Formation of beta-amyloid plaques is a crucial feature of Alzheimer's disease. In the present work time resolved static light scattering was applied to investigate the size and shape of growing beta-amyloid aggregates preceding plaque formation. The beta-amyloid protein with 40 amino acid residues was used. Salt free buffer solutions and solutions with 0.15M NaCl at 37 degrees C served as the aggregation medium. The focus lay on the first 2h following initiation of the aggregation process which corresponds to the protofibril phase. Addition of the NaCl accelerated the aggregation process considerably. Scattering data from aggregation in saline solutions indicated formation of long fibers which suggest interpretation of data with the worm-like chain model. Two important results were revealed: (i) At the end of the time resolved recordings, the worm-like chain model provided a fully adequate picture for the growing aggregates. Chain stiffness is characterised in terms of the persistence length, which is close to 50 nm. The linear mass density of the growing fibers approached a value of two monomers per nm corresponding to single stranded fibers, which is in accordance with presently existing models for the aggregation of beta-amyloid. The fibers finally reached contour lengths of several thousand nanometers. (ii) The plateau values for the persistence length and linear mass density observed in the final regime are gradually approached from higher values. This observation is inconsistent with simple worm-like chains. Rather does it indicate existence of another species during the initial phase of the aggregation, in addition to monomers and fibers. Aside from further insight into fundamental aspects of beta-amyloid aggregation, time resolved static light scattering provides an appropriate tool for assay tests with drugs designed to interfere with the aggregation process.
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Front Genet
December 2024
School of information engineering, Jingdezhen Ceramic University, Jingdezhen, China.
The early symptoms of hepatocellular carcinoma patients are often subtle and easily overlooked. By the time patients exhibit noticeable symptoms, the disease has typically progressed to middle or late stages, missing optimal treatment opportunities. Therefore, discovering biomarkers is essential for elucidating their functions for the early diagnosis and prevention.
View Article and Find Full Text PDFMass Spectrom (Tokyo)
December 2024
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu-City, Toyama 939-0398, Japan.
Matrix-assisted laser desorption/ionization (MALDI), surface-assisted laser desorption/ionization (SALDI), and time-of-flight mass spectrometry (TOFMS) imaging are used for visualizing the spatial distribution of analytes. Mass spectrometry (MS) imaging of a sample with a rough surface with a uniform distribution of an analyte does not provide uniform ion intensities in the image. A shift in the value of the analyte ions is also observed.
View Article and Find Full Text PDFBackground Cervical cancer is the fourth most common cancer among women with significant global disparities in disease burden. In lower-resource settings, where routine screening is uncommon, delays in diagnosis and treatment contribute to morbidity and mortality. Understanding care delays may inform strategies to decrease time to treatment, improving patient outcomes.
View Article and Find Full Text PDFOver the past two decades, rapid advancements in magnetic resonance technology have significantly enhanced the imaging resolution of functional Magnetic Resonance Imaging (fMRI), far surpassing its initial capabilities. Beyond mapping brain functional architecture at unprecedented scales, high-spatial-resolution acquisitions have also inspired and enabled several novel analytical strategies that can potentially improve the sensitivity and neuronal specificity of fMRI. With small voxels, one can sample from different levels of the vascular hierarchy within the cerebral cortex and resolve the temporal progression of hemodynamic changes from parenchymal to pial vessels.
View Article and Find Full Text PDFLive human brain tissues provide unique opportunities for understanding the physiology and pathophysiology of synaptic transmission. Investigations have been limited to anatomy, electrophysiology, and protein localization-while crucial parameters such as synaptic vesicle dynamics were not visualized. Here we utilize zap-and-freeze time-resolved electron microscopy to overcome this hurdle.
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