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http://dx.doi.org/10.1126/science.1254064 | DOI Listing |
J Clin Med
December 2024
Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia.
Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto's thyroiditis (HT) and Graves' disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal-fetal tolerance, potentially triggering or exacerbating AITD.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.
Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Citrullination, a post-translational modification (PTM), plays a critical role in rheumatoid arthritis (RA) by triggering immune responses to citrullinated self-antigens. Some HLA-DRB1 genes encode molecules with the shared epitope (QKRAA/QRRAA) sequence in the peptide-binding groove which preferentially presents citrulline-modified peptides, like vimentin, that intensifies the immune response in RA. In this study, we used computational approaches to evaluate intermolecular interactions between vimentin peptide-ligands (with/without PTM) and HLA-DRB1 alleles associated with a significantly increased risk for RA development.
View Article and Find Full Text PDFEMBO Mol Med
January 2025
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau determined in the cerebrospinal fluid (CSF).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.
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