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Trigger factor accelerates nascent chain compaction and folding
Recent work indicates that many chaperones bind protein chains already during their translation by ribosomes. While chaperones are thought to merely “hold” the nascent protein chains, current methods cannot study their conformational changes. We simultaneously image single chaperone binding and detect nascent protein conformation. We show that the chaperone trigger factor accelerates the folding of proteins as they emerge from the ribosome and reveal the mechanism: By enhancing the polypeptide collapse, it pushes residues together. Our mechanism promotes folding to occur cotranslationally, impacts the many processes that depend on it, like cotranslational protein assembly, translation arrest mitigation, and aggregation suppression, and can help explain how trigger factor interacts with downstream chaperones and how cells produce proteins with limited errors
Advancements in non-invasive visualization of the immune environment in glioblastoma: A Systematic Review
Background: Glioblastoma is known for its highly immunosuppressive microenvironment, hindering the efficacy of immunotherapies. Noninvasive imaging like immuno-positron emission tomography (PET) offers the potential for visualizing immune dynamics within glioblastoma, potentially aiding in patient selection and treatment monitoring. This systematic review evaluates immuno-PET tracers currently under investigation for the noninvasive visualization of the immune environment in glioblastoma.Methods: A literature search was conducted in PubMed and Web of Science up to March 2025, using keywords related to glioblastoma, immuno-PET, immune compartments, and specific tracers. Studies were screened based on predefined inclusion and exclusion criteria, focusing on the development, characterization, or application of immuno-PET tracers targeting immune cells or immune checkpoint molecules in glioblastoma.Results: Nineteen studies met the inclusion criteria, exploring tracers targeting immune checkpoints and immune cell populations. Full-length antibodies demonstrated higher tumor specificity and retention compared to smaller fragments but showed longer circulation times. Peptide-based tracers and affibodies offered improved pharmacokinetics with rapid clearance and lower nonspecific uptake but encountered hurdles in ensuring adequate tumor targeting and retention. Advancements included dual-modal tracers combining PET and near-infrared fluorescence imaging for enhanced diagnostic and intraoperative applications.Conclusions: Significant progress has been made in developing immuno-PET tracers for noninvasive visualization of immune reactions in glioblastoma. Challenges persist in clinical translation due to issues like blood-brain barrier permeability and safety profiles. Continued research and clinical evaluations are essential to harness the potential of immuno-PET in improving glioblastoma diagnosis, assessment of treatment response, and guiding personalized immunotherapy strategies, ultimately aiming to enhance patient outcomes.Keywords: brain tumors; glioma; immune imaging; immuno-PET; immunotherapy