The extracellular matrix and the immune system : A mutually dependent relationship

Acknowledgments: We are very grateful to our colleagues at the Wellcome Centre for Cell-Matrix Research and the Lydia Becker Institute for Immunology and Inflammation for many stimulating discussions. We would especially like to thank A. Day, D. Thornton, R. Lennon, A. MacDonald, and T. Hardingham and the anonymous referees for critical review of the manuscript. Figures have been drawn in BioRender. Funding: This work was supported by MRC-UK grant MR/V011235/1 (J.E.A.) and Wellcome Trust grants 106898/A/15/Z (J.E.A.), 218570/Z/19/Z (D.P.D.), and 203128/A/16/Z (T.E.S., D.P.D., and J.E.A.).Peer reviewedPostprin

Mothers behaving badly: chaotic hedonism and the crisis of neoliberal social reproduction

This article focuses on the significance of the plethora of representations of mothers ‘behaving badly’ in contemporary anglophone media texts, including the films Bad Moms, Fun Mom Dinner and Bad Mom’s Christmas, the book and online cartoons Hurrah for Gin and the recent TV comedy dramas Motherland, The Let Down and Catastrophe. All these media texts include representations of, first, mothers in the midst of highly chaotic everyday spaces where any smooth routine of domesticity is conspicuous by its absence; and second, mothers behaving hedonistically, usually through drinking and partying, behaviour that is more conventionally associated with men or women without children. After identifying the social type of the mother behaving badly (MBB), the article locates and analyses it in relation to several different social and cultural contexts. These contexts are: a neoliberal crisis in social reproduction marked by inequality and overwork; the continual if contested role of women as ‘foundation parents’; and the negotiation of longer-term discourses of female hedonism. The title gestures towards a popular British sitcom of the 1990s, Men Behaving Badly, which popularized the idea of the ‘new lad’; and this article suggests that the new lad’s counterpart, the ladette, is mutating into the mother behaving badly, or the ‘lad mom’. Asking what work this figure does now, in a later neoliberal context, it argues that the mother behaving badly is simultaneously indicative of a widening and liberating range of maternal subject positions and symptomatic of a profound contemporary crisis in social reproduction. By focusing on the classed and racialised dynamics of the MBB – by examining who exactly is permitted to be hedonistic, and how – and by considering the MBB’s limited and partial imagining of progressive social change, the article concludes by emphasizing the urgency of creating more connections between such discourses and ‘parents behaving politically’

Managing and monitoring equality and diversity in UK sport: An evaluation of the sporting equals Racial Equality Standard and its impact on organizational change

Despite greater attention to racial equality in sport in recent years, the progress of national sports organizations toward creating equality of outcomes has been limited in the United Kingdom. The collaboration of the national sports agencies, equity organizations and national sports organizations (including national governing bodies of sport) has focused on Equality Standards. The authors revisit an earlier impact study of the Racial Equality Standard in sport and supplement it with another round of interview material to assess changing strategies to manage diversity in British sport. In particular, it tracks the impact on organizational commitment to diversity through the period of the establishment of the Racial Equality Standard and its replacement by an Equality Standard that deals with other diversity issues alongside race and ethnicity. As a result, the authors question whether the new, generic Equality Standard is capable of addressing racial diversity and promoting equality of outcomes. © 2006 Sage Publications

Prime beef cuts : culinary images for thinking 'men'

The paper contributes to scholarship theorising the sociality of the brand in terms of subject positions it makes possible through drawing upon the generative context of circulating discourses, in this case of masculinity, cuisine and celebrity. Specifically, it discusses masculinity as a socially constructed gender practice (Bristor and Fischer, 1993), examining materialisations of such practice in the form of visualisations of social relations as resources for 'thinking gender' or 'doing gender'. The transformative potential of the visualisations is illuminated by exploring the narrative content choreographed within a series of photographic images positioning the market appeal of a celebrity chef through the medium of a contemporary lifestyle cookery book. We consider how images of men 'doing masculinity'are not only channelled into reproducing existing gender hierarchy and compulsory heterosexuality in the service of commercial ends, but also into disrupting such enduring stereotyping through subtle reframing. We acknowledge that masculinity is already inscribed within conventionalised representations of culinary culture. In this case we consider how traces of masculinity are exploited and reinscribed through contemporary images that generate resources for rethinking masculine roles and identities, especially when viewed through the lens of stereotypically feminised pursuits such as shopping, food preparation, cooking, and the communal intimacy of food sharing. We identify unsettling tensions within the compositions, arguing that they relate to discursive spaces between the gendered positions written into the images and the popular imagination they feed off. Set against landscapes of culinary culture, we argue that the images invoke a brand of naively roughish "laddishness" or "blokishness", rendering it in domesticated form not only as benign and containable, but fashionable, pliable and, importantly, desirable. We conclude that although the images draw on stereotypical premeditated notions of a feral, boisterous and untamed heterosexual masculinity, they also set in motion gender-blending narratives

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

Background: The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.Results: Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.Conclusions: HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another

High-Performance Work Systems and Organizational Performance in Emerging Economies: Evidence from MNEs in Turkey

This study examines the association between the usage of high-performance work systems (HPWS) by subsidiaries of multinational enterprises (MNEs) in Turkey and employee and subsidiary level outcomes. The study is based on a survey of 148 MNE subsidiaries operating in Turkey. The results show that the usage of HPWS has a significant positive impact on employee effectiveness. However, their impact on employee skills and development, and organizational financial performance are far less clear. Our findings highlight the extent to which HWPS need to be adapted to take account of context-specific institutional realities. © 2014 Springer-Verlag Berlin Heidelberg

Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors

Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation due to a lack of mechanistic understanding. Specifically, CXCL4 (Platelet Factor 4, PF4) has no established receptor that explains its function. Here, we use biophysical, in vitro, and in vivo techniques to determine the mechanism underlying CXCL4-mediated leukocyte recruitment. We demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars on proteoglycans within the endothelial extracellular matrix, resulting in increased adhesion of leukocytes to the vasculature, increased vascular permeability, and non-specific recruitment of a range of leukocytes. Furthermore, GAG sulfation confers selectivity onto chemokine localization. These findings present mechanistic insights into chemokine biology and provide future therapeutic targets

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl