Aldosterone signaling and soluble adenylyl cyclase—A nexus for the kidney and vascular endothelium

AbstractThe steroid hormone aldosterone regulates the reabsorption of water and ions in the kidney and plays a central role in blood pressure regulation and homeostasis. In recent years, the vascular endothelium has been established as an important aldosterone target organ with major implications in renal and cardiovascular health and disease. Different lines of evidence suggest that the calcium- and bicarbonate-activated soluble adenylyl cyclase (sAC) is a novel mediator of aldosterone signaling in both the kidney and vascular endothelium. This review summarizes our current understanding of the molecular mechanisms of sAC gene expression regulation in the kidney and vascular endothelium and outlines the potential clinical implications of sAC in chronic kidney disease and cardiovascular disease. This review is part of a special issue entitled: The role of soluble adenylyl cyclase in health and disease. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease

Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P—results from a phase I study

Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevan

The Yo-Yo Intermittent Tests: A Systematic Review and Structured Compendium of Test Results

Background: Although Yo-Yo intermittent tests are frequently used in a variety of sports and research studies to determine physical fitness, no structured reference exists for comparison and rating of test results. This systematic review of the most common Yo-Yo tests aimed to provide reference values for test results by statistical aggregation of published data.Methods: A systematic literature search for articles published until August 2017 was performed in MEDLINE, Web of Science, SPORTDiscus and Google Scholar. Original reports on healthy females and males ≥16 years were eligible for the analysis. Sub-maximal test versions and the Yo-Yo Intermittent Recovery Level 1 Children's test (YYIR1C) were not included.Results: 248 studies with 9,440 participants were included in the structured analysis. The Yo-Yo test types most frequently used were the Yo-Yo Intermittent Recovery Level 1 (YYIR1, 57.7%), the Yo-Yo Intermittent Recovery Level 2 (YYIR2, 28.0%), the Yo-Yo Intermittent Endurance Level 2 (YYIE2, 11.4%), and the Yo-Yo Intermittent Endurance Level 1 (YYIE1, 2.9%) test. For each separate test, reference values (global means and percentiles) for sports at different levels and both genders were calculated.Conclusions: Our analysis provides evidence that Yo-Yo intermittent tests reference values differ with respect to the type and level of sport performed.The presented results may be used by practitioners, trainers and athletes to rate Yo-Yo intermittent test performance levels and monitor training effects

Psychiatric In-Patients Are More Likely to Meet Recommended Levels of Health-Enhancing Physical Activity If They Engage in Exercise and Sport Therapy Programs

Background:; People with mental disorders engage in sedentary behaviors more often than their healthy counterparts. In Switzerland, nearly all psychiatric hospitals offer structured exercise and sport therapy as part of their standard therapeutic treatment. However, little is known about the degree to which psychiatric patients make use of these treatment offers. The aim of this study is to examine, in a sample of psychiatric in-patients (a) how many participate in the structured exercise and sport therapy programs offered by the clinic, (b) how many engage in exercise and sport activities on an individual basis, and (c) how many meet recommended levels of health-enhancing physical activity during their stay at the clinic. Furthermore, we examine whether those who engage in exercise and sport activities are more likely to meet internationally accepted physical activity recommendations.; Methods:; 107 psychiatric in-patients (49% women, M; age; = 39.9 years) were recruited at three psychiatric clinics in the German-speaking part of Switzerland. All participants were engaged in treatment and received usual care. Based on accelerometer data, participants were classified as either meeting or not meeting physical activity recommendations (≥150 min of moderate-to-vigorous physical activity per week). Participation in structured and individually performed exercise and sport activities was assessed with the Simple Physical Activity Questionnaire.; Results:; In total, 57% of all patients met physical activity recommendations. 55% participated in structured exercise and sport therapy activities, whereas only 22% of all patients engaged in exercise and sport activities independently. Psychiatric patients were significantly more likely to meet recommended levels of health-enhancing physical activity if they engaged in at least 60 min per week of structured exercise and sport therapy or in at least 30 min of individually performed exercise and sport activity.; Conclusions:; Given that prolonged immobilization and sedentary behavior have harmful effects on patients' physical and mental well-being, promoting exercise and sport activities is an important endeavor in psychiatric care. Clinics currently succeed in involving between 50 and 60% of all patients in sufficient physical activity. While this is encouraging, more systematic efforts are needed to ensure that all patients get enough physical activity

Realizing efficient topological temporal pumping in electrical circuits

Quantized adiabatic transport can occur when a system is slowly modulated over time. In most realizations however, the efficiency of such transport is reduced by unwanted dissipation, back-scattering, and non-adiabatic effects. In this work, we realize a topological adiabatic pump in an electrical circuit network that supports remarkably stable and long-lasting pumping of a voltage signal. We further characterize the topology of our system by deducing the Chern number from the measured edge band structure. To achieve this, the experimental setup makes use of active circuit elements that act as time-variable voltage-controlled inductors.Comment: main (5 pages, 3 figures) plus supplement (8 pages, 4 figures

Simulating hyperbolic space on a circuit board

The Laplace operator encodes the behavior of physical systems at vastly different scales, describing heat flow, fluids, as well as electric, gravitational, and quantum fields. A key input for the Laplace equation is the curvature of space. Here we discuss and experimentally demonstrate that the spectral ordering of Laplacian eigenstates for hyperbolic (negatively curved) and flat two-dimensional spaces has a universally different structure. We use a lattice regularization of hyperbolic space in an electric-circuit network to measure the eigenstates of a ‘hyperbolic drum’, and in a time-resolved experiment we verify signal propagation along the curved geodesics. Our experiments showcase both a versatile platform to emulate hyperbolic lattices in tabletop experiments, and a set of methods to verify the effective hyperbolic metric in this and other platforms. The presented techniques can be utilized to explore novel aspects of both classical and quantum dynamics in negatively curved spaces, and to realise the emerging models of topological hyperbolic matter

The LRU Rover for Autonomous Planetary Exploration and its Success in the SpaceBotCamp Challenge

The task of planetary exploration poses many challenges for a robot system, from weight and size constraints to sensors and actuators suitable for extraterrestrial environment conditions. As there is a significant communication delay to other planets, the efficient operation of a robot system requires a high level of autonomy. In this work, we present the Light Weight Rover Unit (LRU), a small and agile rover prototype that we designed for the challenges of planetary exploration. Its locomotion system with individually steered wheels allows for high maneuverability in rough terrain and the application of stereo cameras as its main sensor ensures the applicability to space missions. We implemented software components for self-localization in GPS-denied environments, environment mapping, object search and localization and for the autonomous pickup and assembly of objects with its arm. Additional high-level mission control components facilitate both autonomous behavior and remote monitoring of the system state over a delayed communication link. We successfully demonstrated the autonomous capabilities of our LRU at the SpaceBotCamp challenge, a national robotics contest with focus on autonomous planetary exploration. A robot had to autonomously explore a moon-like rough-terrain environment, locate and collect two objects and assemble them after transport to a third object - which the LRU did on its first try, in half of the time and fully autonomous

Temporally-Controlled Site-Specific Recombination in Zebrafish

Conventional use of the site-specific recombinase Cre is a powerful technology in mouse, but almost absent in other vertebrate model organisms. In zebrafish, Cre-mediated recombination efficiency was previously very low. Here we show that using transposon-mediated transgenesis, Cre is in fact highly efficient in this organism. Furthermore, temporal control of recombination can be achieved by using the ligand-inducible CreERT2. Site-specific recombination only occurs upon administration of the drug tamoxifen (TAM) or its active metabolite, 4-hydroxy-tamoxifen (4-OHT). Cre-mediated recombination is detectable already 4 or 2 hours after administration of TAM or 4-OHT, demonstrating fast recombination kinetics. In addition, low doses of TAM allow mosaic labeling of single cells. Combined, our results show that conditional Cre/lox will be a valuable tool for both, embryonic and adult zebrafish studies. Furthermore, single copy insertion transgenesis of Cre/lox constructs suggest a strategy suitable also for other organisms