Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) α-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of α-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-α-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total α-syn (P=0.244), oligo-α-syn (P=0.221), or oligo-phospho-α-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated α-syn. Thus, phosphorylated α-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether α-syn can act as a marker of disease progression.
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http://dx.doi.org/10.1096/fj.10-179192 | DOI Listing |
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 PDFPLoS Negl Trop Dis
January 2025
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.
Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.
PLoS One
January 2025
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2.
View Article and Find Full Text PDFPLoS One
January 2025
Dirección General de Minería, República Dominicana.
This study investigates the geochemical characteristics of rare earth elements (REEs) in highland karstic bauxite deposits located in the Sierra de Bahoruco, Pedernales Province, Dominican Republic. These deposits, formed through intense weathering of volcanic material, represent a potentially valuable REE resource for the nation. Surface and subsurface soil samples were analyzed using portable X-ray fluorescence (pXRF) and a NixPro 2 color sensor validated with inductively coupled plasma optical emission spectrometry (ICP-OES).
View Article and Find Full Text PDFPLoS One
January 2025
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Objectives: Acute kidney injury (AKI) is a syndrome with high mortality and morbidity in part due to delayed recognition based on changes in creatinine. A marker for AKI based on a single measurement is needed and therefore the performance of a single measurement of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in patients admitted to the emergency department was tested.
Methods: Samples from the Triage study which included 6005 consecutive adult patients admitted to the emergency department were tested for pNGAL.
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