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- Ragunathrao, Vijay Avin Balaji, et al.
(author)
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Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling
- 2019
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In: Cell Reports. - : CELL PRESS. - 2211-1247. ; 29:11, s. 3472-3487
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Journal article (peer-reviewed)abstract
- The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in endothelial cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic signaling to enhance tumor growth. We show that cancer cells induce S1 PR1 activity in ECs, and thereby, conditional deletion of Si PR1 in ECs (EC-Slpr1(-/-) mice) impairs tumor vascularization and growth. Mechanistically, we show that S1 PR1 engages the heterotrimeric G-protein Gi, which amplifies VEGF-VEGFR2 signaling due to an increase in the activity of the tyrosine kinase c-Abl1. c-Abl1, by phosphorylating VEGFR2 at tyrosine-951, prolongs VEGFR2 retention on the plasmalemma to sustain Rac1 activity and EC migration. Thus, S1 PR1 or VEGFR2 antagonists, alone or in combination, reverse the tumor growth in control mice to the level seen in EC-Slpr1(-/-) mice. Our findings suggest that blocking S1 PR1 activity in ECs has the potential to suppress tumor growth by preventing amplification of VEGF-VEGFR2 signaling.
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- Goryl, P. P., et al.
(author)
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Tango based control system at SOLARIS Synchrotron
- 2016
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In: IPAC 2016 - Proceedings of the 7th International Particle Accelerator Conference. - 9783954501472 ; , s. 4101-4103
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Conference paper (peer-reviewed)abstract
- A National Synchrotron Radiation Centre SOLARIS has been recently built in Krakow, Poland. The accelera tor is in commissioning phase. The control system is in operation and provides all functionalities required for the commissioning process. The system is based on Tango Controls and has been developed with strong collabora tion with MAX-IV, Lund Sweden and the Tango Commu nity. Protections systems uses Rockwell and Siemens PLC hardware. Synchronization system is based on the MRF hardware. Status, technologies and performance experience will be presented.
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- Zielinski, P., et al.
(author)
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Divergence history of the Carpathian and smooth newts modelled in space and time
- 2016
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In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25:16, s. 3912-3928
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Journal article (peer-reviewed)abstract
- Information about demographic history is essential for the understanding of the processes of divergence and speciation. Patterns of genetic variation within and between closely related species provide insights into the history of their interactions. Here, we investigated historical demography and genetic exchange between the Carpathian (Lissaritan montandoni, Lm) and smooth (L. vulgaris, Lv) newts. We combine an extensive geographical sampling and multilocus nuclear sequence data with the approximate Bayesian computation framework to test alternative scenarios of divergence and reconstruct the temporal and spatial pattern of gene flow between species. A model of recent (last glacial period) interspecific gene flow was favoured over alternative models. Thus, despite the relatively old divergence (4-6 mya) and presumably long periods of isolation, the species have retained the ability to exchange genes. Nevertheless, the low migration rates (ca. 10 per gene copy per generation) are consistent with strong reproductive isolation between the species. Models allowing demographic changes were favoured, suggesting that the effective population sizes of both species at least doubled as divergence reaching the current ca. 0.2 million in Lm and 1 million in Lv. We found asymmetry in rates of interspecific gene flow between Lm and one evolutionary lineage of Lv. We suggest that intraspecific polymorphism for hybrid incompatibilities segregating within Lv could explain this pattern and propose further tests to distinguish between alternative explanations. Our study highlights the importance of incorporating intraspecific genetic structure into the models investigating the history of divergence.
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