Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

An Uncertain Dominion: Irish Psychiatry, Methadone, and the Treatment of Opiate Abuse

This paper investigates some productive ambiguities around the medical administration of methadone in the Republic of Ireland. The tensions surrounding methadone maintenance therapy (MMT) are outlined, as well as the sociohistorical context in which a serious heroin addiction problem in Ireland developed. Irish psychiatry intervened in this situation, during a time of institutional change, debates concerning the nature of addiction, moral panics concerning heroin addiction in Irish society and the recent boom in the Irish economy, known popularly as the Celtic Tiger. A particular history of this sort illuminates how technologies like MMT become cosmopolitan, settling into, while changing, local contexts

The Impact of Neighbourhood Planning and Localism on House-building in England

© 2016 IBF, The Institute for Housing and Urban ResearchThe devolution of governance to communities is an integral aspect of the state strategy of localism but may conflict with a spatial restructuring dedicated to the liberalization of economic growth. In England, community opposition to house-building has been cited as one of the key factors in the decline in new housing supply over the last decade. The policy of neighbourhood planning was introduced there in 2011 to overcome this opposition by devolving limited powers to communities to influence development. It was anticipated that giving communities the right to draw up neighbourhood development plans would secure their compliance with a pro-growth agenda and increase the number of sites allocated for housing. This paper explores the impact of neighbourhood planning in England on housing development and analyses its lessons for the state strategy of localism. It argues that neighbourhood planning is emerging as the proponent of sustainability and social purpose in the English housing market, in conflict with the corporate interests of a liberalized housing development market

Nature’s nations: the shared conservation history of Canada and the USA

Historians often study the history of conservation within the confines of national borders, concentrating on the bureaucratic and political manifestations of policy within individual governments. Even studies of the popular expression of conservationist ideas are generally limited to the national or sub-national (province, state, etc.) scale. This paper suggests that conservationist discourse, policy and practice in Canada and the USA were the products of a significant cross-border movement of ideas and initiatives derived from common European sources. In addition, the historical development of common approaches to conservation in North America suggests, contrary to common assumptions, that Canada did not always lag behind the USA in terms of policy innovation. The basic tenets of conservation (i.e. state control over resource, class-based disdain for subsistence hunters and utilitarian approaches to resource management) have instead developed at similar time periods and along parallel ideological paths in Canada and the USA

William S. Burroughs

Presenta una serie de fotocopias-collage del auto

Reading: William S. Burroughs

In this audiovisual recording from March 22, 1978 as part of the 9th annual UND Writing Conference: “The Mirror and the Lamp,” William S. Burroughs reads an early version of “M.O.B.--My Own Business,” “Bugger the Queen,” “Roosevelt After Inauguration: A New Introduction,” “Roosevelt After Inauguration,” “Why I Stopped Wanting to Be President,” an excerpt from Cities of the Red Night, and “The Do-Rights.