Candidate Genes Detected in Transcriptome Studies Are Strongly Dependent on Genetic Background

Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds

'You were quiet - I did all the marching': Research processes involved in hearing the voices of South Asian girls

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 A B Academic Publishers.This article provides insights into the outcomes of reflection following two interview approaches used to explore narratives of the lived, individual experiences of South-Asian girls living in West London. In attempting to illuminate and re-present the cultural experiences as told by these girls, the choice of interview approach became critical in allowing the voices to be effectively heard (Rogers, 2005). This article therefore considers how a semi-structured interview approach offered valuable insights into the girls' experiences but became constraining for both researcher and participant in unveiling the complexity and depth of their lives. These constraints emerged through reflection by both participants and researcher. As a result of reflexivity during the research process, the researcher moved towards the use of research conversations during the second phase of the study. Ultimately the study revealed how the girls felt empowered by the opportunity to narrate their individual experiences and tell of their lives. In narrating their reflections on being part of the research, there was a clear recognition that the process facilitated the articulation of new voices and ‘multi-voicedness’ (Moen, 2006

Critical Race Theory and Education: racism and anti-racism in educational theory and praxis

What is Critical Race Theory (CRT) and what does it offer educational researchers and practitioners outside the US? This paper addresses these questions by examining the recent history of antiracist research and policy in the UK. In particular, the paper argues that conventional forms of antiracism have proven unable to keep pace with the development of increasingly racist and exclusionary education polices that operate beneath a veneer of professed tolerance and diversity. In particular, contemporary antiracism lacks clear statements of principle and theory that risk reinventing the wheel with each new study; it is increasingly reduced to a meaningless slogan; and it risks appropriation within a reformist “can do” perspective dominated by the de-politicized and managerialist language of school effectiveness and improvement. In contrast, CRT offers a genuinely radical and coherent set of approaches that could revitalize critical research in education across a range of inquiries, not only in self-consciously "multicultural" studies. The paper reviews the developing terrain of CRT in education, identifying its key defining elements and the conceptual tools that characterise the work. CRT in education is a fast changing and incomplete project but it can no longer be ignored by the academy beyond North America

All the way from … authenticity and distance in world music production

World music and the narratives it produces are at the very centre of a formerly transnational production and consumption process. However, the shortened distance between the sites of production and consumption of this good, brought on by migration and greater participation, has created a dilemma for the UK-based artists who perform it: how to maintain authenticity without the added value of ‘distance’. Therefore, the aim of this article is to examine the ways in which musicians and other participants attempt to overcome this problem and in doing so (re)-construct particular aspects of their identity. Rather than being just another critique on authenticity, this article uses distance as an organizing concept in understanding the challenges facing world music production in the UK

Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

INTRODUCTION: Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin. METHODS: Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75. RESULTS: We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines. CONCLUSION: Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action

Metabolomics of aging assessed in individual parasitoid wasps

Metabolomics studies of low-biomass organisms, such as small insects, have previously relied on the pooling of biological samples to overcome detection limits, particularly using NMR. We show that the differentiation of metabolite profiles of individual 1 mg parasitoid wasps of different ages is possible when using a modified sample preparation and a combination of untargeted NMR and LC-MS based metabolomics. Changes were observed between newly emerged and older wasps in glycerolipids, amino acids and circulatory sugars. This advance in chemical profiling has important implications for the study of the behaviour and ecology of parasitoids and many other species of small organisms because predictions and observations are typically made at the level of the individual. Thus, the metabolomic state of low-biomass individuals can now be related to their behaviour and ecological performance. We discuss specifically the utility of age-related metabolomic profiling but our new approach can be applied to a wide range of biological research

Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells

Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers