Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance.

Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.Support was provided by the Wellcome Trust (A.C.H., J.L.H., G.R) and Cancer Research UK (A.C.H.), Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust (L.A.-D.; A.C.H.); Marie Curie and EMBO fellowships (M.S.).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150519/ncomms8090/full/ncomms8090.html

Disability activism and the politics of scale

In this paper, we examine the role of spatial scale in mediating and shaping political struggles between disabled people and the state. Specifically, we draw on recent theoretical developments concerning the social construction of spatial scale to interpret two case studies of disability activism within Canada and Ireland. In particular, we provide an analysis of how successful the disability movement in each locale has been at 'jumping scale' and enacting change, as well as examining what the consequences of such scaling-up have been for the movement itself. We demonstrate that the political structures operating in each country markedly affect the scaled nature of disability issues and the effectiveness of political mobilization at different scales

Constituting Citizenship Through the Emotions: Singaporean Transmigrants in London

10.1080/00045600903102857Annals of the Association of American Geographers994788-80

Postcolonial manifestations of African spatiality in Europe : the invisible 'public' spaces of Ghent

The focus of this chapter is on everyday spaces of African migration in the mid-sized city of Ghent. One manifestation of African spatiality is discussed in-depth in relation to its (in)visibility and publicity: an African shop located in an ordinary terraced house. With no less than 12 activities taking place in the building, the shop is rather a “public” place than solely a space of commercial transactions, although this is not signaled in very visible ways. By analyzing the modest stylistic appropriations of the façade and the significant re-arrangements of the buildings’ interior spaces that challenge more conventional usages of spaces in Ghent’s ordinary houses, this chapter puts this African shop to the fore as emblematic of how the process of materialization of transnational lifestyles and connections is always a balancing act between the visibility necessary for functioning as a (semi-)pubic place and the invisibility required to circumvent hegemonic regulatory regimes

The Cytoplasmic Location of Chicken Mx Is Not the Determining Factor for Its Lack of Antiviral Activity

Chicken Mx belongs to the Mx family of interferon-induced dynamin-like GTPases, which in some species possess potent antiviral properties. Conflicting data exist for the antiviral capability of chicken Mx. Reports of anti-influenza activity of alleles encoding an Asn631 polymorphism have not been supported by subsequent studies. The normal cytoplasmic localisation of chicken Mx may influence its antiviral capacity. Here we report further studies to determine the antiviral potential of chicken Mx against Newcastle disease virus (NDV), an economically important cytoplasmic RNA virus of chickens, and Thogoto virus, an orthomyxovirus known to be exquisitely sensitive to the cytoplasmic MxA protein from humans. We also report the consequences of re-locating chicken Mx to the nucleus.Chicken Mx was tested in virus infection assays using NDV. Neither the Asn631 nor Ser631 Mx alleles (when transfected into 293T cells) showed inhibition of virus-directed gene expression when the cells were subsequently infected with NDV. Human MxA however did show significant inhibition of NDV-directed gene expression. Chicken Mx failed to inhibit a Thogoto virus (THOV) minireplicon system in which the cytoplasmic human MxA protein showed potent and specific inhibition. Relocalisation of chicken Mx to the nucleus was achieved by inserting the Simian Virus 40 large T antigen nuclear localisation sequence (SV40 NLS) at the N-terminus of chicken Mx. Nuclear re-localised chicken Mx did not inhibit influenza (A/PR/8/34) gene expression during virus infection in cell culture or influenza polymerase activity in A/PR/8/34 or A/Turkey/50-92/91 minireplicon systems.The chicken Mx protein (Asn631) lacks inhibitory effects against THOV and NDV, and is unable to suppress influenza replication when artificially re-localised to the cell nucleus. Thus, the natural cytoplasmic localisation of the chicken Mx protein does not account for its lack of antiviral activity

A perspective on radical transformations to sustainability: resistances, movements and alternatives

A transformation to sustainability calls for radical and systemic societal shifts. Yet what this entails in practice and who the agents of this radical transformation are require further elaboration. This article recenters the role of environmental justice movements in transformations, arguing that the systemic, multi-dimensional and intersectional approach inherent in EJ activism is uniquely placed to contribute to the realization of equitable sustainable futures. Based on a perspective of conflict as productive, and a “conflict transformation” approach that can address the root issues of ecological conflicts and promote the emergence of alternatives, we lay out a conceptual framework for understanding transformations through a power analysis that aims to confront and subvert hegemonic power relations; that is, multi-dimensional and intersectional; balancing ecological concerns with social, economic, cultural and democratic spheres; and is multi-scalar, and mindful of impacts across place and space. Such a framework can help analyze and recognize the contribution of grassroots EJ movements to societal transformations to sustainability and support and aid radical transformation processes. While transitions literature tends to focus on artifacts and technologies, we suggest that a resistance-centred perspective focuses on the creation of new subjectivities, power relations, values and institutions. This recenters the agency of those who are engaged in the creation and recuperation of ecological and new ways of being in the world in the needed transformation

The Role of Host Genetics in Susceptibility to Influenza: A Systematic Review

Background: The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380). Methods and Findings: PubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven. Conclusion: The fundamental question ‘‘Is susceptibility to severe influenza in humans heritable?’ ’ remains unanswered. No

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage