Amiloride-Sensitive Sodium Channels and Pulmonary Edema

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

Why Do We have to Move Fluid to be Able to Breathe?

The ability to breathe air represents a fundamental step in vertebrate evolution that was accompanied by several anatomical and physiological adaptations. The morphology of the air-blood barrier is highly conserved within air-breathing vertebrates. It is formed by three different plies, which are represented by the alveolar epithelium, the basal lamina, and the endothelial layer. Besides these conserved morphological elements, another common feature of vertebrate lungs is that they contain a certain amount of fluid that covers the alveolar epithelium. The volume and composition of the alveolar fluid is regulated by transepithelial ion transport mechanisms expressed in alveolar epithelial cells. These transport mechanisms have been reviewed extensively. Therefore, the present review focuses on the properties and functional significance of the alveolar fluid. How does the fluid enter the alveoli? What is the fate of the fluid in the alveoli? What is the function of the alveolar fluid in the lungs? The review highlights the importance of the alveolar fluid, its volume and its composition. Maintenance of the fluid volume and composition within certain limits is critical to facilitate gas exchange. We propose that the alveolar fluid is an essential element of the air-blood barrier. Therefore, it is appropriate to refer to this barrier as being formed by four plies, namely (1) the thin fluid layer covering the apical membrane of the epithelial cells, (2) the epithelial cell layer, (3) the basal membrane, and (4) the endothelial cells

Accurate Judgment by Dementia Patients of Neutral Faces with Respect to Trustworthiness and Valence

The present study investigates whether dementia patients can make accurate social and affective judgments of face stimuli. We used verbal material as a control condition to see whether dementia patients are capable of using the rating scales the same way as controls. We compared the trustworthiness, valence, and arousal ratings of dementia patients with those from a healthy control group. Participants rated pictures of young and old, female and male neutral faces and two fictitious biographies. The results indicate that dementia patients make accurate judgments of unfamiliar faces with respect to trustworthiness and valence. Results concerning arousal ratings suggest that the corresponding scale might be difficult to use for dementia patients and possibly for older participants as well

Concepts in hypoxia reborn

The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies

Neither dust nor black carbon causing apparent albedo decline in Greenland\u27s dry snow zone: Implications for MODIS C5 surface reflectance

Remote sensing observations suggest Greenland ice sheet (GrIS) albedo has declined since 2001, even in the dry snow zone. We seek to explain the apparent dry snow albedo decline. We analyze samples representing 2012–2014 snowfall across NW Greenland for black carbon and dust light-absorbing impurities (LAI) and model their impacts on snow albedo. Albedo reductions due to LAI are small, averaging 0.003, with episodic enhancements resulting in reductions of 0.01–0.02. No significant increase in black carbon or dust concentrations relative to recent decades is found. Enhanced deposition of LAI is not, therefore, causing significant dry snow albedo reduction or driving melt events. Analysis of Collection 5 Moderate Resolution Imaging Spectroradiometer (MODIS) surface reflectance data indicates that the decline and spectral shift in dry snow albedo contains important contributions from uncorrected Terra sensor degradation. Though discrepancies are mostly below the stated accuracy of MODIS products, they will require revisiting some prior conclusions with C6 data

Incipient fault detection study for advanced spacecraft systems

A feasibility study to investigate the application of vibration monitoring to the rotating machinery of planned NASA advanced spacecraft components is described. Factors investigated include: (1) special problems associated with small, high RPM machines; (2) application across multiple component types; (3) microgravity; (4) multiple fault types; (5) eight different analysis techniques including signature analysis, high frequency demodulation, cepstrum, clustering, amplitude analysis, and pattern recognition are compared; and (6) small sample statistical analysis is used to compare performance by computation of probability of detection and false alarm for an ensemble of repeated baseline and faulted tests. Both detection and classification performance are quantified. Vibration monitoring is shown to be an effective means of detecting the most important problem types for small, high RPM fans and pumps typical of those planned for the advanced spacecraft. A preliminary monitoring system design and implementation plan is presented

Automatic Detection of GUI Design Smells: The Case of Blob Listener

International audienceGraphical User Interfaces (GUIs) intensively rely on event-driven programming: widgets send GUI events, which capture users' interactions, to dedicated objects called controllers. Controllers implement several GUI listeners that handle these events to produce GUI commands. In this work, we conducted an empirical study on 13 large Java Swing open-source software systems. We study to what extent the number of GUI commands that a GUI listener can produce has an impact on the change-and fault-proneness of the GUI listener code. We identify a new type of design smell, called Blob listener that characterizes GUI listeners that can produce more than two GUI commands. We show that 21 % of the analyzed GUI controllers are Blob listeners. We propose a systematic static code analysis procedure that searches for Blob listener that we implement in InspectorGuidget. We conducted experiments on six software systems for which we manually identified 37 instances of Blob listener. InspectorGuidget successfully detected 36 Blob listeners out of 37. The results exhibit a precision of 97.37 % and a recall of 97.59 %. Finally, we propose coding practices to avoid the use of Blob listeners

Thyroid hormone-regulated gene expression in juvenile mouse liver: identification of thyroid response elements using microarray profiling and in silico analyses

<p>Abstract</p> <p>Background</p> <p>Disruption of thyroid hormone signalling can alter growth, development and energy metabolism. Thyroid hormones exert their effects through interactions with thyroid receptors that directly bind thyroid response elements and can alter transcriptional activity of target genes. The effects of short-term thyroid hormone perturbation on hepatic mRNA transcription in juvenile mice were evaluated, with the goal of identifying genes containing active thyroid response elements. Thyroid hormone disruption was induced from postnatal day 12 to 15 by adding goitrogens to dams' drinking water (hypothyroid). A subgroup of thyroid hormone-disrupted pups received intraperitoneal injections of replacement thyroid hormones four hours prior to sacrifice (replacement). An additional group received only thyroid hormones four hours prior to sacrifice (hyperthyroid). Hepatic mRNA was extracted and hybridized to Agilent mouse microarrays.</p> <p>Results</p> <p>Transcriptional profiling enabled the identification of 28 genes that appeared to be under direct thyroid hormone-regulation. The regulatory regions of the genome adjacent to these genes were examined for half-site sequences that resemble known thyroid response elements. A bioinformatics search identified 33 thyroid response elements in the promoter regions of 13 different genes thought to be directly regulated by thyroid hormones. Thyroid response elements found in the promoter regions of Tor1a, 2310003H01Rik, Hect3d and Slc25a45 were further validated by confirming that the thyroid receptor is associated with these sequences <it>in vivo </it>and that it can bind directly to these sequences <it>in vitro</it>. Three different arrangements of thyroid response elements were identified. Some of these thyroid response elements were located far up-stream (> 7 kb) of the transcription start site of the regulated gene.</p> <p>Conclusions</p> <p>Transcriptional profiling of thyroid hormone disrupted animals coupled with a novel bioinformatics search revealed new thyroid response elements associated with genes previously unknown to be responsive to thyroid hormone. The work provides insight into thyroid response element sequence motif characteristics.</p

Evaluation of Rodent Spaceflight in the NASA Animal Enclosure Module for an Extended Operational Period (up to 35 days)

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting for shuttle flight missions, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats