Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados Unido

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Impossible protest: noborders in Calais

Since the closure of the Red Cross refugee reception centre in Sangatte, undocumented migrants in Calais hoping to cross the border to Britain have been forced to take refuge in a number of squatted migrant camps, locally known by all as ‘the jungles.’ Unauthorised shanty-like residences built by the migrants themselves, living conditions in the camps are very poor. In June 2009, European ‘noborder’ activists set up a week-long protest camp in the area with the intention of confronting the authorities over their treatment of undocumented migrants. In this article, we analyse the June 2009 noborder camp as an instance of ‘immigrant protest.’ Drawing on ethnographic materials and Jacques Rancière's work on politics and aesthetics, we construct a typology of forms of border control through which to analyse the different ways in which the politics of the noborder camp were staged, performed and policed. Developing a critique of policing practices which threatened to make immigrant protest ‘impossible’, we highlight moments of protest which, through the affirmation of an ‘axiomatic’ equality, disrupted and disarticulated the borders between citizens and non-citizens, the political and non-political

Digitalizing the welfare state: citizenship discourses in Danish digitalization strategies from 2002 to 2015

As governments worldwide become increasingly reliant on digital technologies and e-government, ‘digital citizenship’ has become an important topic for research and policy-makers alike. While often described as the contemporary ‘ideal’ of citizenship, research has tended to downplay the normative dimensions of digital citizenship. Counter to such depoliticized approaches, this article argues that the digital citizen is a deeply political figure. Through a discourse-theoretical analysis of Danish governmental digitalization strategies from 2002 to 2015, the article shows how these have relied on a very particular image of the digital citizen. More specifically, we showcase how this figure has reproduced neoliberal conceptions of subjectivity, concerned with efficiency, productivity, individualization and collective responsibilization. By shedding light on these novel links between neoliberal and digital citizenship, the article challenges current views on digitalization. The article foregrounds how digitalization serves to reproduce and recast already-existing political rationalities and must be considered in relation to neoliberal hegemony.As governments worldwide become increasingly reliant on digital technologies and e-government, ‘digital citizenship’ has become an important topic for research and policy-makers alike. While often described as the contemporary ‘ideal’ of citizenship, research has tended to downplay the normative dimensions of digital citizenship. Counter to such depoliticized approaches, this article argues that the digital citizen is a deeply political figure. Through a discourse-theoretical analysis of Danish governmental digitalization strategies from 2002 to 2015, the article shows how these have relied on a very particular image of the digital citizen. More specifically, we showcase how this figure has reproduced neoliberal conceptions of subjectivity, concerned with efficiency, productivity, individualization and collective responsibilization. By shedding light on these novel links between neoliberal and digital citizenship, the article challenges current views on digitalization. The article foregrounds how digitalization serves to reproduce and recast already-existing political rationalities and must be considered in relation to neoliberal hegemony

Tracking the reflexivity of the (dis)engaged citizen: some methodological reflections

The relationship between governments and citizens in many contemporary democracies is haunted by uncertainty and sociologists face the task of listening effectively to citizens’ own reflections on this uncertain relationship. This article reflects on the qualitative methodology of a recently completed UK project which used a combination of diary and multiple interviews/ focus groups to track over a fieldwork period of up to a year citizens’ reflections on their relationship to a public world and the contribution to this of their media consumption. In particular, the article considers how the project’s multiple methods enabled multiple angles on the inevitable artificiality and performative dimension of the diary process, resulting in rich data on people’s complex reflections on the uncertain position of the contemporary citizen

Citizenship and Inclusion: Rethinking the Analytical Category of Noncitizenship

The paper problematises the category of noncitizenship. It traces its trajectory in accounts of inclusive citizenship and argues that it is difficult to theorise it as a distinct theoretical category outside of citizenship. To support this argument, the paper distinguishes between a pluralist, political and democratic variant of accounts of inclusive citizenship and it shows how they all end up reducing noncitizenship to a journey to citizenship. To overcome this limit, the paper develops the idea of subversive politicisation and suggests that injustices and inequalities can be challenged without falling back on the vocabulary of citizenship

Peuples mobiles : configurations transversales

Cet essai tente de penser les « peuples mobiles » comme concept politique. Je considère les peuples mobiles comme norme et non exception, davantage comme des sujets politiques que des peuples sujets. Après avoir discuté la tension entre « peuples » et « mobiles », je m’appuierai sur l’ontologie historique de Ian Hacking pour comprendre comment un peuple advient. Et pour comprendre l’advenir du peuple, ou plutôt la tension entre un peuple qui se constitue comme un tout et ces peuples qui restent à la marge, je m’appuie sur Giorgio Agamben, Jacques Rancière et Ernesto Laclau, qui ont identifié cette tension comme problème fondamental de la pensée politique « occidentale ». Toutefois, leur indifférence au territoire me rapproche des travaux de James Scott sur les premiers États, qui remettent en question notre appréhension usuelle des peuples comme initialement sédentaires. Sa description du mécanisme selon lequel les « barbares » (peuples mobiles) finissent par être considérés comme une menace envers les peuples sédentaires nous permet de comprendre cette tension. Dès lors s’ouvre la voie à une réflexion sur les peuples mobiles en tant que concept politique.This essay is an attempt to think “mobile peoples” as a political concept. I consider mobile peoples as a norm rather than an exception and as political subjects rather than subject peoples. After discussing the tension between “mobile” and ”peoples”, I draw on Ian Hacking’s historical ontology for understanding how a people comes to be. For understanding how the people comes to be, or rather, how the tension between a people that constitutes itself as a whole and those peoples that remain as residual parts, I draw on Giorgio Agamben, Jacques Rancière, and Ernesto Laclau as authors who identified this tension as a fundamental problem of “Western” political thought. Yet, their inattention to territory draws me to James Scott whose work on early states challenges how we have come to understand the people as sedentary in the first place. His account of how “barbarians” (mobile peoples) came to be seen as a threat to sedentary peoples enables us to understand that tension. Then a path opens toward thinking about mobile peoples as a political concept

Troubling the exclusive privileges of citizenship: mobile solidarities, asylum seekers, and the right to work

This article discusses asylum seekers and the right to work in the UK. Differential access to the labour market is one of the ways in which the state maintains a distinction between British citizens, who ‘belong’, and non-citizens who do not. While such a policy approach garners widespread support amongst the general public of citizens, it does not go uncontested. This article discusses a UK-based campaign, ‘Let Them Work’, which has sought to influence the government in extending the right to work to asylum seekers. In doing so, it demonstrates the ways in which the stratified regime of citizenship rights is contested politically, and explores how such contestation troubles the exclusive privileges of citizenship by enacting mobile solidarities from marginalised spaces

Social representations and the politics of participation

Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge