45 research outputs found

    Modulation of human airway barrier functions during Burkholderia thailandensis and Francisella tularensis Infection: Running Title: Airway Barrier Functions during Bacterial Infections

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    The bronchial epithelium provides protection against pathogens from the inhaled environment through the formation of a highly-regulated barrier. In order to understand the pulmonary diseases melioidosis and tularemia caused by Burkholderia thailandensis and Fransicella tularensis, respectively, the barrier function of the human bronchial epithelium were analysed. Polarised 16HBE14o- or differentiated primary human bronchial epithelial cells (BECs) were exposed to increasing multiplicities of infection (MOI) of B. thailandensis or F. tularensis Live Vaccine Strain and barrier responses monitored over 24–72 h. Challenge of polarized BECs with either bacterial speciescaused an MOI- and time-dependent increase in ionic permeability, disruption of tight junctions, and bacterial passage from the apical to the basolateral compartment. B. thailandensis was found to be more invasive than F. tularensis. Both bacterial species induced an MOI-dependent increase in TNF-α release. An increase in ionic permeability and TNF-α release was induced by B. thailandensis in differentiated BECs. Pretreatment of polarised BECs with the corticosteroid fluticasone propionate reduced bacterial-dependent increases in ionic permeability, bacterial passage, and TNF-α release.TNF blocking antibody Enbrel® reduced bacterial passage only. BEC barrier properties are disrupted during respiratory bacterial infections and targeting with corticosteroids or anti-TNF compounds may represent a therapeutic option

    Voicing passion: The emotional economy of songwriting

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    This article examines articulations of the role of passion in accounts of the life and work of the songwriter. It draws upon a range of interviews with successful artists captured in the Sodajerker On Songwriting podcast. It is suggested that these interviews capture the ‘voicing’ of the conventions of creativity in popular music, exploring a context in which passionate motivation, expression and understanding of the (potentially) affective responses to songs are paramount to the labour of the songwriter. The article explores how the core of this labour deals in emotion, attempting to articulate feelings in recognisable, tradable form. This is a process that is both instrumentally rationalised but often felt to be a deeply authentic process, understood (and believed) to spring from the individual’s emotional experience, so conferring identity in a generic field. In light of current debates about the nature of creative work and emotional labour, the accounts drawn upon here can be seen to epitomise many of the qualities of what constitutes ‘good work’ through a mode of self-actualisation

    Conceptualizing Creativity and Strategy in the Work of Professional Songwriters

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    Drawing upon interviews conducted as part of the Sodajerker on Songwriting podcast this paper explores professional songwriting as musical labor. It explores how songwriters conceptualize creativity and what strategies they employ for the delivery of original songs. It argues that individuals evince a faith in their own autonomy in the face of the demands of form and industry, expressing intuitive concepts of inspiration and practical insights into the nature of their work as work. The paper suggests that achieving and maintaining success is affirmed in a conjunction of value that is both economic and aesthetic, personal and public

    Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

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    Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research
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