Cell lineage-specific mitochondrial resilience during mammalian organogenesis

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

Critical research on populism: Nine rules of engagement

This article formulates precise questions and ‘rules of engagement’ designed to advance our understanding of the role populism can and should play in the present political conjuncture, with potentially significant implications for critical management and organization studies and beyond. Drawing on the work of Ernesto Laclau and others working within the post-Marxist discourse theory tradition, we defend a concept of populism understood as a form of reason that centres around a claim to represent ‘the people’, discursively constructed as an underdog in opposition to an illegitimate ‘elite’. A formal discursive approach to populism brings with it important advantages. For example, it establishes that a populist logic can be invoked to further very different political goals, from radical left to right, or from progressive to regressive. It sharpens too our grasp of important issues that are otherwise conflated and obfuscated. For instance, it helps us separate out the nativist and populist dimensions in the discourses of the United Kingdom Independence Party (UKIP), Trump or the Front National (FN). Our approach to populism, however, also points to the need to engage with the rhetoric about populism, a largely ignored area of critical research. In approaching populism as signifier, not only as a concept, we stress the added need to focus on the uses of the term ‘populism’ itself: how it is invoked, by whom, and to what purpose and effect. This, we argue, requires that we pay more systematic attention to anti-populism and ‘populist hype’, and reflect upon academia’s own relation to populism and anti-populism

Fantasies of subjugation: a discourse theoretical account of British policy on the European Union

The decision by the UK government to hold a referendum on Britain’s membership of the European Union (EU) marks an important development in policy towards the EU. Policy changes of this kind must be understood in the historical and political context in which they occur. This includes the framing of the policy issues within public discourse. In the UK, policies are formed in a discursive environment which is overwhelmingly hostile towards the EU. Debates are structured by a predominantly Euroskeptic discourse which emphasizes the UK’s separation and heterogeneity from the rest of the EU. Drawing on the logics of critical explanation, this article examines the structure and affective power of Euroskeptic discourses which dictate the terms of the EU debate. It presents a case study of the recent EU treaty revision process, culminating in the Treaty of Lisbon. In so doing, it enables a deeper understanding of recent policy developments

The Wetting Behavior of Polymer Droplets: Effects of Droplet Size and Chain Length

Monte Carlo computer simulations were utilized to probe the behavior of homopolymer droplets adsorbed at solid surfaces as a function of the number of chains making up the droplets and varying droplet sizes. The wetting behavior is quantified via the ratio of the perpendicular to the parallel component of the effective radii of gyration of the droplets and is analyzed further in terms of the adsorption behavior of the polymer chains and the monomers that constitute the droplets. This analysis is complemented by an account of the shape of the droplets in terms of the principal moments of the radius of gyration tensor. Single-chain droplets are found to lie flatter and wet the substrate more than chemically identical multichain droplets, which attain a more globular shape and wet the substrate less. The simulation findings are in good agreement with atomic force microscopy experiments. The present investigation illustrates a marked dependence of wetting and adsorption on certain structural arrangements and proposes this dependence as a technique through which polymer wetting may be tuned

Cell lineage-specific mitochondrial resilience during mammalian organogenesis

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

Cohesion as ‘common sense’: Everyday narratives of community and cohesion in New Labour’s Britain

The final, definitive version of this paper has been published in Politics, Vol. 36(3) July 2016, DOI: 10.1177/0263395715620811 published by SAGE Publishing. All rights reservedThis article engages with popular narratives of community and cohesion, explored through a series of focus groups in Bradford and Birmingham. This article argues that the participants interviewed used discourses propagated by government to make sense of these narratives in their neighbourhoods and communities. The use of these discourses constructs what Gramsci calls a ‘common sense’ position, which legitimises a specific and targeted notion of cohesion. However, participants can contaminate these discourses, which can lead to subtle changes or explicit challenges to dominant discourses on community and cohesion in the United Kingdom.Peer reviewe

The cultural grammar of governance: The UK Code of Corporate Governance, reflexivity, and the limits of 'soft' regulation

We identify limits of ‘reflexive governance’ by examining the UK Code of Corporate Governance that is celebrated for its ‘reflexivity’. By placing the historical genesis of the Code within its politico-economic context, it is shown how its scope and penetration is impeded by a shallow, ‘single loop’ of reflexivity. Legitimized by agency theory, the Code is infused by a ‘cultural grammar’ that perpetuates relations of shareholder primacy as it restricts accountability to narrow forms of information disclosure directed exclusively at shareholders. Engagement of a deeper, ‘double loop’ reflexivity allows account to be taken of the historical conditions and theoretical conceptions that shape practices and outcomes of corporate governance. Only then is it possible to disclose, challenge and reform narrow conceptions, boundaries and workings of ‘reflexive governance’