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A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.
Proc 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.
View Article and Find Full Text PDFInternal structural changes in age-related curved hair due to cyclical extension: An IR spectroscopy study.
Int J Cosmet Sci
January 2025
Department of Engineering Science, Osaka Electro-Communication University, Neyagawa, Japan.
Objective: This study aimed to identify structural changes in age-related curved hair (referred to as "YUGAMI" hair in Japanese) induced by cyclical extension using infrared (IR) spectroscopy coupled with chemometrics, such as multivariate curve resolution (MCR) and two-dimensional correlation spectroscopy (2DCOS).
Methods: The hair fibres were stretched at a strain level of 0.3-N, and this operation was counted as one cycle and was repeated 500 cycles.
Pseudo-Phosphorylated Tau Forms Paired Helical Filaments in the Presence of High-Curvature Cholesterol-Containing Lipid Membranes.
J Am Chem Soc
January 2025
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
The tau protein misfolds in neurodegenerative diseases such as Alzheimer's disease (AD). These pathological tau aggregates are associated with neuronal membranes, but molecular structural information about how disease-like tau fibrils interact with the lipid membrane is scarce. Here, we use solid-state NMR to investigate the structure of a tau construct bearing four AD-relevant phospho-mimetic mutations (4E tau) with cholesterol-containing high-curvature lipid membranes, which mimic the membrane of synaptic vesicles in neurons.
View Article and Find Full Text PDFAn immunohistochemical study of thanatophoric dysplasia type 1 after fetus autopsy examination.
Congenit Anom (Kyoto)
January 2025
Department of Histology and Embryology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece.
The current case report presents the postmortem examination findings of a 17-week-old female fetus displaying thanatophoric dysplasia type 1 (TD-1) due to a known fibroblast growth factor receptor 3 (FGFR3) gene mutation. Gross and X-ray examination revealed significant abnormalities, including skeletal malformations with prominent TD-1 femur curvature. Microscopical evaluation indicated inadequate histological growth for the gestational age, with specific organ immaturity noted in multiple hematoxylin and eosin sections from internal organs, bone from epiphyses and diaphyses levels.
View Article and Find Full Text PDFBackground: This study evaluated the long surgical gauze (SurG) technique as a liver retraction method in laparoscopic sleeve gastrectomy (LSG). Traditional methods involve the Nathanson retractor, associated with ischemia and necrosis complications. In addition, these techniques require an additional trocar with an incision that increases postoperative pain.
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