Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

More than meets the eye: patterns and shifts in middle school mathematics teachers’ descriptions of models

Modeling is a major topic of interest in mathematics education. However, the field’s definition of models is diverse. Less is known about what teachers identify as mathematical models, even though it is teachers who ultimately enact modeling activities in the classroom. In this study, we asked nine middle school teachers with a variety of academic backgrounds and teaching experience to collect data related to one familiar physical phenomenon, cooling liquid. We then asked each participant to construct a model of that phenomenon, describe why it was a model, and identify whether a variety of artifacts representing the phenomenon also counted as models during a semi-structured interview. We sought to identify: what do mathematics teachers attend to when describing what constitutes a model? And, how do their attentions shift as they engage in different activities related to models? Using content analysis, we documented what features and purposes teachers attended to when describing a mathematical model. When constructing their own model, they focused on the visual form of the model and what quantitative information it should include. When deciding whether particular representational artifacts constituted models, they focused on how the representations reflected the system under study, and what purposes those representations could serve in further understanding that system. These findings suggest teachers may have multiple understandings of models, which are active at different times and reflect different perspectives. This has implications for research, teacher education, and professional development

Meanings Attributed to Letters in Functional Contexts by Primary School Students

This article describes part of the findings of a teaching experiment whose objective is to investigate the algebraic abilities of elementary students when they solve situations that involve a functional relationship. In particular, we focus on describing the use and meanings attributed to letters by third-year primary school students when faced with verbal problems related to the generalisation of a functional relationship. Drawing from the functional approach to early algebra and set in Spain, the study expands on earlier research conducted on primary school students’ use of letters in algebraic contexts. Their initial reactions to the use of letters to represent indeterminate quantities and how those reactions changed in the course of three sessions are described. Analyses of the students’ written answers together with their participation in group discussions yield qualitative data on how students associate the idea of variability with indeterminate quantities and use letters, numbers or both to represent that notion