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| http://dx.doi.org/10.1093/ckj/sfab171 | DOI Listing |
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Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.
PLoS Pathog
January 2025
Institute of Medical Virology, University of Zurich (UZH), Zurich, Switzerland.
For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies and neutralize with constant high potency. Comparative analysis of neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational flexibility, with substantial epitope-specific variation of bnAb potency ranging from increased to decreased activity against open, neutralization-sensitive Env. To systematically investigate the impact of variability in Env conformation on bnAb potency we screened 126 JR-CSF point mutants for generalized neutralization sensitivity to weakly neutralizing antibodies (weak-nAbs) depending on trimer opening and plasma from people with chronic HIV-1 infection.
View Article and Find Full Text PDFDo cytokines play a role in the transition from acute to chronic musculoskeletal pain?
Pharmacol Res
January 2025
University Hospital of Jena, Institute of Physiology 1, Jena D-07740, Germany. Electronic address:
Musculoskeletal pain has a high prevalence of transition to chronic pain and/or persistence as chronic pain for years or even a lifetime. Possible mechanisms for the development of such pain states are often reflected in inflammatory or neuropathic processes involving, among others, cytokines and other molecules. Since biologics such as blockers of TNF or IL-6 can attenuate inflammation and pain in a subset of patients with rheumatoid arthritis, the question arises to what extent cytokines are involved in the generation of pain in human musculoskeletal diseases.
View Article and Find Full Text PDFInsulin amyloid morphology is encoded in H-bonds and electrostatics interactions ruling protein phase separation.
J Colloid Interface Sci
December 2024
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Center for Biopharmaceuticals and Biobarriers in Drug Delivery, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address:
Ion-protein interactions regulate biological processes and are the basis of key strategies of modulating protein phase diagrams and stability in drug development. Here, we report the mechanisms by which H-bonds and electrostatic interactions in ion-protein systems determine phase separation and amyloid formation. Using microscopy, small-angle X-ray scattering, circular dichroism and atomistic molecular dynamics (MD) simulations, we found that anions specifically interacting with insulin induced phase separation by neutralising the protein charge and forming H-bond bridges between insulin molecules.
View Article and Find Full Text PDFMechanisms and pharmacotherapy of cancer cachexia-associated anorexia.
Pharmacol Res Perspect
February 2025
Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.
Cachexia is a multifactorial metabolic syndrome characterized by weight and skeletal muscle loss caused by underlying illnesses such as cancer, heart failure, and renal failure. Inflammation, insulin resistance, increased muscle protein degradation, decreased food intake, and anorexia are the primary pathophysiological drivers of cachexia. Cachexia causes physical deterioration and functional impairment, loss of quality of life, lower response to active treatment, and ultimately morbidity and mortality, while the difficulties in tackling cachexia in its advanced phases and the heterogeneity of the syndrome among patients require an individualized and multidisciplinary approach from an early stage.
View Article and Find Full Text PDFGenetically Engineered T Cells and Recombinant Antibodies to Target Intracellular Neoantigens: Current Status and Future Directions.
Int J Mol Sci
December 2024
Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Recombinant antibodies and, more recently, T cell receptor (TCR)-engineered T cell therapies represent two immunological strategies that have come to the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell-based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T cell), a chimeric antigen receptor (CAR) with the variable domains of a neoepitope-reactive TCR as a binding domain (TCR-CAR-T cell) or a TCR-like antibody as a binding domain (TCR-like CAR-T cell). Furthermore, the synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are designed as a double-chain TCRαβ-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-Cα and TCR-Cβ, respectively, resulting in TCR signaling.
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