263 research outputs found

    Indoctrination, empowerment or emancipation? The role of ELT in global society

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    In a wide-ranging talk at the IATEFL BESIG-GISIG conference in Berlin in October 2019, Steve Brown addressed the current state of English language teaching and what he sees as its increasing commodification. In his view, we are promoting an ideology that monetises learning which requires English and English language programmes to be itemised as marketable commodities. He also states that we are stifling any capacities that might exist within ELT to critically explore and challenge current power structures and processes within global society. Drawing on the work of critical pedagogues such as Paolo Freire and Henry Giroux, he<br/>invited the audience to explore alternatives that promote the emancipation of learners, as opposed to their indoctrination. We should allow learners to identify examples of social injustice and take steps to redress imbalances. This would eventually lead to a model of ELT that is socially responsible but also more congruent with widely accepted principles of language acquisition. This article presents a discussion between Steve Brown and Roy Bicknell, and explores some of the many points which were raised through his talk

    Pulmonary MicroRNA changes alter angiogenesis in chronic obstructive pulmonary disease and lung cancer

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    The pulmonary endothelium is dysfunctional in chronic obstructive pulmonary disease (COPD), a known risk factor for lung cancer. The pulmonary endothelium is altered in emphysema, which is disproportionately affected by cancers. Gene and microRNA expression differs between COPD and non-COPD lung. We hypothesised that the alteration in microRNA expression in the pulmonary endothelium contributes to its dysfunction. A total of 28 patients undergoing pulmonary resection were recruited and endothelial cells were isolated from healthy lung and tumour. MicroRNA expression was compared between COPD and non-COPD patients. Positive findings were confirmed by quantitative polymerase chain reaction (qPCR). Assays assessing angiogenesis and cellular migration were conducted in Human Umbilical Vein Endothelial Cells (n = 3–4) transfected with microRNA mimics and compared to cells transfected with negative control RNA. Expression of miR-181b-3p, miR-429 and miR-23c (all p < 0.05) was increased in COPD. Over-expression of miR-181b-3p was associated with reduced endothelial sprouting (p < 0.05). miR-429 was overexpressed in lung cancer as well and exhibited a reduction in tubular formation. MicroRNA-driven changes in the pulmonary endothelium thus represent a novel mechanism driving emphysema. These processes warrant further study to determine if they may be therapeutic targets in COPD and lung cancer

    A new procedure for determining the genetic basis of a physiological process in a non-model species, illustrated by cold induced angiogenesis in the carp

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    <p>Abstract</p> <p>Background</p> <p>Physiological processes occur in many species for which there is yet no sequenced genome and for which we would like to identify the genetic basis. For example, some species increase their vascular network to minimise the effects of reduced oxygen diffusion and increased blood viscosity associated with low temperatures. Since many angiogenic and endothelial genes have been discovered in man, functional homolog relationships between carp, zebrafish and human were used to predict the genetic basis of cold-induced angiogenesis in <it>Cyprinus Carpio </it>(carp). In this work, carp sequences were collected and built into contigs. Human-carp functional homolog relationships were derived via zebrafish using a new Conditional Stepped Reciprocal Best Hit (CSRBH) protocol. Data sources including publications, Gene Ontology and cDNA libraries were then used to predict the identity of known or potential angiogenic genes. Finally, re-analyses of cold carp microarray data identified carp genes up-regulated in response to low temperatures in heart and muscle.</p> <p>Results</p> <p>The CSRBH approach outperformed all other methods and attained 8,726 carp to human functional homolog relationships for 16,650 contiguous sequences. This represented 3,762 non-redundant genes and 908 of them were predicted to have a role in angiogenesis. The total number of up-regulated differentially expressed genes was 698 and 171 of them were putatively angiogenic. Of these, 5 genes representing the functional homologs NCL, RHOA, MMP9, GRN and MAPK1 are angiogenesis-related genes expressed in response to low temperature.</p> <p>Conclusion</p> <p>We show that CSRBH functional homologs relationships and re-analyses of gene expression data can be combined in a non-model species to predict genes of biological interest before a genome sequence is fully available. Programs to run these analyses locally are available from <url>http://www.cbrg.ox.ac.uk/~jherbert/</url>.</p

    RhoJ/TCL Regulates Endothelial Motility and Tube Formation and Modulates Actomyosin Contractility and Focal Adhesion Numbers

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    Objective—RhoJ/TCL was identified by our group as an endothelial-expressed Rho GTPase. The aim of this study was to determine its tissue distribution, subcellular localization, and function in endothelial migration and tube formation. Methods and Results—Using in situ hybridization, RhoJ was localized to endothelial cells in a set of normal and cancerous tissues and in the vasculature of mouse embryos; endogenous RhoJ was localized to focal adhesions by immunofluorescence. The proangiogenic factor vascular endothelial growth factor activated RhoJ in endothelial cells. Using either small interfering (si)RNA-mediated knockdown of RhoJ expression or overexpression of constitutively active RhoJ (daRhoJ), RhoJ was found to positively regulate endothelial motility and tubule formation. Downregulating RhoJ expression increased focal adhesions and stress fibers in migrating cells, whereas daRhoJ overexpression resulted in the converse. RhoJ downregulation resulted in increased contraction of a collagen gel and increased phospho–myosin light chain, indicative of increased actomyosin contractility. Pharmacological inhibition of Rho-kinase (which phosphorylates myosin light chain) or nonmuscle myosin II reversed the defective tube formation and migration of RhoJ knockdown cells. Conclusion—RhoJ is endothelial-expressed in vivo, activated by vascular endothelial growth factor, localizes to focal adhesions, regulates endothelial cell migration and tube formation, and modulates actomyosin contractility and focal adhesion numbers

    Sunitinib treatment enhances metastasis of innately drug resistant breast tumors

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    Anti-angiogenic therapies have failed to confer survival benefits in patients with metastatic breast cancer (mBC). However, to date there has not been an inquiry into roles for acquired versus innate drug resistance in this setting. In this study, we report roles for these distinct phenotypes in determining therapeutic response in a murine model of mBC resistance to the anti-angiogenic tyrosine kinase inhibitor sunitinib. Using tumor measurement and vascular patterning approaches, we differentiated tumors displaying innate versus acquired resistance. Bioluminescent imaging of tumor metastases to the liver, lungs and spleen revealed that sunitinib administration enhances metastasis, but only in tumors displaying innate resistance to therapy. Transcriptomic analysis of tumors displaying acquired versus innate resistance allowed the identification of specific biomarkers, many of which have a role in angiogenesis. In particular, aquaporin-1 upregulation occurred in acquired resistance, mTOR in innate resistance, and pleiotrophin in both settings, suggesting their utility as candidate diagnostics to predict drug response or to design tactics to circumvent resistance. Our results unravel specific features of antiangiogenic resistance, with potential therapeutic implications

    A computational framework for gene regulatory network inference that combines multiple methods and datasets

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    <p>Abstract</p> <p>Background</p> <p>Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective.</p> <p>Results</p> <p>This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies.</p> <p>Conclusions</p> <p>The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.</p

    Gene signatures in wound tissue as evidenced by molecular profiling in the chick embryo model

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    <p>Abstract</p> <p>Background</p> <p>Modern functional genomic approaches may help to better understand the molecular events involved in tissue morphogenesis and to identify molecular signatures and pathways. We have recently applied transcriptomic profiling to evidence molecular signatures in the development of the normal chicken chorioallantoic membrane (CAM) and in tumor engrafted on the CAM. We have now extended our studies by performing a transcriptome analysis in the "wound model" of the chicken CAM, which is another relevant model of tissue morphogenesis.</p> <p>Results</p> <p>To induce granulation tissue (GT) formation, we performed wounding of the chicken CAM and compared gene expression to normal CAM at the same stage of development. Matched control samples from the same individual were used. We observed a total of 282 genes up-regulated and 44 genes down-regulated assuming a false-discovery rate at 5% and a fold change > 2. Furthermore, bioinformatics analysis lead to the identification of several categories that are associated to organismal injury, tissue morphology, cellular movement, inflammatory disease, development and immune system. Endothelial cell data filtering leads to the identification of several new genes with an endothelial cell signature.</p> <p>Conclusions</p> <p>The chick chorioallantoic wound model allows the identification of gene signatures and pathways involved in GT formation and neoangiogenesis. This may constitute a fertile ground for further studies.</p

    Nonlinear stability of relativistic sheared planar jets

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    The linear and non-linear stability of sheared, relativistic planar jets is studied by means of linear stability analysis and numerical hydrodynamical simulations. Our results extend the previous Kelvin-Hemlholtz stability studies for relativistic, planar jets in the vortex sheet approximation performed by Perucho et al. (2004a,b) by including a shear layer between the jet and the external medium and more general perturbations. The models considered span a wide range of Lorentz factors (2.5202.5-20) and internal energies (0.08c260c20.08 c^2-60 c^2) and are classified into three classes according to the main characteristics of their long-term, non-linear evolution. We observe a clear separation of these three groups in a relativistic Mach-number Lorentz-factor plane. Jets with a low Lorentz factor and small relativistic Mach number are disrupted after saturation. Those with a large Lorentz factor and large relativistic Mach number are the stablest, due to the appearance of short wavelength resonant modes which generate local mixing and heating in the shear layer around a fast, unmixed core, giving a plausible solution for the problem of the long-term stability of relativistic jets. A third group is present between them, including jets with intermediate values of Lorentz factor and relativistic Mach number, which are disrupted by a slow process of mixing favored by an efficient and continuous conversion of kinetic into internal energy. In the long term, all the models develop a distinct transversal structure (shear/transition layers) as a consequence of KH perturbation growth, depending on the class they belong to. The properties of these shear layers are analyzed in connection with the parameters of the original jet models.Comment: accepted for publication in A&A (in press). High resolution plots, figures and Appendices of the paper will be found in the online version of the paper in A&A, and on request to [email protected]
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