Nitric Oxide Mediates Stretch-Induced Ca2+ Release via Activation of Phosphatidylinositol 3-Kinase-Akt Pathway in Smooth Muscle

Hollow smooth muscle organs such as the bladder undergo significant changes in wall tension associated with filling and distension, with attendant changes in muscle tone. Our previous study indicated that stretch induces Ca(2+) release occurs in the form of Ca(2+) sparks and Ca(2+) waves in urinary bladder myocytes. While, the mechanism underlying stretch-induced Ca2+ release in smooth muscle is unknown.We examined the transduction mechanism linking cell stretch to Ca(2+) release. The probability and frequency of Ca(2+) sparks induced by stretch were closely related to the extent of cell extension and the time that the stretch was maintained. Experiments in tissues and single myocytes indicated that mechanical stretch significantly increases the production of nitric oxide (NO) and the amplitude and duration of muscle contraction. Stretch-induced Ca(2+) sparks and contractility increases were abrogated by the NO inhibitor L-NAME and were also absent in eNOS knockout mice. Furthermore, exposure of eNOS null mice to exogenously generated NO induced Ca(2+) sparks. The soluble guanylyl cyclase inhibitor ODQ did not inhibit SICR, but this process was effectively blocked by the PI3 kinase inhibitors LY494002 and wortmannin; the phosphorylation of Akt and eNOS were up-regulated by 204+/-28.6% and 258+/-36.8% by stretch, respectively. Moreover, stretch significantly increased the eNOS protein expression level.Taking together, these results suggest that stretch-induced Ca2+ release is NO dependent, resulting from the activation of PI3K/Akt pathway in smooth muscle

A Cross-Species Analysis of MicroRNAs in the Developing Avian Face

Higher vertebrates use similar genetic tools to derive very different facial features. This diversity is believed to occur through temporal, spatial and species-specific changes in gene expression within cranial neural crest (NC) cells. These contribute to the facial skeleton and contain species-specific information that drives morphological variation. A few signaling molecules and transcription factors are known to play important roles in these processes, but little is known regarding the role of micro-RNAs (miRNAs). We have identified and compared all miRNAs expressed in cranial NC cells from three avian species (chicken, duck, and quail) before and after species-specific facial distinctions occur. We identified 170 differentially expressed miRNAs. These include thirty-five novel chicken orthologs of previously described miRNAs, and six avian-specific miRNAs. Five of these avian-specific miRNAs are conserved over 120 million years of avian evolution, from ratites to galliforms, and their predicted target mRNAs include many components of Wnt signaling. Previous work indicates that mRNA gene expression in NC cells is relatively static during stages when the beak acquires species-specific morphologies. However, miRNA expression is remarkably dynamic within this timeframe, suggesting that the timing of specific developmental transitions is altered in birds with different beak shapes. We evaluated one miRNA:mRNA target pair and found that the cell cycle regulator p27KIP1 is a likely target of miR-222 in frontonasal NC cells, and that the timing of this interaction correlates with the onset of phenotypic variation. Our comparative genomic approach is the first comprehensive analysis of miRNAs in the developing facial primordial, and in species-specific facial development

Tecnologies lingüístiques per a llengües minoritzades el cas de l'alguerès

La tecnologia pot jugar un rol decisiu en els processos de normalització lingüística. La creació de recursos lingüístics -amb el potencial formatiu o de disseminació que comporten, especialment en llengües en procés d'estandardització- és una possibilitat que cal tenir present en dissenyar estratègies per a la normalització. Aquest article se proposa contribuir al procés de normalització de l'alguerès, varietat parlada a l'Alguer (Sardenya) per unes dotze mil persones, mitjançant una anàlisi de les obres de consulta digitals i dels recursos lingüístics existents. En la primera part se proporcionen dades sobre el context sociolingüístic i se fa un estat de la qüestió sobre el procés d'estandardització de l'alguerès. La segona part mira d'identificar, amb referències a altres comunitats lingüístiques en situacions similars, accions en l'àmbit tecnològic que podrien dur-se a terme en paral·lel al procés d'estandardització de l'alguerès.Technology can play a decisive role in linguistic normalisation processes. The creation of linguistic resources (with the potential they have for education or to encourage the spread of languages, especially those in the process of standardisation) is a possibility that should be taken into account in designing normalisation strategies. This article proposes contributing to the process of normalising Algherese, a variety spoken in Alghero (Sardinia) by around twelve thousand people, through an analysis of digital reference works and existing linguistic resources. The first part provides data about the sociolinguistic context and establishes the current situation regarding the process of standardising Algherese. The second part seeks to identify, with references to other language communities in similar situations, actions in the technological sphere that could be carried out in parallel with the process of standardising Algheres

Neuartiges Modell zur Untersuchung der Insulintherapie auf die Ausbildung Biofilm-assoziierter Wunden in diabetischen Mäusen

Objective: Diabetic patients suffer more frequently from biofilm-associated infections than normoglycemic patients. Well described in the literature is a relationship between elevated blood glucose levels in patients and the occurrence of biofilm-associated wound infections. Nevertheless, the underlying pathophysiological pathways leading to this increased infection vulnerability and its effects on biofilm development still need to be elucidated. We developed in our laboratory a model to allow the investigation of a biofilm-associated wound infection in diabetic mice under controlled insulin treatment. Methods: A dorsal skinfold chamber was used on 16 weeks old BKS.Cg-Dock7m +/+ Leprdb/J mice and a wound within the observation field of the dorsal skinfold chamber was created. These wounds were infected with Staphylococcus aureus ATCC 49230 (106 cells/mL). Simultaneously, we implanted implants for sustained insulin release into the ventral subcutaneous tissue (N=5 mice). Mice of the control group (N=5) were treated with sham implants. Serum glucose levels were registered before intervention and daily after the operation. Densitometrical analysis of the wound size was performed at day 0, 3, and 6 after intervention. Mice were sacrificed on day 6 and wound tissue was submitted to fluorescence in situ hybridization (FISH) and colony forming unit (CFU) analysis in addition to immunohistochemical staining to observe wound healing. Experiments were carried out in accordance with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals (protocol number 05/19).Results: The insulin implants were able to reduce blood glucose levels in the mice. Hence, the diabetic mice in the intervention group were normoglycemic after the implantation. The combination with the dorsal skinfold chamber allowed for continuous, in vivo measurements of the infection development. Implantation of the insulin implant and the dorsal skinfold chamber was a tolerable condition for the diabetic mice. We succeeded to realize reproducible biofilm infections in the animals. Discussion: We developed a novel model to assess interactions between blood glucose level and S. aureus -induced biofilm-associated wound infections. The combination of the dorsal skinfold chamber model with a sustained insulin treatment has not been described so far. It allows a broad field of glucose and insulin dependent studies of infection.Einleitung: Patienten mit Diabetes mellitus leiden häufiger unter Biofilm-assoziierten Infekten als normoglykämische Patienten. Das vermehrte zeitgleiche Auftreten erhöhter Blutzuckerwerte und Biofilm-assoziierter Wundinfekte ist gut beschrieben; der dieser erhöhten Infektvulnerabilität zugrundeliegende Pathomechanismus ist allerdings bisher nicht abschließend erforscht. Um dieses Forschungsfeld künftig tiefergehend zu studieren, haben wir in unserem Labor ein neues Tiermodel zur Untersuchung der Biofilmbildung in diabetischen Mäusen unter einer kontrollierten Insulinbehandlung etabliert. Material und Methoden: 16 Wochen alten BKS.Cg-Dock7m +/+ Leprdb/J Mäusen wurde in einem Rückenhautkammermodell eine dermale Wunde gesetzt. Diese Wunden wurden mit Staphylococcus aureus ATCC 49230 (106 Zellen/mL) infiziert. Zeitgleich wurden den Tieren je nach Versuchsgruppe (je N=5) entweder Insulin verabreichende subkutane Implantate (LinShin Canada Inc., Toronto, Canada) oder wirkstofffreie Implantate appliziert. Die Tiere lebten insgesamt 6 Tage. Täglich wurden das Gewicht, die Temperatur und Blutzuckerwerte der Tiere bestimmt. Nach 6 Tagen wurden Gewebeproben jeweils für Fluoreszenz-in-situ -Hybridisierung, CFU und immunhistochemische Färbungen gewonnen. Die Versuche sind entsprechend der Tierversuchsordnung des Landes Sachsen durchgeführt worden (TVV05/19).Ergebnisse: Wir konnten ein neuartiges zuverlässiges Modell zur Untersuchung der Insulintherapie auf die Ausbildung Biofilm-assoziierter Wunden in diabetischen Mäusen etablieren. Die Insulinpumpentherapie konnte eine Reduktion der Blutzuckerwerte erreichen. Die Kombination des Rückenhautkammermodells, welches kontinuierliche In-vivo-Untersuchungen der Infektion erlaubt, mit Insulinimplantaten ist ein für die diabetischen Mäuse gut tolerierbares Modell.Diskussion: Wir haben ein neuartiges Modell zur Untersuchung des Zusammenhangs zwischen Insulin- und Blutzuckerwerten auf die Bildung von Biofilm-assoziierten Wundinfekten am diabetischen Tiermodell entwickelt. Dieses Modell eröffnet ein weites Spektrum an künftigen Forschungsfeldern

Flight 4.0: The Changing Technology Landscape of Aeronautics

This chapter draws the readers into a comprehensive discussion about the advances in Information and Communication Technologies (ICT) and their influence on the technology landscape of aeronautics. It gives a rough overview of the advances in technical systems from the industrial revolution up until Industry 4.0 and elaborates the reflection of these advancements in aeronautics from the pioneers era toward Flight 4.0. It briefly describes various recent fields of research in ICT such as Cyber-Physical Systems (CPS), Internet of Things (IoT), wireless networks, multicore architectures, Service-Oriented Architecture (SOA), cloud computing, big data, and modern software engineering methodologies as the parts of future aeronautical engineering body of knowledge. Thereafter, it describes aeronautical informatics as an establishing interdisciplinary field of study of applied informatics and aeronautics

Formation of mega-scale glacial lineations observed beneath a West Antarctic ice stream

Most discharge from large ice sheets takes place through fast-flowing ice streams and their speed is strongly modulated by interactions between the ice and the underlying sediments. Seismic surveys and investigations through boreholes have revealed a spatial association between fast ice flow and saturated deformable sediments. Nevertheless, our knowledge of the morphology of the interface between ice and sediments is still limited, resulting in only rudimentary understanding of the basal boundary conditions beneath ice streams and the generation of subglacial bedforms. Here we present radar data from the bed of a West Antarctic ice stream that reveal the presence of mega-scale glacial lineations. We combine these data with previously published seismic data and show that these lineations develop in areas of dilatant deforming till and are part of a dynamic sedimentary system that undergoes significant change by erosion and deposition on decadal timescales. We find that the mega-scale glacial lineations are indistinguishable from those found on beds of palaeo-ice streams, providing conclusive evidence for the hypothesis that highly elongate bedforms are a characteristic of fast-flow regions in ice sheets