Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and their loss has been correlated with poor prognosis in human cancer. Mutational activation of protein kinases and loss of cell adhesion occur together in human lung adenocarcinoma but how these two pathways interconnect is only poorly understood. Mouse models of human lung adenocarcinoma with oncogene expression targeted to subtypes of lung epithelial cells led to formation of adenomas or adenocarcinomas that lacked metastatic potential. Conditional genetic abrogation of epithelial tumour cell adhesion in mice with benign lung tumours induced by oncogenic RAF kinase has been demonstrated to induce intratumourous vascularization (angiogenic switch), progression to invasive adenocarcinoma and micrometastasis. Importantly, breaking cell adhesion in benign oncogene-driven lung tumour cells activated β-catenin signalling and induced the expression of several genes that are normally expressed in intestine rather than the lung. I will discuss potential routes to nuclear β-catenin signalling in cancer and how nuclear β-catenin may epigenetically alter the plasticity of tumour cells during malignant progression

Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution

Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fi.sh Xiphophorus, with the mammalian homlogues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purifi.ed recombinant BDNF. However, the activity ofrecombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng,lml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF bad reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates ftom a common ancestral gene about 600 million years ago. By RNA gel blot anaJysis NGF mRNA was detected during late embryonie development; BDNF was present in adult brain

Öffentlichkeitsmobilisierung und partizipative Demokratie: der österreichische (grüne) Gentechnikkonflikt

'Der vorliegende Artikel strebt einen Diskursbeitrag zum Thema partizipative Demokratie - Öffentlichkeit und politische Partizipation an. Hinterfragt wird, ob auf Öffentlichkeitsmobilisierung basierende politische Partizipation durch zivilgesellschaftliche Akteure prinzipiell als Stärkung partizipativer Demokratie gewertet werden kann. Zur Adressierung dieser Fragestellung wird der öffentliche Konflikt um gentechnisch veränderte Organismen (GVOs) in Österreich analysiert. Die Analyse zeigt, dass öffentliche Mobilisierungen dieses Typus zur Öffnung des politischen Systems gegenüber Akteuren und Themen von 'außerhalb' beitragen können, jedoch auch die Gefahr in sich tragen, dass diese Öffnung einen exklusiven Charakter aufweist - einigen wenigen Akteuren vorbehalten bleibt.' (Autorenreferat)'The article aims to contribute to the scientific discourse on the topic of participative democracy - public space and political participation. The author challenges the perception that political participation by civil society actors based on public mobilisation can be judged in principal as the fortification of participative democracy. By addressing this issue, the public conflict on genetically modified organisms (GMOs) in Austria will be analysed. The analysis shows that public mobilisations of this type can contribute to the opening of the political systems for actors from 'outside', but also that this 'opening' risks to remain exclusive for the majority of actors.' (author's abstract

Expression of B-RAF V600E in Type II Pneumocytes Causes Abnormalities in Alveolar Formation, Airspace Enlargement and Tumor Formation in Mice

Growth factor induced signaling cascades are key regulatory elements in tissue development, maintenance and regeneration. Perturbations of these cascades have severe consequences, leading to developmental disorders and neoplastic diseases. As a major function in signal transduction, activating mutations in RAF family kinases are the cause of human tumorigenesis, where B-RAF V600E has been identified as the prevalent mutant. In order to address the oncogenic function of B-RAF V600E, we have generated transgenic mice expressing the activated oncogene specifically in lung alveolar epithelial type II cells. Constitutive expression of B-RAF V600E caused abnormalities in alveolar epithelium formation that led to airspace enlargements. These lung lesions showed signs of tissue remodeling and were often associated with chronic inflammation and low incidence of lung tumors. The inflammatory cell infiltration did not precede the formation of the lung lesions but was rather accompanied with late tumor development. These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation

Charakteristika der staatlichen Einbindung von Eliten und Bevölkerung in Ideokratien

"This paper shows that ideocracies, especially communist ideocracies, have a specific pattern of cooptation and incorporation of elites and ordinary citizens, which is different from all other political regime types. Ideocracies dominate society through and through by a net of measures that make the citizens materially dependent on the state, from which the individual citizen cannot escape. The strong concentration of the distribution of goods and positions in the hands of the ideocratic state goes hand in glove with the great power to repress non - co - opted people. However, there are trade - offs in the ideocratic pattern of cooptation. The tendency of ideocracies to infantilize its citizens, may provoke reluctance even among otherwise politically indifferent citizens. Nevertheless, despite the trade - offs, the specific pattern of cooptation and incorporation of citizens and elites might help to explain why communist ideocracies were very durable in comparison to other types of political regimes." (author's abstract

Notwendigkeit und "Funktion" der Bildungs- und Berufsberatung. Ein Standpunkt aus arbeitsmarktpolitischer Sicht

Kann die Bildungs- und Berufsberatung einen Beitrag zur Adressierung der zunehmend problematischen Übergänge von der Ausbildung in den Beruf leisten? Kann sie dem vermehrten Bedarf an Begleitung angesichts des so genannten „Active Ageing-Konzepts“ und des „Flexicurity-Ansatzes“ nachkommen? Diesen Fragen widmet sich der vorliegende, eine arbeitsmarktpolitische Sichtweise vertretende Standpunkt, der durch eine Diskussion der Bildungs- und Berufsberatung im „aktivierenden Sozialinvestitionsstaat“ abgerundet wird. Der Autor kommt zu dem Schluss: „Angebote der Bildungs- und Berufsberatung leisten über die Stärkung der individuellen Orientierungs- und Entscheidungsfähigkeit einen wichtigen Beitrag zum erfolgreichen Selbstmanagement.“ (DIPF/Orig.

Bildungs- und Berufsberatung für ImmigrantInnen: Herausforderungen, Reflexionen und Ansätze. Ein kommentierter Tagungsbericht

Bipolare Bildungsmuster der ImmigrantInnen und verstärkte Zuwanderung von Jugendlichen konfrontieren die Bildungs- und Berufsberatung mit vielschichtigen Herausforderungen. Der vorliegende Beitrag stellt innovative Methoden und Ansätze der Adressierung dieser Herausforderungen vor, berichtet über Reflexionen von BeraterInnen zum Thema „Bildungs- und Berufsberatung für ImmigrantInnen“ und schließt mit einer Auswahl politischer Handlungsempfehlungen. (DIPF/Orig.

Editorial

Der Bedarf an Orientierungsangeboten steigt – auch zu Fragen der Bildung und des Berufs. Wie aber sieht Bildungs- und Berufsberatung in Österreich aus? Wie ist sie organisiert und was gehört alles dazu? Was tun Bildungs- und BerufsberaterInnen und was wird ihnen abverlangt? Wie sind sie untereinander vernetzt und vor welchen Herausforderungen stehen sie? Die vorliegende Ausgabe des „Magazin erwachsenenbildung.at“ (Meb) bietet eine Fülle an theoretischen Abhandlungen, empirischen Studien und Praxisberichten, die eine Standortbestimmung der Bildungs- und Berufsberatung in Österreich erlauben. Dabei werden eine europäische und auch eine historische Perspektive eingenommen und werden Professionalisierungsdiskussionen geführt, die bis in die Chaosforschung hineinreichen. Die Beiträge aus der Praxis spannen den Bogen von aktuellen Forschungs- und Entwicklungsergebnissen (Studierendenberatung, aufsuchende, mobile und niederschwellige Bildungsberatung) über Erfahrungsberichte aus der Beratungspraxis (Beratung in der Erstsprache, Vernetzungspraxis) hin zu internationalen Beispielen und Standards (Online-Beratung in Dänemark, Europäische Kompetenzstandards für Bildungs- und Berufsberatung). (DIPF/Orig.)The need for orientation offerings is increasing as are questions of education and career. What is lifelong guidance like in Austria? How is it organized and what is included in it? What do lifelong guidance counsellors do and what is asked of them? How are they networked with one another and what challenges do they face? This edition of the Austrian Open Access Journal on Adult Education (Magazin erwachsenenbildung.at – Meb in German) offers a wealth of theoretical articles, empirical studies and reports on practice that permit an evaluation of the status quo of lifelong guidance in Austria. A European as well as historical perspective is taken and discussions of professionalization are conducted that extend to chaos research. The articles on practice range from current findings from research and development (academic advising; visiting, mobile and drop-in lifelong guidance) to progress reports on the practice of counselling (counselling in the first language, networking practice) to international examples and standards (online counselling in Denmark, European competence standards for lifelong guidance). (DIPF/Orig.

Cooperation of Tyrosine Kinase Receptor TrkB and Epidermal Growth Factor Receptor Signaling Enhances Migration and Dispersal of Lung Tumor Cells

TrkB mediates the effects of brain-derived neurotrophic factor (BDNF) in neuronal and nonnneuronal cells. Based on recent reports that TrkB can also be transactivated through epidermal growth-factor receptor (EGFR) signaling and thus regulates migration of early neurons, we investigated the role of TrkB in migration of lung tumor cells. Early metastasis remains a major challenge in the clinical management of non-small cell lung cancer (NSCLC). TrkB receptor signaling is associated with metastasis and poor patient prognosis in NSCLC. Expression of this receptor in A549 cells and in another adenocarcinoma cell line, NCI-H441, promoted enhanced migratory capacity in wound healing assays in the presence of the TrkB ligand BDNF. Furthermore, TrkB expression in A549 cells potentiated the stimulatory effect of EGF in wound healing and in Boyden chamber migration experiments. Consistent with a potential loss of cell polarity upon TrkB expression, cell dispersal and de-clustering was induced in A549 cells independently of exogeneous BDNF. Morphological transformation involved extensive cytoskeletal changes, reduced E-cadherin expression and suppression of E-cadherin expression on the cell surface in TrkB expressing tumor cells. This function depended on MEK and Akt kinase activity but was independent of Src. These data indicate that TrkB expression in lung adenoma cells is an early step in tumor cell dissemination, and thus could represent a target for therapy development