Candida albicans Factor H Binding Molecule Hgt1p – A Low Glucose-Induced Transmembrane Protein Is Trafficked to the Cell Wall and Impairs Phagocytosis and Killing by Human Neutrophils

Complement is a tightly controlled arm of the innate immune system, facilitating phagocytosis and killing of invading pathogens. Factor H (FH) is the main fluid-phase inhibitor of the alternative pathway. Many pathogens can hijack FH from the host and protect themselves from complement-dependent killing. Candida albicans is a clinically important opportunistic yeast, expressing different FH binding molecules on its cell surface, which allow complement evasion. One such FH binding molecule is the transmembrane protein “High affinity glucose transporter 1” (Hgt1p), involved in glucose metabolism. This study demonstrated that Hgt1p transcription and expression is induced and highest at the low, but physiological glucose concentration of 0.1%. Thus, this concentration was used throughout the study. We also demonstrated the transport of Hgt1p to the fungal cell wall surface by vesicle trafficking and its release by exosomes containing Hgt1p integrated in the vesicular membrane. We corroborated Hgt1p as FH binding molecule. A polyclonal anti-Hgt1p antibody was created which interfered with the binding of FH, present in normal human serum to the fungal cell wall. A chimeric molecule consisting of FH domains 6 and 7 fused to human IgG1 Fc (FH6.7/Fc) even more comprehensively blocked FH binding, likely because FH6.7/Fc diverted FH away from fungal FH ligands other than Hgt1p. Reduced FH binding to the yeast was associated with a concomitant increase in C3b/iC3b deposition and resulted in significantly increased in vitro phagocytosis and killing by human neutrophils. In conclusion, Hgt1p also exhibits non-canonical functions such as binding FH after its export to the cell wall. Blocking Hgt1p-FH interactions may represent a tool to enhance complement activation on the fungal surface to promote phagocytosis and killing of C. albicans

Reflexionsanlässe schaffen: Einblicke in Dortmunder Entwicklungsforschungsprojekte zur Musiklehrer*innenbildung

Für Lehramtsstudierende im Fach Musik besteht eine zentrale Herausforderung darin, sich im Laufe ihres Studiums innerhalb der Pluralität oftmals unverbunden nebeneinanderstehender fachdidaktischer Konzeptionen zu orientieren. Dabei müssen sie nicht nur mit divergierenden Zieldimensionen, sondern zudem mit unterschiedlichen Gegenstandsverständnissen umgehen. Deshalb bedarf es einer reflexiven Musiklehrer*innenbildung, die durch sorgfältig entwickelte Impulse Reflexionsprozesse initiiert und damit eigene fachdidaktische Positionierungen der Studierenden für die spätere Berufspraxis anbahnt. Im Beitrag werden Erträge der Entwicklung von hochschuldidaktischen Lehr-/Lernformaten in den BMBF-geförderten Projekten „Degree 4.0“, „K4D“ und „DoProfiL“ an der musikpädagogischen Forschungsstelle der TU Dortmund dargestellt. Die Projekte zielen auf die Förderung von Reflexionsprozessen und reflexionsbezogenen Dispositionen (wie einer reflexiven Haltung) und nehmen dabei digitale, teils videobasierte Lernsettings zum Musik-Erfinden, zum Sprechen über Musik und zur Inklusion im Musikunterricht in den Blick

European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome