model, we investigated the metabolic phenotype of RD at the genome scale, and we studied the effect of phytanate on cell metabolism. We identified 53 metabolites that were predicted to discriminate between healthy and RD patients, several of which with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy. Databases: Transcriptomics data are available via GEO database with identifier GSE138379, and proteomics data are available via ProteomeXchange with identifier PXD015518.
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| 6. |
- Hultgren, Kristoffer, et al.
(författare)
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What caused the exceptional mid-latitudinal Noctilucent Cloud event in July 2009?
- 2011
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Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 73:14-15, s. 2125-2131
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Tidskriftsartikel (refereegranskat)abstract
- Noctilucent Clouds (NLCs) are rarely observed at mid-latitudes. In July 2009, strong NLCs were recorded from both Paris and Nebraska, located at latitudes 48 degrees N and 41 degrees N, respectively. The main focus of this work is on the atmospheric conditions that have led to NLCs at these latitudes. We investigate to what extent these clouds may be explained by local formation or by transport from higher latitudes. The dynamical situation is analyzed in terms of wind fields created from Aura/MLS temperature data and measured by radar. We discuss possible tidal effects on the transport and examine the general planetary wave activity during these days. The winds do not seem sufficient to transport NLC particles long southward distances. Hence a local formation is rather likely. In order to investigate the possibility of local NLC formation, the CARMA microphysical model has been applied with temperature data from MLS as input. The results from the large-scale datasets are compared to NLC observations by Odin and to local NLC, temperature and wind measurements by lidar and radar. The reason for the exceptional NLC formation is most likely a combination of local temperature variations by diurnal tides, advantageously located large-scale planetary waves, and general mesospheric temperature conditions that were 5-10 K colder than in previous years. The results also point to that NLCs are very unlikely to occur at latitudes below 50 degrees N during daytime. This conclusion can be made from a tidal temperature mode with cold temperatures during nighttime and temperatures above the limit for NLC occurrence during daytime. The best time for observing mid-latitude NLCs is during the early morning hours.
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| 7. |
- Lyttkens, Carl Hampus, et al.
(författare)
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Coping with Chronic Warfare : The Athenian Experience
- 2022
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Ingår i: Democracy and Salamis : 2500 Years After the Battle That Saved Greece and the Western World - 2500 Years After the Battle That Saved Greece and the Western World. - Cham : Springer International Publishing. - 9783030984311 - 9783030984304 ; , s. 181-200
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In Classical Athens, being at war was more common than peace. The military expenditures were correspondingly large. The main puzzle, however, is not financial, but where the Athenians found the multitude of rowers needed for their ships. It was not until the end of the Peloponnesian War that there were good reasons to use slaves as rowers. The Spartan occupation of Decelea in 413 BCE had profound effects on Athens by forcing more than 20,000 Athenian households (including slaves) to seek protection behind the city walls. This arguably led to the introduction of social support in Athens and an extended use of slaves as rowers. The manpower losses in connection with the naval conflicts must have had a significant impact on Athenian society in several ways. We discuss three cases: the switch from ostracism to the graphe paranomon, the law on citizenship under Pericles, and the decision of the Athenian Assembly to execute the victorious generals after the battle at Arginoussai.
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| 8. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:19, s. 10294-10304
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Tidskriftsartikel (refereegranskat)abstract
- Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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