Conditional deletion of LRRC8A in the brain reduces stroke damage independently of swelling-activated glutamate release

The ubiquitous volume-regulated anion channels (VRACs) facilitate cell volume control and contribute to many other physiological processes. Treatment with non-specific VRAC blockers or brain-specific deletion of the essential VRAC subunit LRRC8A is highly protective in rodent models of stroke. Here, we tested the widely accepted idea that the harmful effects of VRACs are mediated by release of the excitatory neurotransmitter glutamate. We produced conditional LRRC8A knockout either exclusively in astrocytes or in the majority of brain cells. Genetically modified mice were subjected to an experimental stroke (middle cerebral artery occlusion). The astrocytic LRRC8A knockout yielded no protection. Conversely, the brain-wide LRRC8A deletion strongly reduced cerebral infarction in both heterozygous (Het) and full KO mice. Yet, despite identical protection, Het mice had full swelling-activated glutamate release, whereas KO animals showed its virtual absence. These findings suggest that LRRC8A contributes to ischemic brain injury via a mechanism other than VRAC-mediated glutamate release

Begriff und Zweck "sozialstaatlicher" Leistungen für Kinder in Österreich

Sozialstaaten und die damit einhergehenden Leistungen, sind durch gesellschaftliche Veränderungen einem stetigen Wandel unterzogen. Der Staat Österreich hat den Sozialstaat nicht explizit in seiner Verfassung verankert, trotzdem kennt er, losgelöst von der verfassungsrechtlichen Gewährleistung, unterschiedlichste Möglichkeiten um Kinder in seinen Normen zu berücksichtigen und Familien zu entlasten. Er kann durch gezielte Regelungen im Bereich des Arbeitsrechts, sowie im Sozial- und Steuerrecht wirtschaftlich benachteiligte Gruppen fördern. Kinder und Familien fließen demnach in viele verschiedene Rechtsbereiche ein, in denen Versucht wird diese Gruppe zu schützen oder zu unterstützen. Die arbeitsrechtlichen Aspekte finden sich in den Bestimmungen über den ArbeitnehmerInnenschutz, sowie in bestimmten Freistellungs- und Arbeitszeitregelungen. Sozialrechtliche Maßnahmen reichen von Leistungen der Sozialversicherungen, über die des Familienlastenausgleichsfonds, bis hin zu jenen der einzelnen Bundesländer. Spezielle Regelungen im Steuerrecht, vorrangig im Einkommensteuerrecht, können auch zu einem Ausgleich der Familienlasten führen, indem spezielle Steuererleichterungen vorgesehen werden. All diese Leistungen werden aufgearbeitet, um die Frage beantworten zu können, welcher Sinn und Zweck mit ihnen verfolgt wird und welche Konsequenzen sich aus den unterschiedlichen Anspruchsvoraussetzungen ergeben können. Der Anspruch auf sozialstaatliche Leistungen wird in dieser Arbeit zudem auch aus unionsrechtlicher Sicht behandelt. Im Zuge dessen wird auch auf aktuelle Probleme der Indexierung bestimmter Leistungen für Unionsbürger_Innen eingegangen.Welfare states and the services they provide are subject to constant change as a result of social changes. The Austrian state has not explicitly anchored the welfare state in its constitution, but nevertheless, detached from the constitutional guarantee, it knows various possibilities to include children in its norms and to relieve families. It can promote economically disadvantaged groups through targeted regulations in the area of labour law as well as in social and tax law. Accordingly, children and families are included in many different areas of law in which attempts are made to protect or support this group. The labour law aspects can be found in the provisions on the protection of employees, as well as in certain exemption and working time regulations. Social law measures range from social insurance benefits to those of the Family Burden Equalisation Fund and those of the individual federal states. Special regulations in tax law, primarily in income tax law, can also lead to a balancing of family burdens by providing special tax relief. All of these benefits will be reviewed in order to be able to answer the question as to what sense and purpose they serve and what consequences may result from the different eligibility criteria. The entitlement to welfare state benefits is also dealt with from the perspective of EU law in this paper. In the course of this, current problems of indexation of certain benefits for EU citizens are also addressed.Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Diplomarbeit, 2020(VLID)486856

