Wissenschaftliche Gesellschaft Freiburg

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    Pore size independent particle size control of mesoporous N‐doped carbon nanospheres for 3D bottom‐up electrode design

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    The rational design of electrodes is crucial for improving electrochemical energy storage and conversion devices. High-performance devices require porous carbon electrodes with controlled intraparticle properties — such as morphology, size, porosity, elemental composition, and graphitic microstructure — and interparticle features like electrode-level porosity, percolation pathways, and tortuosity, that influence mass transport. Here, mesoporous N-doped carbon (MPNC) nanospheres with independently tunable particle size at a fixed pore size is reported. Extending the previously established synthesis toolbox, independent control over particle and pore sizes is demonstrated. Using a 9 nm SiO2 hard template, particle sizes between 50 and 300 nm is adjusted while maintaining comparable physicochemical properties. These MPNC nanospheres are evaluated as supercapacitor electrodes in coin cells using 1.0 m LiPF6 in EC/DEC as electrolyte. The highest specific capacitance — 67 F g−1 at 0.1 A g−1 — is obtained with the largest particles, attributed to reduced tortuosity and improved electrode percolation. As all samples exhibited similar surface areas (≈950 m2 g−1), performance differences highlight particle size-dependent diffusion limitations. This study establishes a bottom-up approach for engineering electrode architectures, enabling independent control of pore and particle sizes of MPNC nanospheres and providing a platform to systematically investigate their effects on electrochemical performance

    In vitro characterization of the aromatic SAM-dependent C-methyltransferase NapB5

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    Aromatic polyketide synthase (PKS) products undergo diverse tailoring reactions in the biosynthesis of natural products. S-Adenosyl-l-methionine (SAM)-dependent C-methyltransferases (C-MTs) play a key role in this diversification. In the biosynthesis of napyradiomycins, the C-MT NapB5 from Streptomyces aculeolatus catalyzes the C2 monomethylation of an 1,3,6,8-tetrahydroxynaphthalene (T4HN) building block. Biochemical characterization reveals that NapB5 exhibits chemoselective C-dimethylation activity in vitro, accepting both T4HN and its oxidized derivative flaviolin as substrates. Structure-guided mutagenesis and docking studies suggest that precise substrate positioning governs the enzyme’s regio- and chemoselectivity. The proximity between the nucleophilic carbon and the SAM methyl donor is crucial for this selectivity. Furthermore, comparative gene cluster analysis identifies homologous C-MTs in other actinomycetes, underscoring their role in diversifying naphthoquinone-based meroterpenoid natural products

    Prospective video-based analysis of coronal lower limb alignment may be as accurate as radiography in children

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    Temporary hemiepiphysiodesis is a growth-guided surgical technique to address lower limb malalignment in children with remaining growth potential. It is a minimally invasive approach that relies on full standing radiography of the lower limb, resulting in exposure to ionizing radiation. Radiation-free, video-based alternative techniques have recently evolved which seem to have potential to be applied in clinical pathways, but they are still very expensive and have a complex setup.In this prospective pilot study, a low budget and uncomplicated method to assess malalignment of the lower limb was compared to radiologic measurements in 40 children aged from 8 to 16 years with idiopathic genu varum or valgum. Dynamic and static video-based assessments of the children were conducted, during their routine visits provided they had undergone full standing radiographs of the lower limb. Measurements of the primary (HKA = hip-knee angle) and secondary knee angles (e.g. medial proximal tibia angle) were compared. It was observed that the video-based hip-knee-ankle angle correlated very closely with radiographic values, as well as a significant positive correlation (p Concerning the HKA, this low-budget technique may represent a reliable alternative for longitudinal evaluation of lower limb malalignment in children. Considering the measurement errors in video-based analyses, it may be suggested that radiographic follow-up is only indicated until the target HKA approximates 2°. In summary, this novel technique has the potential to be the first step towards implementing radiation-free setups within clinical routine to evaluate lower limb malalignment. Future studies will need to determine whether the reliability and quality of video-based techniques are high enough to guide operative decision making

    Characterization of cytoskeleton and vesicle trafficking abnormalities in inborn errors of immunity

