1,122 research outputs found

    The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease

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    AbstractChronic lung disease remains the major cause of morbidity and mortality of cystic fibrosis (CF) patients. Cftr mutant mice developed severe intestinal obstruction, but did not exhibit the characteristic CF ion transport defects (i.e. deficient cAMP-dependent Cl− secretion and increased Na+ absorption) in the lower airways, and failed to develop CF-like lung disease. These observations led to the generation of transgenic mice with airway-specific overexpression of the epithelial Na+ channel (ENaC) as an alternative approach to mimic CF ion transport pathophysiology in the lung. Studies of the phenotype of βENaC-transgenic mice demonstrated that increased airway Na+ absorption causes airway surface liquid (ASL) depletion, reduced mucus transport and a spontaneous CF-like lung disease with airway mucus obstruction and chronic airway inflammation. Here, we summarize approaches that can be applied for studies of the complex in vivo pathogenesis and preclinical evaluation of novel therapeutic strategies in this model of CF lung disease

    Troubling stories of the end of occupy : feminist narratives of betrayal at occupy Glasgow

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    This article offers a feminist take on the question of why Occupy camps closed down, in the form of a narrative analysis of interviews from participants in Occupy Glasgow. In response to the emergence of an activist discourse emphasising the role of external forces in camp closure and the existence of a longer-term legacy in terms of individual and community politicisation, I build here on feminist interventions that point instead to serious internal problems within the camps and thus to a more limited legacy. Interrogating the plotting, characterisation and denouement of interviewee narratives, I show that feminist participants in Occupy Glasgow characterise the trajectory of the camp as a tragedy, attribute responsibility for the camp’s demise to co-campers and sometimes to themselves, and present the outcome of Occupy Glasgow as limited, and in some cases even traumatic. This raises serious questions about the culmination and outcomes of Occupy in Glasgow and more generally, and indicates the extent of the hard work remaining if future mobilisation against neoliberal austerity is to be more inclusive and sustainable. The article closes by considering the theoretical implications for the wider question of why movements come to an end

    Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

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    Recent evidence suggests that inadequate hydration of airway surfaces is a common mechanism in the pathogenesis of airway mucus obstruction. Inhaled hypertonic saline (HS) induces osmotic water flux, improving hydration of airway surfaces. However, trials in patients with obstructive lung diseases are limited. The aim of this study was to investigate effects of HS on mucus obstruction and airway inflammation in the prevention and treatment of obstructive lung disease in vivo. We, therefore, used the β-epithelial Na+ channel (βENaC)–overexpressing mouse as a model of chronic obstructive lung disease and determined effects of preventive and late therapy with 3% HS and 7% HS on pulmonary mortality, airway mucus obstruction, and inflammation. We found that preventive treatment with 3% HS and 7% HS improved growth, reduced mortality, and reduced mucus obstruction in neonatal βENaC-overexpressing mice. In adult βENaC-overexpressing mice with chronic lung disease, mucus obstruction was significantly reduced by 7% HS, but not by 3% HS. Treatment with HS triggered airway inflammation with elevated keratinocyte chemoattractant levels and neutrophils in airways from wild-type mice, but reduced keratinocyte chemoattractant in chronic neutrophilic inflammation in adult βENaC-overexpressing mice. Our data demonstrate that airway surface rehydration with HS provides an effective preventive and late therapy of mucus obstruction with no consistent effects on inflammation in chronic lung disease. These results suggest that, through mucokinetic effects, HS may be beneficial for patients with a spectrum of obstructive lung diseases, and that additional strategies are required for effective treatment of associated airway inflammation

    How brains make decisions

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    This chapter, dedicated to the memory of Mino Freund, summarizes the Quantum Decision Theory (QDT) that we have developed in a series of publications since 2008. We formulate a general mathematical scheme of how decisions are taken, using the point of view of psychological and cognitive sciences, without touching physiological aspects. The basic principles of how intelligence acts are discussed. The human brain processes involved in decisions are argued to be principally different from straightforward computer operations. The difference lies in the conscious-subconscious duality of the decision making process and the role of emotions that compete with utility optimization. The most general approach for characterizing the process of decision making, taking into account the conscious-subconscious duality, uses the framework of functional analysis in Hilbert spaces, similarly to that used in the quantum theory of measurements. This does not imply that the brain is a quantum system, but just allows for the simplest and most general extension of classical decision theory. The resulting theory of quantum decision making, based on the rules of quantum measurements, solves all paradoxes of classical decision making, allowing for quantitative predictions that are in excellent agreement with experiments. Finally, we provide a novel application by comparing the predictions of QDT with experiments on the prisoner dilemma game. The developed theory can serve as a guide for creating artificial intelligence acting by quantum rules.Comment: Latex file, 20 pages, 3 figure

    Expanding the Taxonomy of (Mis-)Recognition in the Economic Sphere

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    This paper makes a contribution to debates in recognition theory by expanding the taxonomy of (mis-)recognition in the economic sphere. We argue that doing justice to the variety of ways in which recognition is engaged in economic relationships requires: (1) to take into consideration not just the recognition principle of esteem, but also (various aspects of) need and respect; (2) to distinguish a productive from a consumptive dimension with regards to each principle of recognition (need, esteem and respect); (3) and to identify the specific economic relationship at stake (e.g. between consumers and producers, or between employers and employees). In this way, we can account for the diversity of demands for recognition made in the economic sphere, explain what underpins them, and bring structure into these diverse phenomena. What is more, our expanded taxonomy is a useful tool for social pathology theorists. They have to appreciate the full range of variants of misrecognition when diagnosing pathologies of misrecognition in the economic sphere
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