The role of GLI2 in human basal cell carcinoma tumourigenesis

PhDAbnormal Sonic Hedgehog (SHH) signalling leads to increased transcriptional activation of its downstream effector, GLI2, which is implicated in the pathogenesis of a variety of human tumours, including human basal cell carcinoma (BCC). However, little is known about the molecular mechanisms underlying the tumourigenic role of GLI2 in human skin keratinocytes. This study examines the effects of inducible and stable expression of constitutively active GLI2 (GLI2:N) oncogenic transcription factor, on immortalised human epidermal keratinocytes. It is shown here that GLI2:N overexpressing N/TERT keratinocytes display gene expression patterns and phenotypic characteristics reminiscent of those observed in human BCC in vivo. It is also shown for first time, that expression of GLI2:N in N/TERT keratinocytes is sufficient to induce accumulation of binucleated/tetraploid cells as evidenced by an increase in G2/M phase of the cell cycle and binucleate cell counting, and to promote polyploidy and aneuploidy, in the absence of increased cell death or apoptosis. This cell cycle deregulation is accompanied by strong activation of anti-apoptotic protein BCL-2 and simultaneous suppression of important cell-cycle regulators such as 14-3-3σ and CDK inhibitor p21WAF1/CIP1, with no change in p53 protein levels, indicating uncontrolled proliferation of cells with ploidy abnormalities and/or DNA damage. Consistently, it is shown that p21WAF1/CIP1 protein is also absent in human BCC tumours and that forced overexpression of GLI2:N renders human keratinocytes resistant to apoptosis mediated by ultraviolet B (UVB, 290-320 nm), one of the most important etiological factors in BCC formation. Karyotype analysis of GLI2:N N/TERT keratinocytes further demonstrates that overexpression of GLI2:N induces numerical (tetraploidy, polyploidy, aneuploidy) and structural instability in N/TERT keratinocytes including chromosomal translocations and double minute chromosomes. Furthermore, β-catenin activation is the most common alteration observed during aberrant WNT signalling, and is often implicated in the development of human carcinogenesis and metastasis. In this study it is shown that GLI2:N induction induces nuclear accumulation of β-catenin in keratinocyte cell culture and in the basal layer of organotypic skin rafts, similar to human BCCs. In addition, several WNT genes were found to be upregulated upon GLI2:N induction, while β-catenin transcriptional activity is increased upon stable and conditional expression of GLI2:N. Overall these data give new insights for the possible mechanisms that mediate the tumourigenic potential of GLI2

Teaching in Multicultural Societies: the theories and practice of teachers in Greek Community Schools

The study focuses on teachers funded by the Greek state to come to the UK and work in Greek Community Schools. It explores their theories and practices as they develop through the experience of working with minority groups, and as they shift in position from Greece to the UK The study is rooted in the assumption that teachers are professionals who reflect on their experiences (often critically) and, as they have to 'translate' policy into workable practice, are in a unique position to contribute to educational research and the policy process. The research 'gives voice' to the teachers, potentially contributing to the policy agenda both in Greece (in the context of its recent attempts to make education more multicultural through an 'Interculturalist' education policy), and in the Community Schools in the UK The research focuses on three sets of questions: those connected with language; questions relating to issues of culture and identity; and questions related to teachers' reflective practice. The processes and conditions which support reflection and critique are explored, for example the role of 'critical incidents' in destabilising preconceptions and assumptions. The study explores and attempts to connect discourses on multiculturalism with discourses on the role of the teacher, through positioning the teacher at the centre of the discourse. The findings indicate that as the teachers become more reflective, their theories become at once more grounded and more critical. Thus a shift takes place towards discourses supporting additive forms of bilingualism, supporting strong critical forms of multiculturalism - and opposing powerful assimilationist discourses. At the same time the 'model' of the teacher revealed in their discourse shifts: from 'deliverer' to active contributor, capable of contributing to the policy process. In sum, the teachers' knowledge of different models of managing multicultural reality represents unique value as feedback to both the Community Schools and the mainstream in Greece

Aprendiendo a verbalizar

Treball Final de Grau en Mestre o Mestra d'Educació Infantil. Codi: MI1040. Curs acadèmic: 2016/2017Then presents the final degree work which deals mainly with the relevance of the stimulation of the oral language in the second cycle of early childhood education. It also aims to reach a clear definition of the theoretical concept of the oral language, through various theories of acquisition anddevelopment. Second, starting from the theoretical framework, has carried out a methodological proposal with the intention of working, from three areas of early childhood education, development and acquisition of the oral language in pupils of 3-4 years, checking, at the same time, the level of acquired language that have depending on their age and the difficulties presented when it comes to express orally. In this way, also contrasts that language is one of the main tools of thought, being the backbone on which are built the rest of learning, as the cited authors. Is a methodology that revolves around 7 activities where function and the attitude of the teacher is more than relevant and, therefore, a conditioning factor for the students. The results show us if raised activities are suited to this role, commenting on the conclusions, the singularities of each activity section.A continuación, se expone el Trabajo Final de Grado que aborda, principalmente, la relevancia de la estimulación del lenguaje oral en el segundo ciclo de Educación Infantil. También pretende acercarse a una clara definición del concepto teórico del lenguaje oral, a través de diversas teorías de adquisición y de desarrollo del mismo. En segundo lugar, a partir del marco teórico, se ha llevado a cabo una propuesta metodológica con la intención de trabajar, desde las tres áreas de la educación infantil, el desarrollo y adquisición de la lengua oral en alumnos de 3-4 años, comprobando, a su vez, el nivel de lenguaje adquirido que tienen en función de su edad y las dificultades que presentan a la hora de expresarse oralmente. De este modo, también se contrasta que el lenguaje es una de las principales herramientas del pensamiento, siendo el eje vertebrador sobre el que se han de construir el resto de aprendizajes, como afirman los autores citados. Es una propuesta metodológica que gira en torno a 7 actividades donde la función y la actitud del maestro es más que relevante y, por lo tanto, un condicionante para los alumnos. Los resultados obtenidos nos muestran si las actividades planteadas son las adecuadas para cumplir este cometido, comentando en el apartado de conclusiones, las singularidades de cada actividad

On Rank Problems for Planar Webs and Projective Structures

We present old and recent results on rank problems and linearizability of geodesic planar webs.Comment: 31 pages; LaTeX; corrected the abstract and Introduction; added reference

Phase portraits of separable Hamiltonian systems

We study some generalizations of potential Hamiltonian systems (H(x, y) = y 2 + F(x)) with one degree of freedom. In particular, we are interested in Hamiltonian systems with Hamiltonian functions of type H(x, y) = F(x) + G(y) arising in applied mechanical problems. We present an algorithm to plot the phase portrait (include the behavior at infinity) of any Hamiltonian system of type H(x, y) = F(x) +G(y), where F and G are arbitrary polynomials. We are able to give the full description in the Poincaré disk according to the graphs of F and G, extending the well-known method for the “finite”phase portrait of potential systems