Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.

Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.Medical Research Council (G0900424, ER), the March of Dimes (5-FY11-119, ER), the Wellcome Trust (093029, ER), Newton Trust (14.07h, ER), Wellcome Trust PhD programme for Clinicians (MN), Postdoctoral Fellowship from the Government of the Basque Country (UL), MRC studentship (RVR), British Heart Foundation Studentship (EJB), COST BM1201. Core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).This is the final version of the article. It first appeared from the Company of Biologists at http://dx.doi.org/10.1242/dev.134023

Digital realities & virtual ideals: Portraiture, idealism and the clash of subjectivities in the post-digital era

This is an accepted manuscript of an article published by Taylor and Francis in Photography and Culture on 26/02/2019, available online: https://doi.org/10.1080/17514517.2019.1565290 The accepted version of the publication may differ from the final published version.All portraits play host to a number of antithetical tensions, such as ‘private’ and ‘public’, ‘real’ and ‘ideal’, without which they would be reduced to a type of unassuming identification of subjects. Whereas in premodern times the artist was subject to the demands of the commissioner, after modernism the representational desires of the sitter began to clash with the creative intentions of the artist. Prior to the introduction of digital formats, this clash of subjectivities manifests itself in photography during the production of the work, the shooting of a portrait. Digital photography and post-production editing have expanded the methods for idealising external appearance; a desire stimulated by the recent technological acceleration of production and circulation of more ‘manipulated’ portraits than ever. In what ways, therefore, does the introduction of digital post-production editing and composite images affect this double-clash in portraiture, between the real and ideal, and the desires of the sitter against the intentions of the artist? Moreover, how does the evolution of self-portraiture in the ‘selfie’ affect the epistemological character of the genre? As such, is conceptual and aesthetic subservience a matter of technological possibility or creative determination

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

Awards, Archives, and Affects: Tropes in the World Press Photo Contest 2009 - 2011

__Abstract__ Photography contests have assumed an increasingly significant public role in the context of the global surge of mass-mediated war reporting. This study focuses on the recurrence of visual tropes in press photographs awarded in the annual contest World Press Photo (WPP) in the years 2009–11. By tropes, we mean conventions (e.g. a mourning woman, a civilian facing soldiers, a distressed witness to an atrocity) that remain unchanged despite their travels across the visual sphere, gaining professional and public recognition and having a strong affective impact. We contend that photography contests such as the WPP influence and organize a process of generic understanding of war, disaster and atrocity that is based on a number of persistent tropes, such as the mourner, the protester or the survivor amidst chaos and ruins. We further show that these tropes are gendered along traditional conceptions of femininity and masculinity, appealing strongly to both judges and wider audiences. The evidence for our claim comes from an analysis of the photographs that won awards, observation of the judging sessions, semi-structured interviews with three jury chairmen, and public commentary on the juries’ choices (blogs, newspapers and websites)

A sack in the sand: Photography in the age of information

Throughout the 1990s the relationship between culture and technology was sharply focused in a debate about whether digital technologies signalled the death or radical displacement of photography. The case for the cultural continuity of photography centred upon a rejection of a strong form of technological determinism. It is now clear that far from being displaced to the margins of culture, there is now more photography than ever. There have also been dramatic developments: mobile phone manufacturers have put more cameras into people's hands then ever before; the photograph as social document and historical witness persists but in changing ways; photographs circulate globally on an unprecedented scale via electronic image banks. It is clear that such changes and developments do involve new technologies. However, rather than being due to the kind of technological determinism debated earlier, this is because photography has come to exist within a new technological environment. In many recent accounts, 'information' and information technology are repeatedly cited as constituting a new and shaping context for photographic practices. This article offers a conceptual framework for thinking about these changes by relating tendencies in contemporary discussions of photography to another discourse and another set of practices: informatics. Copyright © 2007 Sage Publications

Our Relationship with the Image as a Form of Being-With

This paper looks at the development of the artistic work from a narrative work into an experiential one. How the presentation of sublime in art has moved us away from finding meaning in narrative into taking on meaning through facing our relationship to the other. It traces how this change in communication has meant that the viewer’s experience with a work is the work. It takes an historical and theoretical perspective before discussing a proposed project, The Lamps of Presence, as a work employing these theories