The circumventricular organs participate in the immunopathogenesis of experimental autoimmune encephalomyelitis

BACKGROUND: During inflammatory conditions of the central nervous system (CNS), such as in multiple sclerosis or in its animal model, experimental autoimmune encephalomyelitis (EAE), immune cells migrate from the blood stream into the CNS parenchyma and into the cerebrospinal fluid (CSF) spaces. The endothelial blood-brain barrier (BBB) has been considered the most obvious entry site for circulating immune cells. Recently, the choroid plexus has been considered as an alternative entry site for circulating lymphocytes into the CSF. The choroid plexus, belongs to the circumventricular organs (CVOs) localized in the walls of the ventricles. Other CVOs, which similar to the choroid plexus lack an endothelial BBB, have not been considered as possible entry sites for immune cells into the CNS parenchyma or the CSF. Here we asked, whether CVOs are involved in the recruitment of inflammatory cells into the brain during EAE. METHODS: We performed an extensive immunohistological study on the area postrema (AP), the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT) and the median eminence (ME) in frozen brain sections from healthy SJL mice and mice suffering from EAE. Expression of cell adhesion molecules, the presence of leukocyte subpopulations and the detection of major histocompatibility complex antigen expression was compared. RESULTS: Similar changes were observed for all four CVOs included in this study. During EAE significantly increased numbers of CD45(+ )leukocytes were detected within the four CVOs investigated, the majority of which stained positive for the macrophage markers F4/80 and Mac-1. The adhesion molecules ICAM-1 and VCAM-1 were upregulated on the fenestrated capillaries within the CVOs. A considerable upregulation of MHC class I throughout the CVOs and positive immunostaining for MHC class II on perivascular cells additionally documented the immune activation of the CVOs during EAE. A significant enrichment of inflammatory infiltrates was observed in close vicinity to the CVOs. CONCLUSION: Our data indicate that the CVOs are a site for the entry of immune cells into the CNS and CSF and consequently are involved in the inflammatory process in the CNS during EAE

Exploring the extension of AR-visualization and interaction for large physical spaces

Während sich Augmented Reality (AR) heute oft auf die Interaktion und Überlagerung von klar erreichbaren Objekten konzentriert, stellt die Navigation in riesigen, informationsreichen Umgebungen eine besondere Herausforderung dar, vor allem wenn die virtuellen Objekte weit entfernt sind, sich überlappen oder sich in einer komplexen Umgebung befinden. Die Entwicklung einer Lösung, die die visuelle Unübersichtlichkeit minimiert und gleichzeitig die wichtigsten Informationen vermittelt, ist noch nicht vollständig realisiert. Diese Arbeit untersucht die Anwendung von AR für die Visualisierung von großen Bereichen mit hoher Informationsdichte, wie zum Beispiel Produktionshallen. Sie befasst sich mit den Einschränkungen bestehender AR-Lösungen und schlägt einen Ansatz vor, der einen vordefinierten Blickpunkt als Aussichtspunkt verwendet. Die Implementierung findet in einer Fabrikhalle statt, wobei AR Head-Mounted Displays (HMD) zur interaktiven Datenüberlagerung eingesetzt werden. Zu den Herausforderungen gehören geeignete Tracking-Techniken, die Visualisierung von Daten in großen physikalischen Dimensionen und die Interaktion des Benutzers mit teilweise verdeckten Informationen von verschiedenen entfernten Orten. Eine Nutzerstudie evaluiert die geeigneten Interaktionstechniken und den Gesamtnutzen. Insgesamt zielt diese Forschung darauf ab, die Visualisierung und Interaktion in industriellen und architektonischen Kontexten zu verbessern. Die Ergebnisse zeigen, dass das System für seine Zielanwendung als hilfreich wahrgenommen wird und dass ein 2D-Übersichtsmenü aufgrund seiner Zuverlässigkeit als allgegenwärtige Interaktionsmöglichkeit gewünscht wird. Für ein besseres Nutzererlebnis wird Head Gaze oder Eye-Tracking bevorzugt. Head Gaze ermöglicht eine präzisere Zielführung, während der Eye Gaze zu einem besseren Erlebnis, mehr Immersion und weniger körperlicher Anstrengung führt. Die weit verbreitete Hand Ray Interaktion schnitt am schlechtesten ab, weil die exakte Bewegung schwierig zu lernen war.While present-day Augmented Reality (AR) often focuses on the interaction and superimposition of clearly reachable objects, navigating vast, information-rich environments presents unique challenges, especially when virtual objects are distant, overlapping, or in complex surroundings. Crafting a solution that minimizes visual clutter while conveying essential information has yet to be fully realized. This thesis explores the application of AR for visualizing information-dense large areas like production halls. It addresses the limitations of existing AR solutions and proposes an approach using a predefined viewpoint as a vantage point. The implementation takes place in a factory shop floor, utilizing AR Head-Mounted Displays (HMD) for interactive data superimposition. Challenges include suitable tracking techniques, data visualization in large physical dimensions and user interaction with partly occluded information of various distant locations. A user study evaluates suiting interaction techniques and the overall utility. On the whole, this research aims to enhance visualization and interaction in industrial and architectural contexts. Results show that the system is perceived as helpful for its target application and that an overview 2D menu, due to its reliability is desired as an omnipresent option for interaction. For a better user experience, head gaze or eye tracking is preferred. Head Gaze enables more precise pointing while eye gaze tends to lead to a better experience, immersion and less physical effort. The widespread far hand ray interaction performed worst, because the exact movement was difficult to learn

Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans. Here, we performed an exploratory analysis of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and drug-naïve patients with early MS using multiplexed single-cell mass cytometry and algorithm-based data analysis. Two antibody panels comprising a total of 64 antibodies were designed to comprehensively analyse diverse immune cell populations, with particular emphasis on monocytes. PBMC composition and marker expression were overall similar between the groups. However, an increased abundance of CCR7+ and IL-6+ T cells was detected in early MS-PBMCs, whereas NFAT1hiT-bethiCD4+ T cells were decreased. Similarly, we detected changes in the subset composition of the CCR7+ and MIPβhi HLA-DR+ lymphocyte compartment. Only mild alterations were detected in monocytes/myeloid cells of patients with early MS, namely a decreased abundance of CD141hiIRF8hiCXCR3+CD68- dendritic cells. Unlike in Crohn's disease, no significant differences were found in the monocyte fraction of patients with early MS compared to healthy controls. This study provides a valuable resource for future studies designed to characterise and target diverse PBMC subsets in MS

HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control

Dysregulation of cholesterol homeostasis in human lung cancer tissue and tumour-associated macrophages

Background Based on reports on elevated cholesterol levels in cancer cells, strategies to lower cholesterol synthesis have been suggested as an antitumour strategy. However, cholesterol depletion has also been shown to induce tumour-promoting actions in tumour-associated macrophages (TAMs). Methods We performed lipidomic and transcriptomic analyses of human lung cancer material. To assess whether the TAM phenotype is shaped by secreted factors produced by tumour cells, primary human monocyte-derived macrophages were polarized towards a TAM-like phenotype using tumour cell-conditioned medium. Findings Lipidomic analysis of lung adenocarcinoma (n=29) and adjacent non-tumour tissues (n=22) revealed a significant accumulation of free cholesterol and cholesteryl esters within the tumour tissue. In contrast, cholesterol levels were reduced in TAMs isolated from lung adenocarcinoma tissues when compared with alveolar macrophages (AMs) obtained from adjacent non-tumour tissues. Bulk-RNA-Seq revealed that genes involved in cholesterol biosynthesis and metabolism were downregulated in TAMs, while cholesterol efflux transporters were upregulated. In vitro polarized TAM-like macrophages showed an attenuated lipogenic gene expression signature and exhibited lower cholesterol levels compared with non-polarized macrophages. A genome-wide comparison by bulk RNA-Seq confirmed a high similarity of ex vivo TAMs and in vitro TAM-like macrophages. Modulation of intracellular cholesterol levels by either starving, cholesterol depletion, or efflux transporter inhibition indicated that cholesterol distinctly shapes macrophage gene expression. Interpretation Our data show an opposite dysregulation of cholesterol homeostasis in tumour tissue vs. TAMs. Polarization of in vitro differentiated macrophages by tumour cell-conditioned medium recapitulates key features of ex vivo TAMs

Postwachstum und Raumentwicklung : Denkanstöße für Wissenschaft und Praxis

Dieses von Mitgliedern des Arbeitskreises "Postwachstumsökonomien" (2016 - 2020) der ARL verfasste Positionspapier ordnet die internationale Postwachstumsdebatte ein und diskutiert ihre Relevanz für die Raumentwicklung und die raumwissenschaftliche Forschung. Neben sektoralen Zugängen und Befunden werden konkrete Vorschläge zur Postwachstumsorientierung in Planung, Forschung und Lehre gemacht. Dabei wird zwischen kurzfristig erreichbaren Veränderungen und mittel- bis langfristig auszulegenden Maßnahmen unterschieden