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Nitric oxide (NO) is an important regulator of Na+ reabsorption by pulmonary epithelial cells and therefore of alveolar fluid clearance. The mechanisms by which NO affects epithelial ion transport are poorly understood and vary from model to model. In this study, the effects of NO on sodium reabsorption by H441 cell monolayers were studied in an Ussing chamber. Two NO donors, (Z)-1-[N-(3-aminopropyl)-N-(n-propyl) amino]diazen-1-ium-1,2-diolate and diethylammonium(Z)-1-(N, N-diethylamino) diazen-1-ium-1,2-diolate, rapidly, reversibly, and dose-dependently reduced amiloride-sensitive, short-circuit currents across H441 cell monolayers. This effect was neutralized by the NO scavenger hemoglobin and was not observed with inactive NO donors. The effects of NO were not blocked by 8-bromoguanosine-3',5'-cyclic monophosphate or by soluble guanylate cyclase inhibitors (methylene blue and 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) and were therefore independent of soluble guanylate cyclase signaling. NO targeted apical, highly selective, amiloride-sensitive Na+ channels in basolaterally permeabilized H441 cell monolayers. NO had no effect on the activity of the human epithelial sodium channel heterologously expressed in Xenopus oocytes. NO decreased Na+/K+-ATPase activity in apically permeabilized H441 cell monolayers. The inhibition of Na+/K+-ATPase activity by NO was reversed by mercury and was mimicked by N-ethylmaleimide, which are agents that reverse and mimic, respectively, the reaction of NO with thiol groups. Consistent with these data, S-NO groups were detected on the Na+/K+-ATPase a subunit in response to NO-donor application, using a biotin-switch approach coupled to a Western blot. These data demonstrate that, in the H441 cell model, NO impairs Na+ reabsorption by interfering with the activity of highly selective Na+ channels and the Na+/K+-ATPase.
The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.
Routing Attacks are a serious threat to communication in tactical MANETs. TOGBAD is a centralised approach, using topology graphs to detect such attacks. In this paper, we present TOGBAD's newly added wormhole detection capability. It is an adaptation of a wormhole detection method developed by Hu et al. This method is based on nodes' positions. We adapted it to the specific properties of tactical environments. Furthermore, we present simulation results which show TOGBAD's performance regarding the detection of wormhole attacks.
NMR structures of thiostrepton derivatives for characterization of the ribosomal binding site
(2011)
In an explorative study, we investigated on German schoolteachers how they use, reuse, produce and manage Open Educational Resources. The main questions in this research have been, what their motivators and barriers are in their use of Open Educational Resources, what others can learn from their Open Educational Practices, and what we can do to raise the dissemination level of OER in schools.
Adaptability as a Special Demand on Open Educational Resources: The Cultural Context of e-Learning
(2011)
Producing and providing Open Educational Resources (OERs) is driven by the concepts of openness and sharing. Although there already are a lot of free high-quality resources available, practitioners often rather rewrite learning resources than creatively embed (and thus, reuse) existing OERs. In this paper, we analyse the reasons for this in two different educational contexts. As a result of this analysis, we found that the uncertainty on possible adaptation needs is one of the major barriers. In order to overcome this barrier and make different learning contexts comparable, we analysed the context of learners and in particular, in the research project ‘Learning Culture’, we investigated the field of culturally motivated expectations and attitudes of learners. This paper shows the results of this research project and discusses which cultural issues should be taken into consideration when OERs are to be adapted from one to another cultural context.