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- Marien, E., et al.
(författare)
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Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1539-1548
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Tidskriftsartikel (refereegranskat)abstract
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.
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- Charette, M, et al.
(författare)
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Coastal ocean and shelf-sea biogeochemical cycling of trace elements and isotopes: lessons learned from GEOTRACES
- 2016
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Ingår i: Philosopical Transactions of the Royal Society A. - : The Royal Society. - 1364-503X. ; 374:2081
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Forskningsöversikt (refereegranskat)abstract
- Continental shelves and shelf seas play a central role in the global carbon cycle. However,their importance with respect to trace element and isotope (TEI) inputs to ocean basinsis less well understood. Here, we present major findings on shelf TEI biogeochemistryfrom the GEOTRACES programme as well as a proof of concept for a new method toestimate shelf TEI fluxes. The case studies focus on advances in our understanding of TEIcycling in the Arctic, transformations within a major river estuary (Amazon), shelf sedimentmicronutrient fluxes and basin-scale estimates of submarine groundwater discharge. Theproposed shelf flux tracer is 228-radium (T1/2 =5.75 yr), which is continuously supplied tothe shelf from coastal aquifers, sediment porewater exchange and rivers. Model-derived shelf228Ra fluxes are combined with TEI/ 228Ra ratios to quantify ocean TEI fluxes from thewestern North Atlantic margin. The results from this new approach agree well with previousestimates for shelf Co, Fe, Mn and Zn inputs and exceed published estimates of atmosphericdeposition by factors of approximately 3–23. Lastly, recommendations are made for additionalGEOTRACES process studies and coastal margin-focused section cruises that will help refinethe model and provide better insight on the mechanisms driving shelf-derived TEI fluxesto the ocean.This article is part of the themed issue ‘Biological and climatic impacts of ocean trace elementchemistry’.
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- Fripiat, F., et al.
(författare)
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Influence of the bordering shelves on nutrient distribution in the Arctic halocline inferred from water column nitrate isotopes
- 2018
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Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 63:5, s. 2154-2170
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Tidskriftsartikel (refereegranskat)abstract
- The East Siberian Sea and contiguous western Arctic Ocean basin are characterized by a subsurface nutrient maximum in the halocline, generally attributed to both Pacific inflow and intensive remineralization in shelf bottom waters that are advected into the central basin. We report nitrogen and oxygen isotopic measurement of nitrate from the East Siberian Sea and western Eurasian Basin, in order to gain insight into how nitrate is processed by the microbial community and redistributed in the Arctic Ocean. A large decoupling between nitrate delta N-15 and delta O-18 is reported, increasing and decreasing upward from the Atlantic temperature maximum layer toward the surface, respectively. A correlation between water and nitrate delta O-18 indicates that most of the nitrate (> 60%) at the halocline has been regenerated within the Arctic Ocean. The increase in nitrate delta N-15 correlates with the fixed N deficit, indicating a causal link between the loss of fixed N and the delta N-15 enrichment. This suggests that a significant share of benthic denitrification is driven by nitrate supplied by remineralization and partial nitrification, allowing residual delta N-15-enriched ammonium to diffuse out of the sediments. By increasing nutrient concentrations and fixed N deficit in shelf bottom waters, this imprint is attenuated offshore following advection into the halocline by nitrate regeneration and mixing. Estimation of the sedimentary isotope effect related to benthic denitrification yields values in the range of 2.4-3.8 parts per thousand, with its magnitude driven by both the degree of coupling between remineralization and nitrification, and fixed N concentrations in shelf bottom waters.
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