Investigating the regulation of fos during embryonic wound healing and morphogenesis in Xenopus

Extracellular signal-related kinase (ERK) regulates gene expression through substrate phosphorylation. The conserved transcriptional repressor Capicua (CIC) is negatively regulated via ERK-mediated phosphorylation. Both fibroblast growth factor (FGF) signalling and embryonic wounding activate ERK, however the contribution of CIC to transcriptional regulation in these contexts is understudied. It was hypothesised that ERK relieves CIC-mediated repression downstream of FGF signalling and post-wounding during Xenopus development; this project aimed to identify targets of CIC/FGF and investigate their regulation in these contexts. Here, 44 putative CIC/FGF target genes, including the AP-1 gene fos, were identified through gene-level differential expression analysis of RNA-seq data from FGF4 overexpressing and CIC knockdown X. tropicalis embryos. Xenopus embryos were treated with FGF (SU5402), MEK (PD0325901) or nitric oxide (NO) synthase (TRIM) chemical inhibitors and the expression of fos and activated ERK investigated via in situ hybridisation and immunostaining, respectively. Gastrula stage expression of fos was found to be FGF-dependent, and CIC binding motifs were identified within a conserved region of fos intron 1. Corroborating with CIC/ERK-mediated regulation, fos expression was reduced following ERK inhibition during embryonic wound healing. Inhibiting NO production elevated activated ERK expression post-wounding, thus NO may negatively regulate fos expression via ERK. Inhibiting ERK activation similarly reduced fos expression during neurulation, suggesting comparable mechanisms may govern wound healing and morphogenesis. Other CIC targets representing AP-1 genes, namely jun and atf3, were also found to be expressed post-wounding and during neurulation. Overall therefore, the data support the hypothesis, and propose a novel role for CIC in intron mediated enhancement of the CIC/FGF target gene fos, and a wider role for CIC in regulating AP-1 gene expression during wound healing and morphogenesis

Gender and class in Britain and France

This article examines the treatment of women's oppression in feminist theory, focusing on the engagement of second wave feminists with the concept of class and its relation to gender. This examination is carried out with reference to British and French feminisms, identifying the main trends and shifts that have developed over the last 35 years and noting that while these are undoubtedly influenced by a particular national context they are also shaped by increasing European integration and social, political and cultural exchanges at a global level. The authors find evidence of a number of similarities in the questions that feminist theorists have asked in Britain and France but also demonstrate that there are significant differences. They conclude that areas of convergent theoretical interests will extend along with cross-border flows of peoples and information

Activating transcription factor 3 is a positive regulator of human IFNG gene expression

IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-α in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-α, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4+ Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-α, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4+ T cells enhanced the production of IFN-α, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-γ production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4+ T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation

Regulation of gene expression downstream of a novel Fgf/Erk pathway during Xenopus development

Activation of Map kinase/Erk signalling downstream of fibroblast growth factor (Fgf) tyrosine kinase receptors regulates gene expression required for mesoderm induction and patterning of the anteroposterior axis during Xenopus development. We have proposed that a subset of Fgf target genes are activated in the embyo in response to inhibition of a transcriptional repressor. Here we investigate the hypothesis that Cic (Capicua), which was originally identified as a transcriptional repressor negatively regulated by receptor tyrosine kinase/Erk signalling in Drosophila, is involved in regulating Fgf target gene expression in Xenopus. We characterise Xenopus Cic and show that it is widely expressed in the embryo. Fgf overexpression or ectodermal wounding, both of which potently activate Erk, reduce Cic protein levels in embryonic cells. In keeping with our hypothesis, we show that Cic knockdown and Fgf overexpression have overlapping effects on embryo development and gene expression. Transcriptomic analysis identifies a cohort of genes that are up-regulated by Fgf overexpression and Cic knockdown. We investigate two of these genes as putative targets of the proposed Fgf/Erk/Cic axis: fos and rasl11b, which encode a leucine zipper transcription factor and a ras family GTPase, respectively. We identify Cic consensus binding sites in a highly conserved region of intron 1 in the fos gene and Cic sites in the upstream regions of several other Fgf/Cic co-regulated genes, including rasl11b. We show that expression of fos and rasl11b is blocked in the early mesoderm when Fgf and Erk signalling is inhibited. In addition, we show that fos and rasl11b expression is associated with the Fgf independent activation of Erk at the site of ectodermal wounding. Our data support a role for a Fgf/Erk/Cic axis in regulating a subset of Fgf target genes during gastrulation and is suggestive that Erk signalling is involved in regulating Cic target genes at the site of ectodermal wounding

The role of universities in the development of plurilingual repertoires: the voices of non-traditional adult students

The purpose of this paper is to present a study on the non-traditional adult students’ (NTAS) perceptions concerning the role of university in the development of their plurilingual repertoires. Data were collected through biographical interviews with NTAS with fewer and more plurilingual experiences. The results show that NTAS with more plurilingual experiences are more aware of their plurilingual repertoire and acknowledge higher education as an opportunity to further develop it. It also appears that if university promotes a favourable environment for the development of plurilingual repertoires, there may be a change in NTAS’ perception regarding lifelong language learning

Asymmetry, realised volatility and stock return risk estimates

In this paper we estimate minimum capital risk requirements for short and long positions with three investment horizons, using the traditional GARCH model and two other GARCH-type models that incorporate the possibility of asymmetric responses of volatility to price changes. We also address the problem of the extremely high estimated persistence of the GARCH model to generate observed volatility patterns by including realised volatility as an explanatory variable into the model’s variance equation. The results suggest that the inclusion of realised volatility improves the GARCH forecastability as well as its ability to calculate accurate minimum capital risk requirements and makes it quite competitive when compared with asymmetric conditional heteroscedastic models such as the GJR and the EGARCH.info:eu-repo/semantics/publishedVersio