Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes

AbstractHuman B lymphocytes express an ATP-gated ion channel (P2Z receptor), which shares similarities with the recently identified P2X7 receptor. Using gene specific primers, we have now isolated P2X7 cDNA from the total RNA of human B lymphocytes. This hP2X7 receptor subtype was expressed in Xenopus oocytes and electrophysiologically characterized. The hP2X7 receptor is similar to, but does not completely match, P2Z of human B cells. The hP2X7 receptors resemble the P2Z receptors with regard to the ATP concentration of half maximal activation, reproducibility, permeation characteristics and lack of desensitization of the ATP-evoked currents. However, in contrast to the native lymphocytic P2Z receptor, the time course of activation of hP2X7 displayed an additional linearly increasing current component. Furthermore, a second, small and slowly deactivating current component exists only in hP2X7 expressed in oocytes. The activation and deactivation kinetics as well as permeation characteristics of hP2X7 are different from rat P2X7 recently expressed in oocytes. Unlike in mammalian cells, hP2X7 expressed in Xenopus oocytes is not sufficient to induce large non-selective pores

Praxisleitende Momente in Wiener Pflegeheimen

Die vorliegende Diplomarbeit entstand im Zuge des Forschungsprojekts „Lebensqualität im Pflegeheim“, das von der Universität Wien finanziert und in Kooperation der Institute für Soziologie, Pflegewissenschaften und Bildungswissenschaften – im Speziellen von der Forschungseinheit „Psychoanalytische Pädagogik“ - durchgeführt wurde. In dieser Arbeit werden leitfadengestütze Interviews, welche mit 16 Pflegepersonen aus zwei Wiener Pflegeheimen geführt wurden, aus einem psychoanalytisch pädagogischen Blickwinkel betrachtet. Im Mittelpunkt unseres Interesses standen einerseits jene Momente, die für das Handeln der einzelnen interviewten Personen in der konkreten Pflegesituation ausschlaggebend waren, und andererseits die Frage, in welcher Art und Weise die Pflegepersonen eine kurz vor dem Interview stattgefundene, konkrete Pflegehandlung beschreiben und begründen. Die Interpretationen der Interviews basieren auf einem Kategoriensystem, das im Rahmen des Forschungsprojektes in Zusammenarbeit von Lehrbeauftragten und Studierenden entwickelt wurde. Die Inhalte der einzelnen Kategorien wurden vor dem Hintergrund psychoanalytisch orientierter Theorien interpretiert. Hier galt es das Augenmerk nicht nur auf jene praxisleitenden Momente zu richten, die in den Interviews sprachlich zum Ausdruck gebracht wurden, sondern auch auf jene Momente des Wahrnehmens, emotionalen Erlebens und Denkens, denen latent praxisleitende Bedeutung zukommt, aber von den Pflegepersonen nicht sprachlich zum Ausdruck gebracht wurden. Die Auswertung der Interviews ergibt, dass sich die Pflegepersonen sowohl in der Beschreibung der Pflegehandlung als auch in der Auskunft über die Beweggründe ihres Handelns vorwiegend auf körperliche Besonderheiten der HeimbewohnerInnen beziehen und belastende emotionale Aspekte der pflegerischen Tätigkeit nicht zur Sprache gebracht werden, sehr wohl aber praxisleitende Bedeutung haben dürften. Die Ergebnisse der Untersuchung dienen als Grundlage für die Beantwortung der zweiten Forschungsfrage, in der Überlegungen zur Aus- und Weiterbildung von Pflegepersonen angestellt werden

Nutritional Value of the Duckweed Species of the Genus Wolffia (Lemnaceae) as Human Food

Species of the genus Wolffia are traditionally used as human food in some of the Asian countries. Therefore, all 11 species of this genus, identified by molecular barcoding, were investigated for ingredients relevant to human nutrition. The total protein content varied between 20 and 30% of the freeze-dry weight, the starch content between 10 and 20%, the fat content between 1 and 5%, and the fiber content was ~25%. The essential amino acid content was higher or close to the requirements of preschool-aged children according to standards of the World Health Organization. The fat content was low, but the fraction of polyunsaturated fatty acids was above 60% of total fat and the content of n-3 polyunsaturated fatty acids was higher than that of n-6 polyunsaturated fatty acids in most species. The content of macro- and microelements (minerals) not only depended on the cultivation conditions but also on the genetic background of the species. This holds true also for the content of tocopherols, several carotenoids and phytosterols in different species and even intraspecific, clonal differences were detected in Wolffia globosa and Wolffia arrhiza. Thus, the selection of suitable clones for further applications is important. Due to the very fast growth and the highest yield in most of the nutrients, Wolffia microscopica has a high potential for practical applications in human nutrition

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy

Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications

Bridging the research-implementation gap in IUCN Red List assessments

The International Union for Conservation of Nature (IUCN) Red List of Threatened Species is central in biodiversity conservation, but insufficient resources hamper its long-term growth, updating, and consistency. Models or automated calculations can alleviate those challenges by providing standardised estimates required for assessments, or prioritising species for (re-)assessments. However, while numerous scientific papers have proposed such methods, few have been integrated into assessment practice, highlighting a critical research-implementation gap. We believe this gap can be bridged by fostering communication and collaboration between academic researchers and Red List practitioners, and by developing and maintaining user-friendly platforms to automate application of the methods. We propose that developing methods better encompassing Red List criteria, systems, and drivers is the next priority to support the Red List.Peer reviewe

8-MW wind turbine tower computational shell buckling benchmark. Part 1:an international ‘round-robin’ exercise

An assessment of the elastic-plastic buckling limit state for multi-strake wind turbine support towers poses a particular challenge for the modern finite element analyst, who must competently navigate numerous modelling choices related to the tug-of-war between meshing and computational cost, the use of solvers that are robust to highly nonlinear behaviour, the potential for multiple near-simultaneously critical failure locations, the complex issue of imperfection sensitivity and finally the interpretation of the data into a safe and economic design.This paper reports on an international ‘round-robin’ exercise conducted in 2022 aiming to take stock of the computational shell buckling expertise around the world which attracted 29 submissions. Participants were asked to perform analyses of increasing complexity on a standardised benchmark of an 8-MW multi-strake steel wind turbine support tower segment, from a linear elastic stress analysis to a linear bifurcation analysis to a geometrically and materially nonlinear buckling analysis with imperfections. The results are a showcase of the significant shell buckling expertise now available in both industry and academia.This paper is the first of a pair. The second paper presents a detailed reference solution to the benchmark, including an illustration of the Eurocode-compliant calibration of two important imperfection forms

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention