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- Marien, E., et al.
(author)
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Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
- 2015
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1539-1548
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Journal article (peer-reviewed)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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| 3. |
- Bogie, JFJ, et al.
(author)
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Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
- 2020
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:5
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Journal article (peer-reviewed)abstract
- Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
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| 5. |
- Charette, M, et al.
(author)
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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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In: Philosopical Transactions of the Royal Society A. - : The Royal Society. - 1364-503X. ; 374:2081
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Research review (peer-reviewed)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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| 6. |
- Burd, Adrian B., et al.
(author)
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Assessing the Apparent Imbalance Between Geochemical and Biochemical Indicators of Meso- and Bathypelagic Biological Activity: What the @$#! is wrong with present calculations of carbon budgets?
- 2010
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In: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 57:16, s. 1557-1571
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Journal article (peer-reviewed)abstract
- Metabolic activity in the water column below the euphotic zone is ultimately fuelled by the vertical flux of organic material from the surface. Over time, the deep ocean is presumably at steady state, with sources and sinks balanced. But recently compiled global budgets and intensive local field studies suggest that estimates of metabolic activity in the dark ocean exceed the influx of organic substrates. This imbalance indicates either the existence of unaccounted sources of organic carbon or that metabolic activity in the dark ocean is being over-estimated. Budgets of organic carbon flux and metabolic activity in the dark ocean have uncertainties associated with environmental variability, measurement capabilities, conversion parameters, and processes that are not well sampled. We present these issues and quantify associated uncertainties where possible, using a Monte Carlo analysis of a published data set to determine the probability that the imbalance can be explained purely by uncertainties in measurements and conversion factors. A sensitivity analysis demonstrates that the bacterial growth efficiencies and assumed cell carbon contents have the greatest effects on the magnitude of the carbon imbalance. Two poorly quantified sources, lateral advection of particles and a population of slowly settling particles, are discussed as providing a means of closing regional carbon budgets. Finally, we make recommendations concerning future research directions to reduce important uncertainties and allow a better determination of the magnitude and causes of the unbalanced carbon budgets. (C) 2010 Elsevier Ltd. All rights reserved.
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| 7. |
- Fripiat, F., et al.
(author)
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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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In: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 63:5, s. 2154-2170
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Journal article (peer-reviewed)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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| 8. |
- Thomas, H, et al.
(author)
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Barium and carbon fluxes in the Canadian Arctic Archipelago
- 2011
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In: Journal of Geophysical Research - Oceans. - 0148-0227 .- 2156-2202. ; 116
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Journal article (peer-reviewed)abstract
- The seasonal and spatial variability of dissolved Barium (Ba) in the Amundsen Gulf, southeastern Beaufort Sea, was monitored over a full year from September 2007 to September 2008. Dissolved Ba displays a nutrient-type behavior: the maximum water column concentration is located below the surface layer. The highest Ba concentrations are typically observed at river mouths, the lowest concentrations are found in water masses of Atlantic origin. Barium concentrations decrease eastward through the Canadian Arctic Archipelago. Barite (BaSO4) saturation is reached at the maximum dissolved Ba concentrations in the subsurface layer, whereas the rest of the water column is undersaturated. A three end-member mixing model comprising freshwater from sea-ice melt and rivers, as well as upper halocline water, is used to establish their relative contributions to the Ba concentrations in the upper water column of the Amundsen Gulf. Based on water column and riverine Ba contributions, we assess the depletion of dissolved Ba by formation and sinking of biologically bound Ba (bio-Ba), from which we derive an estimate of the carbon export production. In the upper 50 m of the water column of the Amundsen Gulf, riverine Ba accounts for up to 15% of the available dissolved Ba inventory, of which up to 20% is depleted by bio-Ba formation and export. Since riverine inputs and Ba export occur concurrently, the seasonal variability of dissolved Ba in the upper water column is moderate. Assuming a fixed organic carbon to bio-Ba flux ratio, carbon export out of the surface layer is estimated at 1.8 ± 0.45 mol C m−2 yr−1. Finally, we propose a climatological carbon budget for the Amundsen Gulf based on recent literature data and our findings, the latter bridging the surface and subsurface water carbon cycles.
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