Gamma Delta T Cells (γδ T Cells) in Health and Disease: In Memory of Professor Wendy Havran

Gamma delta (γδ) T cells are a small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues [...]

Human γδ T lymphocytes for immunotherapeutic strategies against cancer

γδ T lymphocytes are a numerically small subset of T cells with potent cytotoxic activity against a variety of tumor cells. Human γδ T cells expressing the Vγ9Vδ2 T cell antigen receptor recognize endogenous pyrophosphate molecules that are overproduced in transformed cells. Moreover, the intracellular accumulation of such pyrophosphates is strongly enhanced by aminobisphosphonates used in the treatment of osteoporosis and bone metastasis in certain cancer patients. A new concept of cancer immunotherapy is based on the endogenous activation of γδ T cells with aminobisphosphonates plus low-dose interleukin-2

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM. In this respect, we focus on the role of the NKG2D receptor/ligand system. NKG2D ligands are frequently expressed on GBM tumour cells and can activate NKG2D-expressing killer cells including NK cells and γδ T cells. Soluble NKG2D ligands, however, contribute to tumour escape from immunological attack. We also discuss the current immunotherapeutic strategies to improve the survival of GBM patients. Such approaches include the modulation of the NKG2D receptor/ligand system, the application of checkpoint inhibitors, the adoptive transfer of ex vivo expanded and/or modified immune cells or the application of antibodies and antibody constructs to target cytotoxic effector cells in vivo. In view of the multitude of pursued strategies, there is hope for improved overall survival of GBM patients in the future

Editorial: "Recent Advances in Gamma/Delta T Cell Biology: New Ligands, New Functions, and New Translational Perspectives"

Since their discovery in the mid-1980s, interest in the immunological significance of γδ T cells has been subject to oscillations. The initial excitement over the unexpected discovery of a second T cell receptor (TCR) was followed by years of uncertainty as to the biological importance of these ambivalent T cells. Major breakthroughs led to the identification of specific and unique antigens for the γδ TCR and accumulating evidence now shows that γδ T cells play a major role in local immunosurveillance, thereby controlling tumorigenesis. Since 2004, biannual international γδ T cell conferences are held to bring together experts in basic and clinical γδ T cell research. To make accessible and synthesize the body of knowledge that has been put together, to date, we have organized a “Research Topic” on γδ T cells consisting of a collection of original articles and focused reviews written by leading experts in the field. The idea of this Research Focus was to present the current status and “hot topics” as well as clinical perspectives on γδ T cell research

Vitamin C and Vitamin D-friends or foes in modulating γδ T-cell differentiation?

The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors, including vitamins. Vitamin C has pleiotropic functions in the immune system. It exerts antioxidant activity, can directly kill selected tumor targets, promotes early T-cell differentiation, and enhances Th1 cytokine production in mature T cells

Die Nationalparkregion als Kulisse für Regionalentwicklung - das Beispiel Nationalpark Hunsrück-Hochwald

Der im Jahr 2015 in Rheinland-Pfalz und dem Saarland eröffnete Nationalpark Hunsrück-Hochwald begeht in mehrfacher Hinsicht neue Wege: Die Ausweisung erfolgte im Zuge eines intensiven Bürgerbeteiligungsprozesses, der bis in die heutigen Steuerungsgremien hineinwirkt, und ist mit dem Ziel verbunden, in der gesetzlich verankerten Nationalparkregion einen weitreichenden Regionalentwicklungsprozess zu initiieren. Der kommunale Wille, ein Regionalmanagement für die Nationalparkregion einzurichten, verlangt nach der Analyse der vorhandenen Akteursstrukturen und ihrer Voraussetzung für eine kooperative Regionalentwicklung. Es stellt sich die Frage, welche Akteurskonstellation für das Regionalmanagement geeignet ist und wie es seiner koordinierenden Rolle vor dem Hintergrund der vorhandenen Kooperationsstrukturen sowie der Besonderheit als Nationalparkregion gerecht werden kann - Aspekte, die dieser Beitrag aufgreift.The national park Hunsrück-Hochwald was opened in 2015 in Rheinland-Pfalz and Saarland and breaks new ground in many respects. The designation of the park involved an intensive public participation process that continues to influence the management bodies of today. This is connected to the aim of initiating a far-reaching process of regional development in the legally designated national park region. To meet the local desire to establish regional management for the national park region it is necessary to undertake an analysis of existing structures of actors and related conditions for cooperative regional development. Consideration is given to which actor constellation is appropriate for regional management, how regional management can fulfil a coordinating role against the background of existing structures of cooperation, and how management can be made appropriate to the special character of the national park region

Quantification of Malalignment and Corrective Osteotomies in Patients With Malunion After Elastic Stable Intramedullary Nailing of Pediatric Forearm Fractures

