Myofibroblast transdifferentiation is associated with changes in cellular and extracellular vesicle miRNA abundance

Transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic tumour-derived factor promotes fibroblast differentiation in the tumour microenvironment and is thought to contribute to the development of pro-tumourigenic cancer-associated fibroblasts (CAFs) by promoting myofibroblast differentiation. miRNA dysregulation has been demonstrated in myofibroblast transdifferentiation and CAF activation, however, their expression varies among cell types and with the method of fibroblast induction. Here, the expression profile of miRNA in human primary oral fibroblasts treated with TGF-β1, to derive a myofibroblastic, CAF-like phenotype, was determined compared to untreated fibroblasts. Myofibroblast transdifferentiation was determined by the expression of alpha-smooth muscle actin (α-SMA) and fibronectin-1 extra domain A (FN-EDA1) using quantitative real-time PCR (qRT-PCR) and western blot. The formation of stress fibres was assessed by fluorescence microscopy, and associated changes in contractility were assessed using collagen contraction assays. Extracellular vesicles (EVs) were purified by using size exclusion chromatography and ultracentrifugation and their size and concentration were determined by nanoparticle tracking analysis. miRNA expression profiling in oral fibroblasts treated with TGF-β1 and their extracellular vesicles was carried out using tiling low-density array cards. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform functional and pathway enrichment analysis of target genes. In this study, TGF-β1 induced a myofibroblastic phenotype in normal oral fibroblasts as assessed by expression of molecular markers, the formation of stress fibres and increased contractility. TaqMan Low-Density Array (TLDA) analysis demonstrated that miR-503 and miR-708 were significantly upregulated, while miR-1276 was significantly downregulated in TGF-β1-treated oral fibroblasts (henceforth termed experimentally-derived CAF, eCAF). The gene functional enrichment analysis showed that the candidate miRNAs have the potential to modulate various pathways; including the Ras associated protein 1 (Rap1), PI3K-Akt, and tumour necrosis factor (TNF) signalling pathways. In addition, altered levels of several miRNAs were detected in eCAF EV, including miR-142 and miR-222. No differences in size or abundance of EV were detected between eCAF and normal oral fibroblast (NOF). Little overlap was observed between changes in cellular and EV miRNA profiles, suggesting the possibility of selective loading of EV miRNA. The study reveals miRNA expression signature could be involved in myofibroblast transdifferentiation and the miRNA cargo of their EV, providing novel insight into the involvement of miRNA in CAF development and function

Temperature Dependence of the Dynamics of Portevin-Le Chatelier Effect in Al-2.5%Mg alloy

Tensile tests were carried out by deforming polycrystalline samples of Al-2.5%Mg alloy at four different temperatures in an intermediate strain rate regime of 2x10-4s-1 to 2x10-3s-1. The Portevin-Le Chatelier (PLC) effect was observed throughout the strain rate and temperature region. The mean cumulative stress drop magnitude and the mean reloading time exhibit an increasing trend with temperature which is attributed to the enhanced solute diffusion at higher temperature. The observed stress-time series data were analyzed using the nonlinear dynamical methods. From the analyses, we could establish the presence of deterministic chaos in the PLC effect throughout the temperature regime. The dynamics goes to higher dimension at a sufficiently high temperature of 425K but the complexity of the dynamics is not affected by the temperature.Comment: 18 pages, 8 figures; accepted in Met. Mater. Trans.

