Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A

Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future

First high-resolution BrO column retrievals from TROPOMI

For more than 2 decades, satellite observations from instruments such as GOME, SCIAMACHY, GOME-2, and OMI have been used for the monitoring of bromine monoxide (BrO) distributions on global and regional scales. In October 2017, the TROPOspheric Monitoring Instrument (TROPOMI) was launched on board the Copernicus Sentinel-5 Precursor platform with the goal of continuous daily global trace gas observations with unprecedented spatial resolution. In this study, sensitivity tests were performed to find an optimal wavelength range for TROPOMI BrO retrievals under various measurement conditions. From these sensitivity tests, a wavelength range for TROPOMI BrO retrievals was determined and global data for April 2018 as well as for several case studies were retrieved. Comparison with GOME-2 and OMI BrO retrievals shows good consistency and low scatter of the columns. The examples of individual TROPOMI overpasses show that due to the better signal-to-noise ratio and finer spatial resolution of 3.5×7&thinsp;km2, TROPOMI BrO retrievals provide good data quality with low fitting errors and unique information on small-scale variabilities in various BrO source regions such as Arctic sea ice, salt marshes, and volcanoes.</p

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Magnetic Anisotropy and Relaxation of Pseudotetrahedral [N2O2] Bis Chelate Cobalt II Single Ion Magnets Controlled by Dihedral Twist Through Solvomorphism

The methanol solvomorph 1 amp; 8201; amp; 8901; amp; 8201;2MeOH of the cobalt II complex [Co LSal,2 amp; 8722;Ph 2] 1 with the sterically demanding Schiff base ligand 2 [1,1 amp; 8242; biphenyl] 2 ylimino methyl phenol HLSal,2 amp; 8722;Ph shows the thus far largest dihedral twist distortion between the two chelate planes compared to an ideal pseudotetrahedral arrangement. The cobalt II ion in 1 amp; 8201; amp; 8901; amp; 8201;2MeOH exhibits an easy axis anisotropy leading to a spin reversal barrier of 55.3 amp; 8197;cm amp; 8722;1, which corresponds to an increase of about 17 amp; 8201; induced by the larger dihedral twist compared to the solvent free complex 1. The magnetic relaxation for 1 amp; 8201; amp; 8901; amp; 8201;2MeOH is significantly slower compared to 1. An in depth frequency domain Fourier transform FD FT THz EPR study not only allowed the direct measurement of the magnetic transition between the two lowest Kramers doublets for the cobalt II complexes, but also revealed the presence of spin phonon coupling. Interestingly, a similar dihedral twist correlation is also observed for a second pair of cobalt II based solvomorphs, which could be benchmarked by FD FT THz EP

Upgrade verification note for the CAMS real-time global atmospheric composition service: Evaluation of the e-suite for the CAMS 47R1 upgrade of October 2020

This report reports on the evaluation of the upgrade of the CAMS global system of October 2020. Before each upgrade, the new model and assimilation configuration is operated in parallel (the e-suite) to the operational real-time service (the o-suite) for about half a year. In the report a set of quick-look validation results are presented from a comparison of the performance of the e-suite runs with the operational o-suite and independent observations. The main conclusions are listed, and the evidence for these findings is presented in the form of a series of plots comparing e-suite, o-suite and independent observations

Upgrade verification note for the CAMS real-time global atmospheric composition service Evaluation of the e-suite for the CAMS upgrade of July 2019; e-suite experiments h4x1, h4xd (2017); e-suite run January-May 2019

This report reports on the evaluation of the upgrade of the CAMS global system of July 2019. Before each upgrade, the new model and assimilation configuration is operated in parallel (the e-suite)to the operational real-time service (the o-suite) for about half a year. In the report a set of quick-look validation results are presented from a comparison of the performance of the e-suite runs with the operational o-suite and independent observations. The main conclusions are listed, and the evidence for these findings is presented in the form of a series of plots comparing e-suite, o-suite and independent observations