Evaluierung der Science Week @ Austria 2002

Die Science Week schreibt sich in eine Reihe von Aktivitäten ein, die über die letzten Jahre versucht haben, die österreichische Landschaft im Bereich der Wissenschaftskommunikation zu beleben. Unter dem Titel „Science Week @ Austria – Eine Vergnügungsreise durch die Wissenschaft“ wird seit dem Jahr 2000 jährlich eine etwa 10-tägige Veranstaltung organisiert, in der WissenschaftlerInnen aufgerufen sind, ihre eigene Arbeit einer breiteren Öffentlichkeit gegenüber darzustellen. Bei dem vorliegenden Projekt geht es um eine Evaluierung der Science Week mit dem Ziel, damit auch einen Beitrag für eine entsprechende Weiterentwickelung zu leisten. Es geht darum, ein den realen Gegebenheiten und Möglichkeiten angepasstes Event zu gestalten und dabei die unterschiedlichen Akteure zu Wort kommen zu lassen. Deshalb wurde als Evaluierungsmethode auch eine „symmetrische Evaluierung“ gewählt. Das Ziel ist also nicht, nach einem starren Kriterienkatalog eine Bewertung vorzunehmen, sondern die verschiedenen Positionen, Sichtweisen und Erwartungen der unterschiedlichen Akteure zu analysieren, zusammenzuführen und so zu einer ganzheitlichen Betrachtungsweise der Science Week zu gelangen

Capacity of the medullary cavity of tibia and femur for intra-bone marrow transplantation in mice.

Intra-bone marrow transplantation (IBMT) has been adapted for mouse models to improve the seeding efficiency of transplanted hematopoietic stem and progenitor cells. Commonly used injection volumes for IBMT into the tibia differ between 10 and 40 μL even though considerable amounts of injected cells leak into the blood circulation immediately after injection. Injection of 3 μL trypan blue into the tibia of dead BALB/c mice showed staining in large vessels of hind limbs, even without supporting circulation. We therefore tested the effective capacity of the medullary cavity of dissected tibiae and femora of different mouse strains by bioluminescence imaging after injection of luciferase expressing cells. Cell leakage was already observed at 3 μL of injection volume and the measured emission rate increased significantly when 5 and 10 μL of volume with the same cell concentration were injected. Surprisingly, increasing injection volumes containing constant cell amounts resulted in comparable emission rates, suggesting a similar amount of leaked and absorbed cells independent of the injection volume. However, the absorption of a specific amount of injected cells could not be confirmed, as the ratio of leaked to absorbed cells was similar between IBMT that were performed with a constant injection volume containing either low or high cell amounts. In summary, for optimal cell transplantation via IBMT in mice we suggest to inject a high concentrated cell suspension with a maximum injection volume of 3 μL

Microparticle-based Controlled Drug Delivery Systems: From Experiments to Statistical Analysis and Design

Controlled drug delivery (CDD), the controlled release and delivery of therapeutic drugs inside the human body, is a promising approach to increase the efficacy of drug administration and reduce harmful side effects to the body. CDD has been a major research focus in the field of molecular communications (MC) with the goal to aid the design and optimization of CDD systems with communication theoretical analysis. However, the existing studies of CDD under the MC framework are purely theoretical, and the potential of MC for the development of practical CDD applications remains yet to be shown. This paper presents a step towards filling this research gap. Specifically, we present a novel MC-based model for a specific CDD system in which drugs are embedded into microparticles and released gradually towards the target site. It is demonstrated that the proposed model is able to faithfully reproduce experimental data. Furthermore, statistical analysis is conducted to explore the impact of the microparticle size on the drug release. The presented results reveal the sensitivity of the drug release to changes in the microparticle size. In this way, the proposed model can be used for the design of future microparticle-based CDD systems.Comment: 9 pages, 3 figures, 2 tables. This paper has been submitted in part to the 2023 IEEE Global Communications Conference (Globecom

Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness.

