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Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.
ACS Chem Neurosci
January 2025
School of Health & Life Sciences, Teesside University, Middlesbrough TS1 3BX, United Kingdom.
The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein.
View Article and Find Full Text PDFGut-brain axis and neuropsychiatric health: recent advances.
Sci Rep
January 2025
Affective Psychology Department, Institute of Psychology, Eötvös Loránd University, Budapest, Hungary.
The gut–brain axis, a bidirectional communication pathway, permits the central nervous system (CNS) to exert influence over gastrointestinal function in response to stress, while the gut microbiota regulates the CNS via immune, neuroendocrine, and vagal pathways. Current research highlights the importance of the gut microbiota in stress-related disorders and the need for further research into the mechanisms of gut–brain communication, with potential therapeutic implications for a wide range of health conditions. This is a challenge taken on in this Collection on the Gut-Brain Axis.
View Article and Find Full Text PDFIntegrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis.
Int J Mol Sci
December 2024
Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mammalian blood cells originate from specialized 'hemogenic' endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs.
View Article and Find Full Text PDFElucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core.
Molecules
December 2024
Department of Chemistry, William & Mary, Williamsburg, VA 23185, USA.
The development of new antibiotics with unique mechanisms of action is paramount to combating the growing threat of antibiotic resistance. Recently, based on inspiration from natural products, an asymmetrical polyacetylene core structure was examined for its bioactivity and found to have differential specificity for different bacterial species based on the substituents around the conjugated alkyne. This research further probes the structural requirements for bioactivity through a systematic synthesis and investigation of new compounds with variable carbon chain length, alkynyl subunits, and alcohol substitution.
View Article and Find Full Text PDFSite-specific seeding of Lewy pathology induces distinct pre-motor cellular and dendritic vulnerabilities in the cortex.
Nat Commun
December 2024
Weldon School of Biomedical Engineering, West Lafayette, Indiana, IN, USA.
Circuit-based biomarkers distinguishing the gradual progression of Lewy pathology across synucleinopathies remain unknown. Here, we show that seeding of α-synuclein preformed fibrils in mouse dorsal striatum and motor cortex leads to distinct prodromal-phase cortical dysfunction across months. Our findings reveal that while both seeding sites had increased cortical pathology and hyperexcitability, distinct differences in electrophysiological and cellular ensemble patterns were crucial in distinguishing pathology spread between the two seeding sites.
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