name title fuMetaTitel body fuDCcreator fuDCcreatorLinks fuDCpublisher fuDCpublisherLocation fuDCSizeOrDuration fuDCdateYear fuDCdateMonth fuDCdateDay fuDCsubject fuDCrelationPartOf fuDCrelation fuDClanguage fuDCsource fuDCcontributor fuDCtype fuDCformat fuDCidentifier fuDCcoverage fuDCrights fuDCdescriptionDE fuDCdescriptionEN fuDCIdentifierBibliographicCitation fuBild fuDCBibtex fuLinksZumThema P4ERYPMC Blobby is a synaptic active zone assembly protein required for memory in Drosophila "Luetzkendorf, J.; Matkovic-Rachid, T.; Liu, S.; Goetz, T.; Gao, L.; Turrel, O.; Maglione, M.; Grieger, M.; Putignano, S.; Ramesh, N.; Ghelani, T.; Neumann, A.; Gimber, N.; Schmoranzer, J.; Stawrakakis, A.; Brence, B.; Baum, D.; Ludwig, Kai; Heine, M.; Mielke, T.; Liu, F.; Walter, A. M.; Wahl, M. C.; Sigrist, S. J." Nature Communications 2025 Abstract At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, ?Blobby?, essential for proper AZ nano-organization. Blobby biochemically associates with the ELKS family AZ scaffold protein Bruchpilot (BRP) and integrates into newly forming AZs. Loss of Blobby results in fewer AZs forming, ectopic AZ scaffold protein accumulations (?blobs?) and disrupts nanoscale architecture of the BRP-AZ scaffold. Functionally, blobby mutants show diminished evoked synaptic currents due to reduced synaptic vesicle release probability and fewer functional release sites. Blobby is also present in adult brain synapses, and post-developmental knockdown of Blobby in the mushroom body impairs olfactory aversive memory consolidation. Thus, our analysis identifies an additional layer of AZ regulation critical for developmental AZ assembly but also for AZ-mediated plasticity controlling behavior. https://www.nature.com/articles/s41467-024-55382-9 journalArticle 10.1038/s41467-024-55382-9 2N7L2B2I Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus "Pauletti, Alberto; Gurlo, Polina; Weiss, Edna; DePaula-Silva, Ana Beatriz; Wilcox, Karen S.; Broeer, Sonja" Frontiers in Cellular Neuroscience 2025 Infections impacting the central nervous system (CNS) constitute a substantial predisposing factor for the emergence of epileptic seizures. Given that epilepsy conventionally correlates with hippocampal sclerosis and neuronal degeneration, a potentially innovative avenue for therapeutic intervention involves fostering adult neurogenesis, a process primarily occurring within the subgranular zone of the dentate gyrus (DG) through the differentiation of neural stem cells (NSC). While experimental seizures induced by chemoconvulsants or electrical stimulation transiently enhance neurogenesis, the effects of encephalitis and the resultant virus-induced seizures remain inadequately understood. Thus, this study employed the Theiler's Murine Encephalomyelitis Virus (TMEV) model of virus-induced seizures in adult C57BL/6J mice to investigate the impact of infection-induced seizures on neurogenesis at three distinct time points [3, 7, and 14 days post-infection (dpi)]. Immunohistochemical analysis revealed a reduction in the overall number of proliferating cells post-infection. More notably, the specific cell types exhibiting proliferation diverged between TMEV and control (CTR) mice: (1) Neuronal progenitors (doublecortin, DCX +) were almost entirely absent at 3 dpi in the dorsal DG. They resumed proliferation at 14 dpi, but, did not recover to CTR levels, and displayed aberrant migration patterns. (2) The number of proliferating NSCs significantly decreased within the dorsal DG of TMEV mice at 14 dpi compared to CTR, while (3) a heightened population of proliferating astrocytes was observed. Most observed changes were not different between seizing and non-seizing infected mice. In summary, our findings demonstrate that viral infection rapidly depletes neuronal progenitor cells and causes aberrant migration of the remaining ones, potentially contributing to hyperexcitability. Additionally, the increased differentiation toward glial cell fates in infected mice emerges as a possible additional pro-epileptogenic mechanism. https://www.frontiersin.org/articles/10.3389/fncel.2024.1528918/full journalArticle 10.3389/fncel.2024.1528918 RUFYX7FV Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling "Hiepen, Christian; Benamar, Mounir; Barrasa-Fano, Jorge; Condor, Mar; Ilhan, Mustafa; Muench, Juliane; Hastar, Nurcan; Kerkhoff, Yannic; Harms, Gregory S.; Mielke, Thorsten; Koenig, Benjamin; Block, Stephan; Rocks, Oliver; Abdelilah-Seyfried, Salim; Van Oosterwyck, Hans; Knaus, Petra" Communications Biology 2025 Abstract Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis. https://www.nature.com/articles/s42003-024-07431-8 journalArticle 10.1038/s42003-024-07431-8 VE7YKUYY Synthesis of Dendritic Oligo?Glycerol Amphiphiles with Different Hydrophobic Segments to Improve their Performance as Nanocarriers "Kumari, Pooja; Zoister, Christian; Hanheiser, Natalie; Makki, Hesam; Schade, Boris; Dimde, Mathias; Achazi, Katharina; Kumar, Sumit; Haag, Rainer; Singh, Abhishek K." ChemistryOpen 2025 Abstract A new class of non?ionic dendritic amphiphiles has been developed from biobased chemicals, in particular glycerol?based dendrons coupled to commercially available acids via the Steglich esterification process. These non?ionic