Why Did Cornwall Vote for Brexit? Assessing the Implications for EU Structural Funding Programmes

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.In the 2016 referendum on UK EU membership, regions which benefitted from high levels of structural funds voted to leave the EU. This was unexpected given the Europeanisation processes expected of the funds in terms of identity and loyalty. Within this case study of Cornwall, we use qualitative methods to assess why this happened and the implications for future structural funding programmes. We find that the rationale behind the Brexit vote was less about the EU as an institution, but was a reflection of the deep levels of uncertainty, insecurity, and frustration that people felt about governance decisions, scarce resources, and the future for themselves and their children. This created a situation where people looked to the nation state for support and security, and were fearful of post-national forms of identification and governance. Consequently, EU support is imagined as being organised by ‘elites’, for elites, rather than benefitting local communities. We suggest breaking down some of the barriers that have arisen through a participatory approach to development decision-making, greater flexibility to regional priorities, and forms of funding that individuals might apply to – such as a skills pot to facilitate easier access to further education and training.Economic and Social Research Council (ESRC

Environmental regulation of male fertility is mediated through Arabidopsis transcription factors bHLH89, 91, and 10

Formation of functional pollen and successful fertilization rely on the spatial and temporal regulation of anther and pollen development. This process responds to environmental cues to maintain optimal fertility despite climatic changes. Arabidopsis transcription factors basic helix–loop–helix (bHLH) 10, 89, and 91 were previously thought to be functionally redundant in their control of male reproductive development, however here we show that they play distinct roles in the integration of light signals to maintain pollen development under different environmental conditions. Combinations of the double and triple bHLH10,89,91 mutants were analysed under normal (200 μmol m–2 s–1) and low (50 μmol m–2 s–1) light conditions to determine the impact on fertility. Transcriptomic analysis of a new conditionally sterile bhlh89,91 double mutant shows differential regulation of genes related to sexual reproduction, hormone signal transduction, and lipid storage and metabolism under low light. Here we have shown that bHLH89 and bHLH91 play a role in regulating fertility in response to light, suggesting that they function in mitigating environmental variation to ensure fertility is maintained under environmental stress

War Craft: The embodied politics of making war

This article makes the case for examining war from what Stephanie Bunn calls a ‘making point of view’. Makers and their material production of and for war have been neglected in our accounts of war, security and international relations. An attention to processes of making for war can reveal important things about how such processes are lived and undertaken at the level of the body. The article focuses on the particular phenomena of martial craft labour – the recreational making of ‘stuff’, including hats and pillowcases, by civilians for soldiers. To explore embodiment within this social site, an ethnographic method is outlined that enables the reading of objects as embodied texts, the observation of others in processes of making, and the undertaking of making by the researcher. Analysing embodied registers of aesthetic expression and the social values that attend such crafting for war reveals how this making is a space through which intimate embodied, emotional circulations undertake work for liberal-state and military-institutional logics and objectives, obscure violence, normalize war, and produce the military as an abstract social cause. Beyond the immediate empirical focus of this article, a much wider political entanglement of violence, embodiment and material production necessitates a concerted research agenda

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia

In common with other E2F1 responsive genes such as p14ARF and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium

RNASeq analysis of differentiated keratinocytes reveals a massive response to late events during human papillomavirus type 16 infection, including loss of epithelial barrier function.

The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log2 = 1.8, 3.5-fold change) 670 genes were downregulated and 296 genes were up-regulated. HPV down-regulated many genes involved in epithelial barrier function that involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant, CCL20, and proinflammatory cytokines, IL1A and IL1B. However, IRF1, IFNκ and viral restriction factors (IFIT1, 2, 3, 5, OASL, CD74, RTP4) were up-regulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions and cell adhesion. qPCR and western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress.IMPORTANCE Human papillomavirus (HPV) genome amplification and capsid formation takes place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNASeq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3000 genes were differentially expressed in keratinocyte due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into virus-host interaction crucial for production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle

Home self-testing kits: helpful or harmful?

Over recent years access to self-testing kits (part of the direct-to-consumer testing market) has been expanding.1 These tests may be purchased online or in pharmacies and are performed without input from health professionals. Samples taken are either processed at home or sent to a laboratory, and may offer screening, diagnosis, monitoring, or information about the risk of a disease. These tests are likely to generate additional primary care consultations as they become more widely available. Here we consider the processes by which self-tests conducted at home are regulated, their accuracy and the benefits and risks of this new diagnostic process