Cancer stem cells have been described in various cancers including squamous tumours of the skin by their ability to reform secondary tumours upon transplantation into immunodeficient mice. Here, we used transplantation of limiting dilution of different populations of FACS-isolated tumour cells from four distinct mouse models of squamous skin tumours to investigate the frequency of tumour propagating cells (TPCs) at different stages of tumour progression. We found that benign papillomas, despite growing rapidly in vivo and being clonogenic in vitro, reformed secondary tumours upon transplantation at very low frequency and only when tumour cells were co-transplanted together with tumour-associated fibroblasts or endothelial cells. In two models of skin squamous cell carcinoma (SCC), TPCs increased with tumour invasiveness. Interestingly, the frequency of TPCs increased in CD34(HI) but not in CD34(LO) SCC cells with serial transplantations, while the two populations initially gave rise to secondary tumours with the same frequency. Our results illustrate the progressive increase of squamous skin TPCs with tumour progression and invasiveness and reveal that serial transplantation may be required to define the long-term renewal potential of TPCs.Journal ArticleFLWINSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice

Cyclooxygenases are known as important regulators of metabolism and immune processes via conversion of C20 fatty acids into various regulatory lipid mediators, and cyclooxygenase activity has been implicated in browning of white adipose tissues. We generated transgenic (TG) C57BL/6 mice expressing the Ptgs2 gene encoding cyclooxygenase-2 (COX-2) in mature adipocytes. TG mice fed a high-fat diet displayed marginally lower weight gain with less hepatic steatosis and a slight improvement in insulin sensitivity, but no difference in glucose tolerance. Compared to littermate wildtype mice, TG mice selectively reduced inguinal white adipose tissue (iWAT) mass and fat cell size, whereas the epididymal (eWAT) fat depot remained unchanged. The changes in iWAT were accompanied by increased levels of specific COX-derived lipid mediators and increased mRNA levels of interleukin-33, interleukin-4 and arginase-1, but not increased expression of uncoupling protein 1 or increased energy expenditure. Epididymal WAT (eWAT) in TG mice exhibited few changes except from increased infiltration with eosinophils. Our findings suggest a role for COX-2-derived lipid mediators from adipocytes in mediating type 2 immunity cues in subcutaneous WAT associated with decreased hepatic steatosis, but with no accompanying induction of browning and increased energy expenditure

Within-range translocations and their consequences in European larch

In contrast to biological invasions, translocations of individuals within a species range are understudied, due to difficulties in systematically detecting them. This results in limited knowledge about the corresponding processes and uncertainties regarding the status of extant populations. European larch, a forest tree whose fragmented native distribution is restricted to the Alps and to other Central European mountains, has been massively planted for at least 300 years. Here we focus on the genetic characterization of translocations having taken place within its native range. Microsatellite variation at 13 nuclear loci and sequence data of two mitochondrial DNA fragments were analyzed on the basis of a comprehensive range-wide population sample. Two complementary methods (Geneclass and Structure) were used to infer translocation events based on nuclear data whereas mitochondrial data were used for validation of these inferences. Using Geneclass, we found translocation events in a majority of populations. Additional cases of translocation and many instances of admixture were identified using Structure, thanks to the clear-cut ancestral genetic structure detected in this species. In particular, a strong divide between Alpine and Central European populations, also apparent at mitochondrial markers, helped uncover details on translocation events and related processes. Translocations and associated admixture events were found to be heterogeneously distributed across the species range, with a particularly high frequency in Central Europe. Furthermore, translocations frequently involved multiple geographic sources, some of which were over-represented. Our study illustrates the importance of range-wide investigations for tracing translocations back to their origins and for revealing some of their consequences. It provides some first clues for developing suitable conservation and management strategies