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

Characterization of a new Bacillus thuringiensis endotoxin, Cry47Aa, from strains that are toxic to the Australian sheep blowfly, Lucilia cuprina

Sixteen isolates of Bacillus thuringiensis, derived from various soil samples collected in Australia, are highly toxic to larvae of the sheep blowfly (Lucilia cuprina). The toxin gene from one of the strains (CAA890) was cloned by genome walking, and sequencing of the cloned fragments revealed a new cry gene, encoding a protein of 1134 amino acid residues, with a theoretical molecular mass of 139,209 Da. Based on the amino acid sequence comparison with known Cry δ-endotoxins, the gene was designated cry47Aa. Homology modelling based on known crystal structures of the Cry toxins reveals the differences to be located in the loops of domain II in the putative toxin-receptor binding surfaces between Cry47Aa and the dipteran active Cry2Aa. We also showed that the cry47Aa gene is present in the other isolates that are highly toxic to the sheep blowfly

SCCS Recommendations and Conference 2013 Executive Summary - Unlocking North Sea CO2 Storage for Europe: Practical actions for the next five years

CARBON dioxide emissions are the major cause of climate change: that is unequivocal. To limit the effects, we must reduce the amount of fossil carbon combusted and emitted as CO . Carbon capture and storage 2 (CCS) is the only technology that directly reduces emissions at source, and enables countries to manage carbon budgets for both power plants and process industries. The next five years will be crucial in putting CCS back into position as an enabler of Europe's transition to a low-carbon economy. Practical actions must be combined with durable policy drivers to rebuild confidence and attract investment. This will be essential for large-scale emissions reductions from both industry and power generation to 2030 and 2050 as Europe seeks to manage climate risk, retain jobs and improve its low-carbon competitiveness. The North Sea is the largest CO2 storage resource in Europe, and offers the ideal location for immediate efforts. By using low-cost available CO2 from industrial sources, Europe can accelerate the development of enabling infrastructures for CO2 transport and storage. The following six recommendations set out steps that can be taken now to help unlock North Sea CO2 storage for Europe.CARBON dioxide emissions are the major cause of climate change: that is unequivocal. To limit the effects, we must reduce the amount of fossil carbon combusted and emitted as CO . Carbon capture and storage 2 (CCS) is the only technology that directly reduces emissions at source, and enables countries to manage carbon budgets for both power plants and process industries. The next five years will be crucial in putting CCS back into position as an enabler of Europe's transition to a low-carbon economy. Practical actions must be combined with durable policy drivers to rebuild confidence and attract investment. This will be essential for large-scale emissions reductions from both industry and power generation to 2030 and 2050 as Europe seeks to manage climate risk, retain jobs and improve its low-carbon competitiveness. The North Sea is the largest CO2 storage resource in Europe, and offers the ideal location for immediate efforts. By using low-cost available CO2 from industrial sources, Europe can accelerate the development of enabling infrastructures for CO2 transport and storage. The following six recommendations set out steps that can be taken now to help unlock North Sea CO2 storage for Europe