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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.
The vectorial transport of Na+ across epithelia is crucial for the maintenance of Na+ and water homeostasis in organs such as the kidneys, lung, or intestine. Dysregulated Na+ transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, or intestinal disorders, which indicate that a precise regulation of epithelial Na+ transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence which indicates that gasotransmitters may also regulate Na+ transport across epithelia. This review will summarize the available data concerning NO, CO, and H2S dependent regulation of epithelial Na+ transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na+ transport biology.
Wesch D, Althaus M, Miranda P, Cruz-Muros I, Fronius M, Gonzalez-Hernandez T, Clauss WG, de la Rosa DA, Giraldez T. Differential N termini in epithelial Na+ channel delta-subunit isoforms modulate channel trafficking to the membrane. Am J Physiol Cell Physiol 302: C868-C879, 2012. First published December 7, 2011; doi: 10.1152/ajpcell.00255.2011.-The epithelial Na+ channel (ENaC) is a heteromultimeric ion channel that plays a key role in Na+ reabsorption across tight epithelia. The canonical ENaC is formed by three analogous subunits, alpha, beta, and gamma. A fourth ENaC subunit, named delta, is expressed in the nervous system of primates, where its role is unknown. The human delta-ENaC gene generates at least two splice isoforms, delta(1) and delta(2), differing in the N-terminal sequence. Neurons in diverse areas of the human and monkey brain differentially express either delta(1) or delta(2), with few cells coexpressing both isoforms, which suggests that they may play specific physiological roles. Here we show that heterologous expression of delta(1) in Xenopus oocytes and HEK293 cells produces higher current levels than delta(2). Patch-clamp experiments showed no differences in single channel current magnitude and open probability between isoforms. Steady-state plasma membrane abundance accounts for the dissimilarity in macroscopic current levels. Differential trafficking between isoforms is independent of beta- and gamma-subunits, PY-motif-mediated endocytosis, or the presence of additional lysine residues in delta(2)-N terminus. Analysis of delta(2)-N terminus identified two sequences that independently reduce channel abundance in the plasma membrane. The delta(1) higher abundance is consistent with an increased insertion rate into the membrane, since endocytosis rates of both isoforms are indistinguishable. Finally, we conclude that delta-ENaC undergoes dynamin-independent endocytosis as opposed to alpha beta gamma-channels.
The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells
(2012)
BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H(2) S) on Na(+) absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H(2)S were further investigated on Na(+) channels expressed in Xenopus oocytes and Na(+) /K(+)-ATPase activity in vitro. Membrane abundance of Na(+) /K(+)-ATPase was determined by surface biotinylation and Western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca(2+) concentrations were measured with Fura-2. KEY RESULTS H(2)S rapidly and reversibly inhibited Na(+) transport in all the models employed. H(2)S had no effect on Na(+) channels, whereas it decreased Na(+) /K(+)-ATPase currents. H(2)S did not affect the membrane abundance of Na(+) /K(+)-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H(2)S inhibited basolateral calcium-dependent K(+) channels, which consequently decreased Na(+) absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H(2) S impairs pulmonary transepithelial Na(+) absorption, mainly by inhibiting basolateral Ca(2+)-dependent K(+) channels. These data suggest that the H(2)S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na(+) transport.
Malware is responsible for massive economic damage. Being the preferred tool for digital crime, botnets are becoming increasingly sophisticated, using more and more resilient, distributed infrastructures based on peer-to-peer (P2P) protocols. On the other side, current investigation techniques for malware and botnets on a technical level are time-consuming and highly complex. Fraunhofer FKIE is addressing this problem, researching new ways of intelligent process automation and information management for malware analysis in order to minimize the time needed to investigate these threats.
Today’s computer systems face a vast array of severe threats that are posed by automated attacks performed by malicious software as well as manual attacks by individual humans. These attacks not only differ in their technical implementation but may also be location-dependent. Consequentially, it is necessary to join the information from heterogeneous and distributed attack sensors in order to acquire comprehensive information on current ongoing cyber attacks.
Development and Validation of a Rapid and Reliable Method for TPMT Genotyping using real-time PCR
(2012)
Education is widely seen as an important means of addressing both national and international problems, such as political or religious extremism, poverty, and hunger. However, if developing countries are to become societies that can compete properly with Western industrialized countries, not only is a fundamental shift in thinking with regard to the value of education and more/better provision of teaching required, but strong support from other countries is needed as well. This article explores questions such as whether Western policymakers can avoid a repetition of some of the failures of the past few decades in terms of providing foreign aid; how educators and providers of educational scenarios and learning contents can foster and manage the creation of a worldwide knowledge society; and in particular, if the provision of open educational resources (OER) can realistically overcome the educational gap and foster educational justice.