amphiphiles are functionalized with different hydrophobic segments to investigate the contribution of the same towards their guest transport behaviour. Therefore, different alkyl chains i.e, C8 and C12, as well as two different aromatic units were introduced as a hydrophobic segments and G1?oligo?glycerol as a hydrophilic segment. Their physicochemical properties were characterized by different techniques such as dynamic light scattering and fluorescence measurements. The results show that these amphiphiles form a very uniform micellar supramolecular structures that is independent of the hydrophobic system. The critical micelle concentration for the prepared non?ionic amphiphiles was found to be in the range of 0.3 to 1.8?mg/mL, which depend on the type of hydrophobic units. The encapsulation capacities of the amphiphiles were tested using Nile Red and Nimodipine as model dye and drug, respectively. The encapsulation studies showed a preference for C12? and pyrene?based amphiphiles through relatively different mechanisms unraveled by molecular dynamics (MD) simulations. Further, the cytotoxicity and cellular uptake of these systems as well as the release profiles were investigated. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/open.202400448 journalArticle 10.1002/open.202400448 FBCQAFHX Chloromethane?Enabled Quaternization of Linear Polyglycerol Amines and Their Application as Antibacterial Agents "Hanheiser, Natalie; Kleoff, Merlin; Achazi, Katharina; Singh, Abhishek; Riedel, Sebastian; Haag, Rainer" Macromolecular Rapid Communications 2025 Abstract In this study, the safe and scalable N ?methylation of primary amines in a linear polyglycerol (LPG) backbone structure is reported with altering molecular weight using gaseous chloromethane for the generation of quaternary ammonium groups. All polymers are subsequently analyzed for their antibacterial and antibiofilm properties against drug?resistant Staphylococcus?aureus ( S. aureus ), showing that the implementation of quaternary ammonium groups to a polymer backbone structure is an efficient way to generate new antimicrobial agents. Thereby, the molecular weight of the polymer backbone structure strongly correlates to its antibacterial effect and can be altered depending on the desired application. https://onlinelibrary.wiley.com/doi/10.1002/marc.202500111 journalArticle 10.1002/marc.202500111 CCGM6T3N Dual-Dynamic Covalently Cross-Linked Polyglycerol Hydrogels for Tumor Spheroid Culture "Feng, Jun; Ponomareva, Polina; Liu, Kunpeng; Nie, Chuanxiong; Chen, Rui; Haag, Rainer" Biomacromolecules 2025 https://pubs.acs.org/doi/10.1021/acs.biomac.4c01744 journalArticle 10.1021/acs.biomac.4c01744 AHPUNZLT The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers "Fricke, Mackenzie S.; Frometa, Magalee R.; Kerkhoff, Yannic; Bernhard, Samuel P.; Tahir, Ramat S.; Quaas, Elisa; Totten, William H.; Haag, Rainer; Achazi, Katharina; Cloninger, Mary J." Materials Advances 2025 Four generations of lactose-functionalized PAMAM dendrimers show low toxicity, proclivity for uptake, and mediation of galectin-3 inhibition of apoptosis. Glycodendrimers are useful systems for studying galectin-3 in cancer cells. , Poly(amidoamine) (PAMAM) dendrimers functionalized with ligands that are designed to interact with biological receptors are important macromolecules for the elucidation and mediation of biological recognition processes. Specifically, carbohydrate functionalized dendrimers are useful synthetic multivalent systems for the study of multivalent protein?carbohydrate interactions. For example, lactose functionalized glycodendrimers can be used to discern the function of galectins, galactoside-binding proteins that are often over-expressed during cancer progression. In order to effectively interpret cancer cellular assays using glycodendrimers, however, their properties in the presence of cells must first be assessed. Macromolecules that are taken up by cells would be expected to have access to many different cell signaling pathways and modes of action that solely extracellular macromolecules cannot utilize. In addition, macromolecules that display cellular toxicity could not be used as drug delivery vehicles. Here, we report fundamental studies of cellular toxicity, viability, and uptake with four generations of lactose functionalized PAMAM dendrimers. In all cases, the dendrimers are readily taken up by the cells but do not display any significant cellular toxicity. The glycodendrimers also increase cellular apoptosis, suggesting that they may abrogate the antiapoptotic protections afforded by galectin-3 to cancer cells. The results reported here indicate that appropriately functionalized PAMAM dendrimers can be used as nontoxic tools for the study and mediation of both extra and intracellular cancer processes. https://pubs.rsc.org/ma/article/6/10/3171-3184/854086 journalArticle 10.1039/D4MA00782D 28UVFRQA Evolution of multicellularity genes in Cyanobacteria in the lead up to the great oxidation event "Boden, Joanne S.; Nieves-Morian, Mercedes; Nuernberg, Dennis; Arevalo, Sergio; Flores, Enrique; Sanchez-Baracaldo, Patricia" Communications Biology 2025 https://www.nature.com/articles/s42003-025-09247-6 journalArticle 10.1038/s42003-025-09247-6