Creative methods: problematics for inquiry and pedagogy in health and social care

This article provides an overview of initial discussions emerging from the Creative Methods Network, an informal organisation concerned with the use of the creative arts in research, teaching and practice in health and social care. Key issues are presented and contextualised with regard to the current conditions in which health and social care research and education is practised. Our own discussions have come to question the seeming dominance of governance within professional education programmes in which there is a primary focus on developing technical skill and capacity. Such governance often extends itself to the measurement of the implementation of these technical skills and this is set against concerns about the absence of creativity and the humanities in the educational programmes of caring for human beings. Consequently, the article reflects a view that the use of the creative arts and humanities in the education of the human caring professions is being eroded away in favour of technical-rational reasoning. It is argued that this then presents an important problem manifested in an emphasis on established and quantifiable knowledge transfer which inhibits other forms of knowledge generation. For the purposes of this discussion we have viewed this problem through the lenses offered by Foucault and Bourdieu

In the social factory? Immaterial labour, precariousness and cultural work

This article introduces a special section concerned with precariousness and cultural work. Its aim is to bring into dialogue three bodies of ideas -- the work of the autonomous Marxist 'Italian laboratory'; activist writings about precariousness and precarity; and the emerging empirical scholarship concerned with the distinctive features of cultural work, at a moment when artists, designers and (new) media workers have taken centre stage as a supposed 'creative class' of model entrepreneurs. The paper is divided into three sections. It starts by introducing the ideas of the autonomous Marxist tradition, highlighting arguments about the autonomy of labour, informational capitalism and the 'factory without walls', as well as key concepts such as multitude and immaterial labour. The impact of these ideas and of Operaismo politics more generally on the precarity movement is then considered in the second section, discussing some of the issues that have animated debate both within and outside this movement, which has often treated cultural workers as exemplifying the experiences of a new 'precariat'. In the third and final section of the paper we turn to the empirical literature about cultural work, pointing to its main features before bringing it into debate with the ideas already discussed. Several points of overlap and critique are elaborated -- focusing in particular on issues of affect, temporality, subjectivity and solidarity

The coherence of inconsistencies: Attitude–behaviour gaps and new consumption communities

Despite the growing success of well-marketed environmentally-friendly products, there remains a gap between consumers’ positive attitudes toward green issues and products, and their inconsistent and often conflicting consumption behaviour. Indeed, this is a challenge for social marketers seeking to advance the sustainability agenda. Therefore, this study problematises what has been conceptualised as attitude-behaviour gaps (Boulstridge and Carrigan 2000), and explores how groups of consumers have re-construed such practices and their meanings through the formation of New Consumption Communities (Szmigin, Carrigan and Bekin 2007). Multi-sited ethnographic findings illustrate the social processes through which ethical and green forms of consumption are established and normalised. Findings also stress the importance of normative and habitual reframing through ‘ethical spaces’ (Barnett et al. 2005) in establishing and maintaining increased consistency in participants’ consumption meanings, behaviours and goals. Thus, we re-frame attitude-behaviour gaps as coherent inconsistencies, which allows for a move away from solely trying to explain and change individual consumer behaviour, to identifying how suitable upstream and downstream (Verplanken and Wood 2006) approaches and policies can be used to facilitate more sustainable forms of consumption

Challenges and constraints in developing and implementing sports policy and provision in Antigua and Barbuda: which way now for a small island state?

This paper examines the challenges and constraints of sport policy agenda setting and policy development in a small nation context of Antigua and Barbuda. It also aims to understand and explore existing limitations, issues and trajectories in sport policy implementation. The project draws upon a mixed-methods approach encompassing documentary analysis, 30 in-depth interviews and visual methodology in the form of photo observations. Through this methodology, the purpose of the paper is to open up sport policy agendas allowing the ‘voices’ of those local populations, policymakers, coaches and volunteers to be heard within the context of this study and wider sport policy research. Initial findings indicate sport and physical activity as a contested policy priority, barriers in cross-departmental collaboration, elite sport and performance agenda dilemmas and considerable limitations in third sector human infrastructure and physical facilities. Implications from this small nation sport policy context highlight the need for improved public policy problem definition and the need for clarity in agenda setting within tiers of the evolving sport policy community. Finally, the tentative potential positive policy spaces for future implementation and lessons in policy design involving national, regional and local actors and agencies are identified

Rare Pathogenic Variants in IL36RN Underlie a Spectrum of Psoriasis-Associated Pustular Phenotypes

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