PURPOSE: This study looked at postoperative malunion with restricted function after elastic stable intramedullary nailing (ESIN) in pediatric patients in their childhood or adolescence. The primary objective was to compare the magnitude of the osseous malposition to the healthy opposite side. Second, these individuals were treated with patient-specific surgical instrumentation, and functional outcomes were documented. METHODS: Patients under the age of 18 at the time of a corrective osteotomy due to a forearm malunion after initial ESIN treatment were included in this study. The healthy contralateral side was used as a reference for preoperative analysis and planning of the osteotomy. Osteotomies were performed using patient-specific guides and the direction and extent of the malunion were compared to the change in range of motion (ROM) after the operation. RESULTS: Fifteen patients met the inclusion criteria at three years after initial ESIN placement, with the most pronounced malposition in the rotational axis. The postoperative function significantly improved by 12° (pre-op: 60° ± 17; post-op: 72° ± 10) of pronation and 33° (pre-op: 43° ± 26; post-op: 76° ± 13) of supination. There was no correlation between the amount and direction of malformation and the change in ROM. CONCLUSIONS: The most noticeable malunion after forearm fractures treated with the ESIN technique is in the rotational direction. Patient-specific corrective osteotomy of pediatric forearm malunion following forearm fracture fixation with ESIN achieves significant improvement in forearm range of motion. CLINICAL RELEVANCE: The findings are clinically relevant since forearm fractures are the most common pediatric fracture, affecting a large number of patients who can benefit from the findings of this study. It has the potential to raise awareness of the significance of the accurate rotational component of intraoperative bone alignment in the ESIN procedure

Increasing the efficiency of optimized v-sba-15 catalysts in the selective oxidation of methane to formaldehyde by artificial neural network modelling

The present study investigates the possibility of improving the selective oxidation of methane to formaldehyde over V-SBA-15 catalysts in two different ways. In a classical approach of catalyst optimization, the in situ synthesis of V-SBA-15 catalysts was optimized with regard to the applied pH value. Among the set of catalysts synthesized, a higher amount of incorporated vanadium, a higher content of polymeric VOx species as well as a less ordered structure of the support material were observed by increasing the pH values from 2.0 to 3.0. An optimum in performance during the selective oxidation of methane to formaldehyde with respect to activity and selectivity was found over V-SBA-15 prepared at a pH value of 2.5. With this knowledge, we have now evaluated the possibilities of reaction control using this catalyst. Specifically, artificial neural network modelling was applied after the collection of 232 training samples for obtaining insight into the influence of different reaction parameters (temperature; gas hourly space velocity (GHSV); and concentration of O2, N2 and H2O) onto methane conversion and selectivity towards formaldehyde. This optimization of reaction conditions resulted in an outstanding high space-time yield of 13.6 kgCH2O·kgcat·h−1. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Displaying Iran In Berlin: Observations On (Missed?) Opportunities In Crisis

This article provides a critical review of the exhibition Iran: Five Millennia of Art and Culture, held at Berlin’s James-Simon-Galerie between December 2021 and March 2022. While its galleries provided a beautiful, respectful, and highly educational overview of the wider development of Persian material culture, the exhibition ultimately failed to deliver what was promised by its title, misleadingly conceptualising Iranian art and culture as unimportant after the mid-eighteenth century. Instead of taking advantage of the prestigious institutional network into which the exhibition was embedded in order to highlight the extraordinary level of resilience inherent in contemporary Iranian cultural production, Iran played into an unfavourable conceptualisation of a past golden age transitioning into an unilluminated present. This is particularly regretful in light of current global tendencies to define and assess Iranian cultural heritage and aspects of Iranian identity primarily on the basis of geopolitical arguments

Framework für interventionelle 2D-3D-Bildregistrierung multipler Objekte

Die Anzahl der interventionellen Eingriffe steigt und die Unterstützung durch robotische oder digitale Assistenzsysteme nimmt zu. Zeitgleich steigt der Informationsgehalt der diagnostischen Daten, die vor der Intervention über den Patienten erhoben werden. Der Transfer der präinterventionellen Daten in den Interventionsraum kann für Interventionalist und Assistenzsystem entscheidende Vorteile in Planung und Durchführung bedeuten. Derzeit bedeutet die interventionelle Bildgebung entweder zweidimensionale Projektionen ohne Tiefeninformation oder dreidimensionale Aufnahmen, die unter hohem Strahlungsaufwand gewonnen werden. Die interventionelle 2D-3D-Registrierung schließt diesen Informationsbruch durch die räumliche Registrierung der drei-dimensionalen präinterventionellen Daten durch eine oder mehrere Projektionen. In dieser Arbeit wird ein flexibles Bildregistrierungsframework vorgestellt, dass dreidimensionale Daten mit zweidimensionalen Aufnahmen registriert. Dazu wurde die mathematische Beschreibung der interdimensionalen Registrierung analysiert, die Komponenten identifiziert und deren Einfluss auf die Registrierungsperformanz evaluiert. Als Ergebnis der Laufzeitanalyse ist in das Framework ein hardware-beschleunigter Projektionsalgorithmus mit minimalen Datentransfer integriert. Für spezifische Anwendungen können sowohl die Komponenten, Transformationstyp, metrische Funktion und Optimierungsalgorithmus, gewählt werden, als auch die Anzahl der Objekte, die mit den Referenzaufnahmen registriert werden. Für die Instantiierung und Initialisierung des Frameworks werden weniger als eine Millisekunde benötigt, so dass für neue Aufnahmen das Framework rekonfiguriert werden kann. Es ist vollständig in die weitverbreitete open-source-Software Insight Segmentation and Registration Toolkit für die Bildverarbeitung integrierbar und funktioniert mit verschiedenen Kombinationen von Metriken und Optimierungsfunktionen. Stellvertretend wurde die erfolgreiche 2D-3D-Registrierung mit der Mutual-Information-Metrik und der Powell-Optimierungsfunktion gezeigt