170 research outputs found

    Tragic but brave or just crips with chips? Songs and their lyrics in the Disability Arts Movement in Britain

    Get PDF
    Disability culture is a site within which social and positional identities are struggled for and dominant discourses rejected; in which mainstream representations of people with impairments – as victims of personal tragedy – are held to the light and revealed as hegemonic constructions within a disabling society. Drawing upon styles that range from jazz, blues and folk to reggae, performance poetry and punk, disabled singers and bands in the Disability Arts Movement in Britain have been central to the development of an affirmative disability discourse rooted in ideas of pride, anger and strength. Examining lyrics by Johnny Crescendo, Ian Stanton and the Fugertivs – performers emerging as part of this movement in the 1980s and 1990s – this article considers the dark humour which runs through much of this work. It is suggested that these lyrics' observational reflections on everyday experiences of being oppressed as disabled people have been overlooked within critical disability studies to date, but are important in developing an understanding of positive disability identity as a tool available to disabled people in order to make sense of, and express themselves within, the world in which they find themselves

    Leukocytes and the Natural History of Deep Vein Thrombosis Current Concepts and Future Directions

    Get PDF
    Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.</jats:p

    Propulsion in cubomedusae : mechanisms and utility

    Get PDF
    © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 8 (2013): e56393, doi:10.1371/journal.pone.0056393.Evolutionary constraints which limit the forces produced during bell contractions of medusae affect the overall medusan morphospace such that jet propulsion is limited to only small medusae. Cubomedusae, which often possess large prolate bells and are thought to swim via jet propulsion, appear to violate the theoretical constraints which determine the medusan morphospace. To examine propulsion by cubomedusae, we quantified size related changes in wake dynamics, bell shape, swimming and turning kinematics of two species of cubomedusae, Chironex fleckeri and Chiropsella bronzie. During growth, these cubomedusae transitioned from using jet propulsion at smaller sizes to a rowing-jetting hybrid mode of propulsion at larger sizes. Simple modifications in the flexibility and kinematics of their velarium appeared to be sufficient to alter their propulsive mode. Turning occurs during both bell contraction and expansion and is achieved by generating asymmetric vortex structures during both stages of the swimming cycle. Swimming characteristics were considered in conjunction with the unique foraging strategy used by cubomedusae.This work was supported by an ONR MURI award (N000140810654) and National Science Foundation grant OCE 0623508 to JHC, SPC, JOD. And the work was supported by the Roger Williams University Foundation to Promote Scholarship

    Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

    Get PDF
    Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK092760)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK49216)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant U54DK110805)National Heart, Lung, and Blood Institute (Grant UO1-HL100001)National Heart, Lung, and Blood Institute (Grant U01HL134812)National Heart, Lung, and Blood Institute (Grant R01HL04880)National Institutes of Health (U.S.) (Grant R24OD017870-01

    Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

    Get PDF
    Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, Pless than0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.Funding Agencies|European Commission [QLG1-CT-2002-00896]; Swedish Heart-Lung Foundation; Swedish Research Council [8691, 0593]; Knut and Alice Wallenberg Foundation; Foundation for Strategic Research; Stockholm County Council [592229]; Karolinska Institutet; Stockholm County Council; European Union Framework Programme 7 for the Innovative Medicine Initiative [IMI/115006]; Academy of Finland [110413]; British Heart Foundation [RG2008/08, RG2008/014]; Italian Ministry of Health (Ricerca Corrente); Uppsala University; Uppsala University Hospital; Swedish Research Council for Infrastructures; Swedish Heart-Lung Foundation [20120600, 20130399]; Tore Nilsson foundation; Gamla Tjanarinnor foundation; Thurings foundation; Stiftelsen for Gamla Tjanarinnor; Ake Wiberg foundation; Tore Nilssons foundation; Magnus Bergvall Foundation; Foundation for Old Servants; Ministry of Education and Culture in Finland; Vasterbotten County Council; Swedish Heart and Lung Foundation; National Excellence Program [TAMOP 4.2.4.A/1-11-1-2012-0001]; European Union; European Social Fund; UK Medical Research Council [K013351]; Economic and Social Research Council; Academy of Finland; University College London Genetics Institute</p

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

    Get PDF
    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor

    Get PDF
    Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases
    corecore