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Digital learning and self-assessment tools have gained importance in medical education over the last years and are pushing back print media more and more. They enable flexible learning that is aligned with current state exams and the latest scientific findings. Embedded videos, interactive graphics and practice questions offer a more diverse learning experience than using books alone. While the commercial learning tools cover the state examinations’ content well, they often lack what is additionally taught in different faculties. At the same time, the dominance of a few providers is tied to rising costs for students or to provide campus licenses. Faculties may thus offer literature and learning platforms of less variety, and an intensive and broad examination of subjects and problems is made more difficult. The promotion and nationwide availability of locally initiated non-commercial learning and examination tools can counteract this development. Electronic learning platforms enable efficient exam preparation with the presentation of exam questions. Paper-based preparatory exams have already been almost completely replaced by their electronic counterparts. Digital exams offer decisive advantages over paper-based exams, for example with the embedding of video sequences and increased feasibility of sequential questions, and should become standard not only in exam preparation., Auch in der medizinischen Ausbildung treten digitale Angebote gegenüber Printmedien als Werkzeug zum Lernen immer weiter in den Vordergrund. Sie ermöglichen ein flexibles und auf aktuelle Staatsexamina und neueste wissenschaftliche Erkenntnisse abgestimmtes Lernen. Eingebettete Videos, interaktive Grafiken und Übungsfragen bieten ein vielfältigeres Lernerlebnis als die alleinige Nutzung von Büchern. Der stetigen Anpassung der Lerninhalte auf die bundesweiten Prüfungen steht bei kommerziellen Anbietern eine lückenhafte Abdeckung der nicht staatlich geprüften Inhalte gegenüber. Zugleich ist die Dominanz weniger Anbieter aufgrund steigender Kosten für die Studierenden oder zur Bereitstellung von Campuslizenzen kritisch zu bewerten. Fakultäten bieten so gegebenenfalls weitere Literatur und Lernplattformen seltener an, eine intensive und breite Auseinandersetzung mit Fächern und Problemstellungen wird erschwert. Die Förderung und bundesweite Verfügbarmachung lokal initiierter nichtkommerzieller Lern- und Prüfungstools kann dieser Entwicklung entgegenwirken. Elektronische Lernplattformen ermöglichen mit der Darstellung von Examensfragen eine effiziente Prüfungsvorbereitung. Papierbasierte Vorbereitungsklausuren wurden durch ihr elektronisches Pendant bereits nahezu vollständig ersetzt. Digitale Prüfungen bieten beispielsweise mit der Einbettung von Videosequenzen und einer besseren Umsetzbarkeit sequentieller Fragen entscheidende Vorteile gegenüber papierbasierten Klausuren und sollten nicht nur in der Prüfungsvorbereitung Standard werden.

Astrocytes are resident glia cells of the central nervous system (CNS) that play complex and heterogeneous roles in brain development, homeostasis and disease. Since their vast involvement in health and disease is becoming increasingly recognized, suitable and reliable tools for studying these cells in vivo and in vitro are of utmost importance. One of the key challenges hereby is to adequately mimic their context-dependent in vivo phenotypes and functions in vitro. To better understand the spectrum of astrocytic variations in defined settings we performed a side-by-side-comparison of embryonic stem cell (ESC)-derived astrocytes as well as primary neonatal and adult astrocytes, revealing major differences on a functional and transcriptomic level, specifically on proliferation, migration, calcium signaling and cilium activity. Our results highlight the need to carefully consider the choice of astrocyte origin and phenotype with respect to age, isolation and culture protocols based on the respective biological question.

The two-coordinate metal amide complexes V{N(SiMePh₂)₂}₂ (1) and Cr{N(SiMe₂Ph)₂}₂ (2) were synthesized by reaction of two equivalents of LiN(SiMePh₂)₂ with VI₂(THF)₄ or CrCl₂(THF)₂ in n-hexane. Their crystal structures showed that they have bent coordination, N-V-N = 137.0(4)°, N-Cr-N = 139.19(5)°, at the metals. The vanadium complex (1) displayed no tendency to isomerize as previously observed for some V(II) amido complexes. Curie fits of SQUID magnetic measurements afforded magnetic moments of 3.36 (1) and 4.68 (2) μB, consistent with high-spin configurations. These values are lower than the spin-only values of 3.88 and 4.90 μB expected for d³ and d⁴ complexes, suggesting a significant unquenched orbital angular momentum contribution to the overall moment, which is lower as a result of the positive spin-orbit coupling constants.

Rho GTPases control cell morphogenesis and thus fundamental processes in all eukaryotes. They are regulated by 145 RhoGEF and RhoGAP multi-domain proteins in humans. How the Rho signaling system is organized to generate localized responses in cells and prevent their spreading is not understood. Here, we systematically characterized the substrate specificities, localization and interactome of the RhoGEFs/RhoGAPs and revealed their critical role in contextualizing and spatially delimiting Rho signaling. They localize to multiple compartments providing positional information, are extensively interconnected to jointly coordinate their signaling networks and are widely autoinhibited to remain sensitive to local activation. RhoGAPs exhibit lower substrate specificity than RhoGEFs and may contribute to preserving Rho activity gradients. Our approach led us to uncover a multi-RhoGEF complex downstream of G-protein-coupled receptors controlling a Cdc42/RhoA crosstalk. The spatial organization of Rho signaling thus differs from other small GTPases and expands the repertoire of mechanisms governing localized signaling activity.

The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 mice that was MC-derived as verified by infection of MC-deficient KitW-sh/W-sh “sash” mutants. In these mutants, CD8 T cells were recruited less efficiently to the lungs, correlating with enhanced viral replication and delayed virus clearance. A causative role for MC was verified by MC reconstitution of “sash” mice restoring both, efficient CD8 T-cell recruitment and infection control. These results reveal a novel crosstalk axis between innate and adaptive immune defense against CMV, and identify MC as a hitherto unconsidered player in the immune surveillance at a relevant site of CMV disease., Author Summary Being strategically located beneath endothelial and epithelial surfaces, mast cells (MC) serve as sentinels for invading pathogens at host-environment boundaries as part of the innate defense against infection. Host genetic resistance against cytomegaloviruses (CMV) is largely determined by the innate immune response, but an implication of MC in the adaptive immune defense against CMV has not been considered so far and is almost impossible to address in human infection. Using murine CMV as a model that in the past has already pioneered the discovery of fundamental principles in CMV-host interactions, our data reveal MC as central part of a novel crosstalk-axis between the innate and adaptive immune response to CMV. We found that upon host infection MC become rapidly activated and promote the recruitment of protective CD8 T cells to the lungs, a noted critical site of CMV pathogenesis in humans as well as in the mouse model. Enhanced tissue infiltration of CD8 T cells results in a reduced peak viral load and a faster clearance of productive infection. Realizing the importance of MC in the control of pulmonary CMV infection may help to develop new strategies for preventing CMV pneumonia by MC supplementation in recipients of hematopoietic cell transplantation.