The extraction of white croaker skeletal myofibrils with KI rendered a residue in which a network of longitudinal and transverse filaments could be observed by scanning electron microscopy. A trypsin-like serine proteinase isolated from the same muscle was able to produce a complete and rapid disruption of the network, while major myofibrillar proteins were only slightly modified. This fact suggests that the disassembly of the cytoskeletal network may be an early event in the proteolysis of myofibrils. Desmin was not attacked by the proteinase under the assayed conditions, which indicates that some other unidentified component of the network would be the primary target of the action of the enzyme on myofibrils.
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http://dx.doi.org/10.1016/0003-9861(89)90580-8 | DOI Listing |
J Immunother Cancer
January 2025
Internal Medicine I, Ulm University Hospital, Ulm, Germany
Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.
View Article and Find Full Text PDFmBio
January 2025
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Many bacterial toxins exert their cytotoxic effects by enzymatically inactivating one or more cytosolic targets in host cells. To reach their intracellular targets, these toxins possess functional domains or subdomains that interact with and exploit various host factors and biological processes. Despite great progress in identifying many of the key host factors involved in the uptake of toxins, significant knowledge gaps remain as to how partially characterized and newly discovered microbial toxins exploit host factors or processes to intoxicate target cells.
View Article and Find Full Text PDFFront Parasitol
March 2024
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional [CINVESTAV-Instituto Politécnico Nacional (IPN)], Mexico City, Mexico.
The retromer is a highly conserved eukaryotic complex formed by the cargo selective complex (CSC) and the sorting nexin (SNX) dimer subcomplexes. Its function is protein recycling and recovery from the endosomes to conduct the target molecules to the trans-Golgi network or the plasma membrane. The protozoan responsible for human amoebiasis, , exhibits an active membrane movement and voracious phagocytosis, events in which the retromer may be fully involved.
View Article and Find Full Text PDFMol Psychiatry
January 2025
Icahn School of Medicine at Mount Sinai, Departments of Neuroscience, Psychiatry; Addiction Institute of Mount Sinai, New York, NY, USA.
Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.
View Article and Find Full Text PDFiScience
January 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
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