Bakiri L.,Genes Development and Disease Group |
MacHo-Maschler S.,University of Veterinary Medicine Vienna |
Custic I.,Research Institute of Molecular Pathology |
Custic I.,Hamburg Unit |
And 9 more authors.
Cell Death and Differentiation | Year: 2015
Epithelial-to-mesenchymal transition (EMT) is essential for embryonic morphogenesis and wound healing and critical for tumour cell invasion and dissemination. The AP-1 transcription factor Fra-1 has been implicated in tumorigenesis and in tumour-associated EMT in human breast cancer. We observed a significant inverse correlation between Fra-1 mRNA expression and distant-metastasis-free survival in a large cohort of breast cancer patients derived from multiple array data sets. This unique correlation among Fos genes prompted us to assess the evolutionary conservation between Fra-1 functions in EMT of human and mouse cells. Ectopic expression of Fra-1 in fully polarized, non-tumourigenic, mouse mammary epithelial EpH4 cells induced a mesenchymal phenotype, characterized by a loss of epithelial and gain of mesenchymal markers. Proliferation, motility and invasiveness were also increased in the resulting EpFra1 cells, and the cells were tumourigenic and efficiently colonized the lung upon transplantation. Molecular analyses revealed increased expression of Tgfβ1 and the EMT-inducing transcription factors Zeb1, Zeb2 and Slug. Mechanistically, Fra-1 binds to the tgfb1 and zeb2 promoters and to an evolutionarily conserved region in the first intron of zeb1. Furthermore, increased activity of a zeb2 promoter reporter was detected in EpFra1 cells and shown to depend on AP-1-binding sites. Inhibiting TGFβ signalling in EpFra1 cells moderately increased the expression of epithelial markers, whereas silencing of zeb1 or zeb2 restored the epithelial phenotype and decreased migration in vitro and tumorigenesis in vivo. Thus Fra-1 induces changes in the expression of genes encoding EMT-related transcription factors leading to the acquisition of mesenchymal, invasive and tumorigenic capacities by epithelial cells. This study defines a novel function of Fra-1/AP-1 in modulating tgfb1, zeb1 and zeb2 expression through direct binding to genomic regulatory regions, which establishes a basis for future in vivo genetic manipulations and preclinical studies using mouse models. © 2015 Macmillan Publishers Limited.
Bajrektarevic A.,IMC University of Applied Sciences in Krems
E-Learning and Digital Media | Year: 2013
From Rio to Rio with Kyoto, Copenhagen and Durban in between, the conclusion remains the same: we fundamentally disagree on realities of this planet and the ways we can address them. A decisive breakthrough would necessitate both wider contexts and a larger participatory base so as to identify problems, formulate policies, and broaden and synchronise our actions. Luminaries from the world of science, philosophy, religion, culture and sports are invited too. But, they - as usual - will stuff side-events panels, while only politics will make decisions. Who in politics is sincerely motivated for the long-range policies? This does not pay off politically as such policies are often too complex and too time-consuming to survive the frequency and span of national elections as well as the taste or comprehension of the median voter. Our crisis is not environmental, financial or politico-economic. Deep and structural, this is a crisis of thought, of courage, of our ideas, all which runs us into a deep moral recession. Therefore, very little headway will be made at the Rio Summit.
Bajrektarevic A.,IMC University of Applied Sciences in Krems
E-Learning and Digital Media | Year: 2012
Misled by a quick triumphalism of the social media, the international news agencies have confused the two: revolt and revolution. The past episodes of unrest started as a social, not a political, public revolt. Through the pain of sobriety, the protesters are learning that neither globalisation nor the McFB way of life is a shortcut to development; that free trade is not a virtue, but an instrument; that liberalism is not a state of mind but a well-doctrinated ideology; and, finally, that the social media networks are only a communication tool, not a replacement for independent critical thinking or for the collapsed cross-generational contract. Londoners, Greeks and New Yorkers are experiencing the same thing. How does the 'Arab Spring' correlate with the European Euro-frost, and with American Occupy Wall Street unrest? For almost ten years now, the youth in Europe has been repeatedly sending us a powerful message about the perceived collapse of the social contract. The cross-generational contract should be neither neglected nor built on the over-consumerist, disheartened and egotistic McFB way of life. Equally alienating and dangerously inflammatory is the collision of the entering youth generation (if/when deprived of the opportunity and handed over a lame hope) - through a religious or political radicalisation. In this world spanning Kantian hopes and Hobbesian fears, thus, the final question is: Is there life after FB? If so, how can we register our future claims?
Ignjatovic V.,Murdoch Childrens Research Institute |
Ignjatovic V.,University of Melbourne |
Straka E.,IMC University of Applied Sciences in Krems |
Summerhayes R.,Murdoch Childrens Research Institute |
And 3 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010
Background: Clinically significant age-related differences in the anticoagulation effect of heparin have previously been established in vitro as well as in different clinical settings in vivo. These differences were hypothesized to be due to the age-specific differences in binding of heparin to plasma proteins. Objectives: The aim of this project was to investigate global age-related differences in heparin binding to plasma proteins. Patients/Methods: Heparin-binding proteins were identified by incubating heparin-coated magnetic beads with plasma samples from neonates, children and adults, and purifying the proteins that were bound to the beads in this reaction system. Results: These results provide the first preliminary evidence of age-related differences in the total number and concentration of proteins bound to heparin. The results also suggest, for the first time, that there are age-related differences of heparin binding to antithrombin and thrombin. Conclusions: The results of this study, although preliminary, support and contribute to the explanation of the mechanism of age-related differences in the effect of heparin observed previously in vitro and in vivo. © 2010 International Society on Thrombosis and Haemostasis.
Fernandez-Muinos T.,Tissue Engineering Laboratory |
Suarez-Munoz M.,Tissue Engineering Laboratory |
Suarez-Munoz M.,IMC University of Applied Sciences in Krems |
Sanmarti-Espinal M.,Tissue Engineering Laboratory |
Semino C.E.,Tissue Engineering Laboratory
Tissue Engineering - Part A | Year: 2014
Experimental models for cartilage and bone development have been studied in order to understand the biomechanical and biological parameters that regulate skeletal tissue formation. We have previously described that when mouse embryonic fibroblasts (MEFs) were cultured in a three-dimensional (3D)-soft self-assembling peptide nanofiber, the system engaged in a spontaneous process of cartilage-like formation evidenced by the expression of Sox9, Collagen type II, and proteoglycans. In the present work, we studied the influence that matrix mechanical properties have in modulating lineage commitment in an in vitro model of chondrogenesis. This effect was observed only when MEFs were cultured at low elastic modulus values (∼0.1kPa). Interestingly, under these conditions, the system expressed the chondrogenic inductor BMP4 and its antagonist Noggin. On the other hand, at higher elastic modulus values (∼5kPa), the system expressed Noggin but not BMP4, and did not engage in chondrogenesis, which suggest that the balance between bone morphogenetic protein/Noggin could be implicated in the chondrogenic process. Finally, no evidence of hypertrophy was detected under the conditions tested (by assessing expression of Collagen type X and Runx2) unless we challenged the system by co-culturing it with endothelial cells. Importantly, under these new conditions, the system underwent spontaneous matrix calcium mineralization. These results suggest that the 3D-system described here is sensitive to respond to environmental changes such as biomechanical and biological cues. © 2014, Mary Ann Liebert, Inc. 2014.