| 1. |
- Andersen, T. C. B., et al.
(författare)
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The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell?specific adapter protein
- 2019
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 294:42, s. 15480-15494
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Tidskriftsartikel (refereegranskat)abstract
- T-cell activation requires stimulation of specific intracellular signaling pathways in which protein-tyrosine kinases, phosphatases, and adapter proteins interact to transmit signals from the T-cell receptor to the nucleus. Interactions of LCK proto-oncogene, SRC family tyrosine kinase (LCK), and the IL-2?inducible T cell kinase (ITK) with the T cell-specific adapter protein (TSAD) promotes LCK-mediated phosphorylation and thereby ITK activation. Both ITK and LCK interact with TSAD's proline-rich region (PRR) through their Src homology 3 (SH3) domains. Whereas LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3 domain. To begin to understand on a molecular level how the LCK SH3 and ITK SH3 domains interact with TSAD in human HEK293T cells, here we combined biochemical analyses with NMR spectroscopy. We found that the ITK and LCK SH3 domains potentially have adjacent and overlapping binding sites within the TSAD PRR amino acids (aa) 239?274. Pulldown experiments and NMR spectroscopy revealed that both domains may bind to TSAD aa 239?256 and aa 257?274. Co-immunoprecipitation experiments further revealed that both domains may also bind simultaneously to TSAD aa 242?268. Accordingly, NMR spectroscopy indicated that the SH3 domains may compete for these two adjacent binding sites. We propose that once the associations of ITK and LCK with TSAD promote the ITK and LCK interaction, the interactions among TSAD, ITK, and LCK are dynamically altered by ITK phosphorylation status.
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| 2. |
- Mazzola, F., et al.
(författare)
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Graphene coatings for chemotherapy: avoiding silver-mediated degradation
- 2015
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Ingår i: 2d Materials. - : IOP Publishing. - 2053-1583. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy treatment usually involves the delivery of fluorouracil (5-Fu) together with other drugs through central venous catheters. Catheters and their connectors are increasingly treated with silver or argentic alloys/compounds. Complications arising from broken catheters are common, leading to additional suffering for patients and increased medical costs. Here, we uncover a likely cause of such failure through a study of the surface chemistry relevant to chemotherapy drug delivery, i.e. between 5-Fu and silver. We show that silver catalytically decomposes 5-Fu, compromising the efficacy of the chemotherapy treatment. Furthermore, HF is released as a product, which will be damaging to both patient and catheter. We demonstrate that graphene surfaces inhibit this undesirable reaction and would offer superior performance as nanoscale coatings in cancer treatment applications.
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| 3. |
- Kjelstrup, S., et al.
(författare)
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A thermodynamic metric for assessing sustainable use of natural resources
- 2015
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Ingår i: International Journal of Applied Thermodynamics. - : International Centre for Applied Thermodynamics (ICAT). - 1301-9724 .- 2146-1511. ; 18:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- A thermodynamic metric is proposed to supplement existing scales in the assessment of the way we use our natural resources. This metric has the advantage of being absolute and independent of economy, suitable for comparison of technologies, and can be used at molecular level as well as process-units and systems levels. It measures loss of useful work (exergy) in cradle-to-grave or complete recycling systems in terms of generalized friction or entropy production and may deliver realistic targets for process operations. This absolute scale can be useful also for international legislation and to foster a development in direction of more sustainable technologies. In an extended perspective, the presented approach may form a universal basis for analysis and development of national economies and policies regarding industry, engineering and environment. This may give new opportunities to put political resource discussions on a solid objective footing.
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