Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target

Background: The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs upregulated in the airway wall, effectively suppressed Th2-driven airway inflammation and other features of asthma. In the present study, we extended investigation of the therapeutic potential of miRNA inhibition to our well-established model of chronic asthma. Methods: Female BALB/c mice were systemically sensitised with ovalbumin (OVA) and chronically challenged with low mass concentrations of aerosolised OVA for up to 6 weeks. Airway tissue was obtained by blunt dissection and RNA was isolated for miRNA profiling. On the basis of the results obtained, animals were subsequently treated with either an antagomir to miR-126 (ant-miR-126) or a scrambled control antagomir once weekly during the 6 weeks of chronic challenge, and the effects on airway inflammation and remodelling were assessed using established morphometric techniques. Results: Compared to naïve mice, there was selective upregulation of a modest number of miRNAs, notably miR-126, in the airway wall tissue of chronically challenged animals. The relative increase was maximal after 2 weeks of inhalational challenge and subsequently declined to baseline levels. Compared to treatment with the scrambled control, ant-miR-126 significantly reduced recruitment of intraepithelial eosinophils, but had no effect on the chronic inflammatory response, or on changes of airway remodelling. Conclusions: In this model of chronic asthma, there was an initial increase in expression of a small number of miRNAs in the airway wall, notably miR-126. However, this later declined to baseline levels, suggesting that sustained changes in miRNA may not be essential for perpetuation of chronic asthma. Moreover, inhibition of miR-126 by administration of an antagomir suppressed eosinophil recruitment into the airways but had no effect on chronic inflammation in the airway wall, or on changes of remodelling, suggesting that multiple miRNAs are likely to regulate the development of these lesions

An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions

Hopeful, Harmless, and Heroic

There has been a notable increase in the public visibility of girl activists in the past ten years. In this article, I analyze media narratives about several individual girl activists to highlight key components of the newly desirable figure of the girl activist. After tracing the expansion of girl power discourses from an emphasis on individual empowerment to the invocation of girls as global saviors, I argue that girls are particularly desirable figures for public consumption because the encoding of girls as symbols of hope helps to resolve public anxieties about the future, while their more radical political views are managed through girlhood’s association with harmlessness. Ultimately, the figure of the hopeful and harmless girl activist hero is simultaneously inspirational and demobilizing

Continually RedefiningProtagonismo: The Peruvian Movement of Working Children and Political Change, 1976–2015

Activists in the Peruvian working children’s movement have been theorizing about “children’s protagonismo” for nearly 40 years. Changing political contexts and the infusion of discourses from other social movements have produced three major sets of meanings for this concept, each reflecting different dynamics in Peruvian social movement history. First, the concept, infused with ideas from liberation theology and Latin American engagements with Marxism, was primarily understood in terms of class struggle and collective organization. Second, because of opportunities and threats in the 1980s and 1990s, it became more closely associated with children’s rights frameworks. Third, since the early 2000s, the movement’s approach to protagonismo has drawn on indigenous theories of interdependence and relationality to challenge the individualism of neoliberal capitalism and governmentality. In holding these diverse ideological commitments together, the concept has allowed the movement of working children to communicate across multiple discursive communities.Los activistas del movimiento de los niños trabajadores peruanos han teorizado sobre el “protagonismo infantil” durante casi 40 años. Los cambios en el contexto político y la influencia de discursos pertenecientes a otros movimientos sociales han generado tres grandes conjuntos de significado alrededor de este concepto, cada uno de los cuales reflejando distintas dinámicas en la historia del movimiento social peruano. Primero, el concepto se entendió en términos de clase imbuidos por ideas de la teología de la liberación, así como actitudes latinoamericanas de compromiso con el marxismo y la organización colectiva. Posteriormente, a raíz de las oportunidades y amenazas de las décadas de 1980 y 90, se relacionó de manera más estrecha con el marco de los derechos del niño. Desde principios de la década del 2000, el enfoque del protagonismo se ha ligado a teorías indígenas de la interdependencia y la relacionalidad para desafiar el individualismo del capitalismo neoliberal y la gobernabilidad. Al unir tal diversidad de compromisos ideológicos, el concepto ha permitido que el movimiento de los niños trabajadores tenga voz en múltiples comunidades discursivas

“Adults talk too much”: Intergenerational dialogue and power in the Peruvian movement of working children

Recent work on children’s participatory rights has suggested the need to pay attention to adult–child relationships and foster intergenerational dialogue. Drawing on ethnographic observation and in-depth interviews with the Peruvian movement of working children, this article explores the ambiguous and complex status of adult voice in organizations that have taken up children’s participation. The ideal of egalitarian intergenerational collaboration is incredibly difficult to implement given the broader social context of age-based inequality. Despite good intentions and a deep commitment to children’s agency and authority, adults and children in this movement continue to replicate deeply structured patterns of behavior that give adults greater power