Disorders of the degradation of branched chain amino acids: what is new in clinics and laboratories?
(2012)
Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by severe and progressive neurological damage mainly caused by the loss of sulfite oxidase activity. Elevated urinary levels of sulfite, thiosulfate, and S-sulfocysteine (SSC) are hallmarks in the diagnosis of MoCD and sulfite oxidase deficiency (SOD). Recently, a first successful treatment of a human MoCD type A patient based on a substitution therapy with the molybdenum cofactor precursor cPMP has been reported, resulting in nearly complete normalization of MoCD biomarkers. Knowing the rapid progression of the disease symptoms in nontreated patients, an early diagnosis of MoCD as well as a sensitive method to monitor daily changes in SSC levels, a key marker of sulfite toxicity, is crucial for treatment outcome. Here, we describe a fast and sensitive method for the analysis of SSC in human urine samples using high performance liquid chromatography (HPLC). The analysis is based on precolumn derivatization with O-phthaldialdehyde (OPA) and separation on a C18 reverse phase column coupled to UV detection. The method was extended to human serum analysis and no interference with endogenous amino acids was found. Finally, SSC values from 45 pediatric urine, 75 adult urine, and 24 serum samples from control individuals as well as MoCD patients are reported. Our method represents a cost-effective technique for routine diagnosis of MoCD and SOD, and can be used also to monitor treatment efficiency in those sulfite toxicity disorders on a daily basis.
The osmolality of nonionic, iodinated contrast agents as an important factor for renal safety
(2012)
Software testing in web services environment faces different challenges in comparison with testing in traditional software environments. Regression testing activities are triggered based on software changes or evolutions. In web services, evolution is not a choice for service clients. They have always to use the current updated version of the software. In addition test execution or invocation is expensive in web services and hence providing algorithms to optimize test case generation and execution is vital. In this environment, we proposed several approach for test cases' selection in web services' regression testing. Testing in this new environment should evolve to be included part of the service contract. Service providers should provide data or usage sessions that can help service clients reduce testing expenses through optimizing the selected and executed test cases.
Oft wird die Gewinnung von Gastärzten aus dem Ausland als Möglichkeit zur kurz- und mittelfristigen Deckung des Ärztebedarfs in Kliniken in Erwägung gezogen. Die hohen Anforderungen von Landesprüfungsämtern, Arbeitsagenturen, Ausländerbehörden und Botschaften erweisen sich sowohl für Ärzte als auch Kliniken als schwer überwindbare Hürden. Insbesondere Sprachschwierigkeiten sowie mangelhafte fachliche und kulturelle Kenntnisse der internationalen Ärzte sind ohne professionelle Unterstützung kaum zu kompensieren.
In a research project funded by the German Research Foundation, meteorologists, data publication experts, and computer scientists optimised the publication process of meteorological data and developed software that supports metadata review. The project group placed particular emphasis on scientific and technical quality assurance of primary data and metadata. At the end, the software automatically registers a Digital Object Identifier at DataCite. The software has been successfully integrated into the infrastructure of the World Data Center for Climate, but a key was to make the results applicable to data publication processes in other sciences as well.
The criteria for assessing the quality of rubber materials are the polymer or copolymer composition and the additives. These additives include plasticizers, extender oils, carbon black, inorganic fillers, antioxidants, heat and light stabilizers, processing aids, cross-linking agents, accelerators, retarders, adhesives, pigments, smoke and flame retardants, and others. Determination of additives in polymers or copolymers generally requires the extraction of these substances from the matrix as a first step, which can be challenging, and the subsequent analysis of the extracted additives by gas chromatography (GC), GC–mass spectrometry (MS), high performance liquid chromatography (HPLC), HPLC–MS, capillary electrophoresis, thin-layer chromatography, and other analytical techniques. In the present work, nitrile rubber materials were studied using direct analytical flash pyrolysis hyphenated to GC and electrospray ionization MS in both scan and selected ion monitoring modes to demonstrate that this technique is a good tool to identify the organic additives in nitrile rubber.
In this paper, various enhanced sales forecast methodologies and models for the automobile market are presented. The methods used deliver highly accurate predictions while maintaining the ability to explain the underlying model at the same time. The representation of the economic training data is discussed, as well as its effects on the newly registered automobiles to be predicted. The methodology mainly consists of time series analysis and classical Data Mining algorithms, whereas the data is composed of absolute and/or relative market-specific exogenous parameters on a yearly, quarterly, or monthly base. It can be concluded that the monthly forecasts were especially improved by this enhanced methodology using absolute, normalized exogenous parameters. Decision Trees are considered as the most suitable method in this case, being both accurate and explicable. The German and the US-American automobile market are presented for the evaluation of the forecast models.