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| 12. |
- Balzarini, J, et al.
(författare)
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Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives
- 1996
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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. ; 93:14, s. 7295-7299
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Tidskriftsartikel (refereegranskat)abstract
- So324 is a 2',3'-dideoxy-2',3'-didehydrothymidine-5'-monophosphate (d4T-MP) prodrug containing at the phosphate moiety a phenyl group and the methylester of alanine linked to the phosphate through a phosphoramidate linkage. So324 has anti-HIV activity in human CEM, MT4, and monocyte/macrophage cells that is superior to that of d4T. In contrast to d4T, So324 is also able to inhibit HIV replication in thymidine kinase-deficient CEM cells. After uptake of So324 by intact human lymphocytes, d4T-MP is released and subsequently converted intracellularly to d4T-TP. In addition, accumulation of substantial amounts of a novel d4T derivative has been found. This d4T metabolite has been characterized as alaninyl d4T-MP. The latter metabolite accumulates at approximately 13- to 200-fold higher levels than d4T-TP depending the experimental conditions. Alaninyl d4T-MP should be considered as an intra- and/or extracellular depot form of d4T and/or d4T-MP. These findings may explain the superior anti-retroviral activity of So324 over d4T in cell culture.
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| 13. |
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| 14. |
- 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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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Vanden Berghe, T, et al.
(författare)
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Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features
- 2010
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Ingår i: CELL DEATH AND DIFFERENTIATION. - : Nature Publishing Group. - 1350-9047 .- 1476-5403. ; 17:6, s. 922-930
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Tidskriftsartikel (refereegranskat)abstract
- Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma membrane and spilling of the intracellular content. Subcellular events during tumor necrosis factor (TNF)-induced necroptosis, H2O2-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy. The cellular disintegration phase of the three types of necrosis is characterized by an identical sequence of subcellular events, including oxidative burst, mitochondrial membrane hyperpolarization, lysosomal membrane permeabilization and plasma membrane permeabilization, although with different kinetics. H2O2-induced necrosis starts immediately by lysosomal permeabilization. In contrast, during TNF-mediated necroptosis and anti-Fas-induced secondary necrosis, this is a late event preceded by a defined signaling phase. TNF-induced necroptosis depends on receptor-interacting protein-1 kinase, mitochondrial complex I and cytosolic phospholipase A(2) activities, whereas H2O2-induced necrosis requires iron-dependent Fenton reactions.
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| 19. |
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