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    Actin cytoskeleton rearrangement, vesicle trafficking, and autophagy are essential mechanisms contributing to the proper development, function, and homeostasis of the immune system. Genetic disruption of these processes in immune cells can lead to immunodeficiency or immune dysregulation, as observed in several inborn errors of immunity (IEI). This study focused on the pathomechanisms of three distinct IEIs: LRBA deficiency, CTLA-4 insufficiency, and ARPC5 deficiency. We revealed that LRBA coordinates multiple cellular processes beyond its previously recognized role in CTLA-4 recycling. LRBA acts as a regulator of autophagy by interacting with the autophagy proteins PIK3R4, UVRAG, and FYCO1 to facilitate the formation of autophagosomes, their intracellular movement, and their fusion with lysosomes. As autophagy supports antigen presentation via the fusion of autophagosomes with MHC-II containing vesicles, defective cargo degradation in the absence of LRBA resulted in enhanced antigen presentation and T-cell-driven inflammation (Paper I). Additionally, we demonstrated that LRBA interacts with non-muscle myosin IIA and regulates critical cytoskeleton-dependent functions in B cells, such as migration, immune synapse formation, BCR signaling, and antigen internalization (Paper II). These two novel identified roles of LRBA, beyond CTLA-4 trafficking, may explain the increased disease severity of LRBA deficiency compared to CTLA-4 insufficiency. Moreover, we improved a currently available CTLA-4 transendocytosis assay for the diagnosis of CTLA-4 insufficiency. Our test provides increased signal detection, reduced inter-assay variability, and allows compatibility with cryopreserved samples (Paper III). This improved diagnostic assay enables the accurate functional classification of CTLA4 variants of uncertain significance and supports the proper diagnosis of patients with CTLA-4 insufficiency.Finally, we identified a novel inborn error of immunity affecting the ARP2/3 complex, known as ARPC5 deficiency. This patient suffered from severe infections, congenital heart disease, and persistent diarrhea, and died at the age of three months. Loss of ARPC5 in human cells affects actin organization and function, and Arpc5-/- mice show incomplete embryonic development, indicating that ARPC5 is crucial for embryonic development and postnatal immune signaling (Paper IV).Taken together, our findings demonstrate that studying molecular pathways of inborn errors of immunity provides fundamental insights into cell biology in general and specific protein functions in health and disease, while simultaneously advancing diagnosis and treatments of patients suffering from these conditions

    Bartholin gland carcinoma: a state-of-the-art review of epidemiology, histopathology, molecular testing, and clinical management

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    Bartholin gland carcinoma (BGC) is a rare malignancy, comprising 3–7% of vulvar cancers and 40% of cases, with histotype influencing prognosis. Adenocarcinoma and node-positive disease independently predict worse survival. Treatment hinges on complete surgical excision with 2–3 mm margins, bilateral groin evaluation, and histology-tailored adjuvant therapy. Emerging data support the use of immune checkpoint inhibitors in squamous BGC and targeted agents (e.g., mTOR/CDK4/6 inhibitors) in adenocarcinoma. We propose a practical molecular testing algorithm and highlight the urgent need for prospective, multinational collaboration to establish BGC-specific guidelines

    veneeR: Quantifizierung und Kartierung des Furnierholzvolumens von Rotbuchen im stehenden Bestand auf Basis terrestrischer Laserscan-Daten

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    Wir haben ein automatisiertes, zerstörungsfreies Verfahren entwickelt, um das nutzbare Furnierholzvolumen stehender Rotbuchen (Fagus sylvatica L.) anhand von 3D-Punktwolken aus terrestrischem Laserscanning (TLS) zu schätzen und zu kartieren. Ziel war es, das Potenzial der Buchenholzverwendung, insbesondere für langlebige Produkte wie Bauholz (LVL), präzise zu erfassen.Holz spielt eine zentrale Rolle für den Klimaschutz, als langfristiger Kohlenstoffspeicher und Ersatz fossiler Baustoffe. Angesichts sinkender Holzverfügbarkeit bei der Fichte gewinnt die Buche als Bauholz zunehmend an Bedeutung.Wir präsentieren einen Ansatz zur Erfassung des Furnierholzpotenzials in Buchenwäldern. Die Punktwolken basieren auf TLS-Daten aus drei Versuchsflächen mit je zwei Behandlungsvarianten (mäßige vs. intensive Durchforstung) und unterschiedlichen Bestandesgrundflächen (25–36 m²/ha). In den Stamm-Punktwolken wurden automatisch verschiedene Konfigurationen von Furnierrollen eingepasst; die volumetrisch beste Konfiguration wurde ausgewählt. Ein Optimierungsalgorithmus verhinderte überlappende oder falsch platzierte Rollen und konnte gleichzeitig den Furnierrollenradius erhöhen.Auf Einzelbaumebene war das Furnierholzvolumen in stark durchforsteten Beständen höher. Auf Bestandesebene zeigten mäßig durchforstete Flächen das höhere Gesamtvolumen, jedoch war der Furnierholzanteil in stark durchforsteten Beständen größer. Wichtige Einflussfaktoren auf das Furnierholzvolumen eines Baums waren Brusthöhendurchmesser, Kronenansatzhöhe, Stammdurchmesserverlauf und Krümmungstiefe.Unser Ansatz identifiziert alle Bäume mit Furnierholzpotenzial und liefert direkt das Volumen unter Rinde als Tabelle und Karte. Dies ermöglicht eine präzise und anpassbare Planung der Holznutzung für hochwertige Furnierprodukte

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