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Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.
FEBS Open Bio
January 2025
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany.
Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.
View Article and Find Full Text PDFCutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.
J Prev Alzheimers Dis
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Clinical Memory Research Unit, Clinical Sciences in Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Sweden. Electronic address:
As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic.
View Article and Find Full Text PDFConfinement and Catalysis within Designed Peptide Barrels.
J Am Chem Soc
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School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, U.K.
protein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities.
View Article and Find Full Text PDFPotential and development of cellular vesicle vaccines in cancer immunotherapy.
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Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, 150001, China.
Cancer vaccines are promising as an effective means of stimulating the immune system to clear tumors as well as to establish immune surveillance. In this paper, we discuss the main platforms and current status of cancer vaccines and propose a new cancer vaccine platform, the cytosolic vesicle vaccine. This vaccine has a unique structure that can integrate antigen and adjuvant carriers to improve the delivery efficiency and immune activation ability, which brings new ideas for cancer vaccine design.
View Article and Find Full Text PDFMachine learning-based prognostic modeling and surgical value analysis of de novo metastatic invasive ductal carcinoma of the breast.
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Department of Radiation Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
Whether primary lesion surgery improves survival in patients with de novo metastatic breast cancer (dnMBC) is inconclusive. We aimed to establish a prognostic prediction model for patients with de novo metastatic breast invasive ductal carcinoma (dnMBIDC) based on machine learning algorithms and to investigate the value of primary site surgery. The data used in our study were obtained from the Surveillance, Epidemiology, and End Results database (SEER, 2010-2021) and the First Affiliated Hospital of Nanchang University (1st-NCUH, June 2013-June 2023).
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