Epigenetic modification of cytosines fine tunes the stability of i-motif DNA

i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications

Austerity: Neoliberal dreams come true?

The 2008 global economic crisis paved the way for the construction of a new, elitedriven, capitalcentric, shrunken welfare state project founded on ideology disguised as pragmatism and objective ‘truths’. Today, welfare states exist in a context in which a new politics of austerity sets the parameters of the debate. Austerity incorporates the neoliberal desire to shrink the (social welfare) state, deregulate labour markets and emphasise private markets as the drivers of growth, enabling a reconfiguration of the interests of capital, the needs of people and the role of the state. The new politics of austerity looks like a ‘dream come true’ for neoliberals. Or is it? There is also a powerful counternarrative that suggests that the global crisis exposed the fundamental weaknesses and limitations of neoliberalism and forced policy makers to question core principles and change direction. Focusing on the International Monetary Fund (IMF), perhaps the preeminent global neoliberal interlocutor, and using quantitative textual analysis, the article locates some evidence of movement, but little to suggest that the fundamental assumptions of neoliberalism have been displaced

Integrity of practice in lecturers' accounts of teaching decisions

This article draws on data collected during a funded research project on undergraduate teaching within a single discipline, social policy. Starting from observations drawn from analysis of the interview transcripts, the article develops the concept of 'integrity of practice' from the literature on reflective practice and the scholarship of teaching. Integrity of practice enables the lecturer to explain and justify decisions about teaching and learning activities to his or herself, as well as to students, colleagues and institutional and other policy makers. It provides for core stability in times of great changes in higher education and enables innovative practice to be justified and disseminated. © 2005 Society for Research into Higher Education