83 research outputs found

    Wesprim-Plattenseee 2023 Kulturhauptstadt Europas

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    Der Titel „Kulturhauptstadt Europas“ als historisch einmalige Chance gibt Wesprim und der Bakony-Plattensee-Region die Möglichkeit, die Vielfalt und die Gemeinsamkeiten europĂ€ischer Kulturen und die gemeinsame europĂ€ische Zugehörigkeit zu prĂ€sentieren

    STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles

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    The centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two centrosomes of a cell during interphase into one microtubule-organizing center. This coupling is important for cell migration, cilia formation, and timing of mitotic spindle formation. Very little is known about the structure of the centrosome linker. Here, we used stimulated emission depletion (STED) microscopy to show that each C-Nap1 ring at the proximal end of the two centrioles organizes a rootletin ring and, in addition, multiple rootletin/CEP68 fibers. Rootletin/CEP68 fibers originating from the two centrosomes form a web-like, interdigitating network, explaining the flexible nature of the centrosome linker. The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart. Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75-nm intervals. The N-to-C distance of two rootletin molecules is ∌35 to 40 nm, leading to an estimated minimal rootletin length of ∌110 nm. CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. Thus, the centrosome linker consists of a vast network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as filament modulator

    Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation

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    Mouse cells package heterochromatin into compact foci. Erdel et al. show that these foci lack hallmarks of liquid droplets and rather resemble collapsed polymer globules. Their size, accessibility, and compaction are independent of HP1. They can adopt two distinct folding states that possibly represent the fundamental modes of chromatin compaction

    A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.

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    A20 is a ubiquitin-modifying protein that negatively regulates NF-ÎșB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. A20∆CNS-EC mice showed increased numbers of CNS-infiltrating immune cells during neuroinflammation and in the steady state. While the integrity of the blood-brain barrier (BBB) was not impaired, we observed a strong activation of CNS-ECs in these mice, with dramatically increased levels of the adhesion molecules ICAM-1 and VCAM-1. We discovered ICOSL as adhesion molecule expressed by A20-deficient CNS-ECs. Silencing of ICOSL in CNS microvascular ECs partly reversed the phenotype of A20∆CNS-EC mice without reaching statistical significance and delayed the onset of EAE symptoms in wildtype mice. In addition, blocking of ICOSL on primary mouse brain microvascular endothelial cells (pMBMECs) impaired the adhesion of T cells in vitro. Taken together, we here propose that CNS EC-ICOSL contributes to the firm adhesion of T cells to the BBB, promoting their entry into the CNS and eventually driving neuroinflammation

    The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination

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    Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies. Methods Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens. Results MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse. Conclusion Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies

    Den mit FrĂŒchten gefĂ€llten Baum in seiner BlĂŒthe, Entschattete mit wenigen Bey der Brusst Des Weyland Hoch-Edlen, Großachtbahren und Wohlgelahrten Herrn Herrn Johann Gottlob Schlegels, Vornehmen des Raths, wie auch bey den Cottbußischen Stadt-Judicio Wohlbestellten Secretarii Adiuncti, Nachdem solcher den 14ten Julii 1737. im 27ten Jahre seines Alters Der HochbestĂŒrtzten Wittwe zu frĂŒh, Denen HochbetrĂŒbten Eltern zu zeitig, Denen Mitleydenden Freunden zu geschwinde Gesuncken, gebrochen, gefallen

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    GedÀchtnisgedicht auf Johann Gottlob Schlegel, SekretÀr, +14. Juli 1737Ein im Leben dem Wohlseeligen vertrauter Academischer Freund Johann Gottlob Engelhardt, Rever. Minist. CandidatusAutopsie nach dem Exemplar der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Franckfurth an der Oder, gedruckt bey Philipp Schwartzen, Königl. Univ. Buchdr. - Erscheinungsjahr nach Datierung im Tite
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