Pathogens including viruses evolve in tandem with diversity in their animal and human hosts. For , the focus is generally for understanding such coevolution on the virus spike protein, since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD). Viral sequences of the 19B (S) clade and variants of concern from different continents were investigated, with a focus on the A.29 lineage, which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how may have evolved and adapted to widely diverse populations globally. Results indicated that went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion-frameshifts in the N-terminal domain (NTD region) of the spike protein. In conclusion, we hypothesize that viral transmission during epidemics through populations of diverse genomic structures and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, explaining the emergence of novel variants and strains.
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http://dx.doi.org/10.3390/microorganisms10102017 | DOI Listing |
PLoS One
January 2025
Immunology and Immunotherapy Division, Center of Molecular Immunology (CIM), Havana, Cuba.
SARS-CoV-2 has continued spreading around the world in recent years since the initial outbreak in 2019, frequently developing into new variants with greater human infectious capacity. SARS-CoV-2 and its mutants use the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor, which has triggered several therapeutic strategies against COVID-19 relying on the use of ACE2 recombinant proteins as decoy receptors. In this work, we propose an ACE2 silent Fc fusion protein (ACE2-hFcLALA) as a candidate therapy against COVID-19.
View Article and Find Full Text PDFNeurochem Res
January 2025
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayıs, Samsun, Türkiye.
In the present study, the effects of the acetylcholinesterase (AChE) enzyme inhibitor rivastigmine (RIVA) on spike-wave discharges (SWDs), memory impairment, anxiety-like behavior, and the transient receptor potential vanilloid 1 (TRPV1) gene expression were investigated in genetic absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. After tripolar electrodes were implanted on the WAG/Rij rats' skulls, single doses of 0.125, 0.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Manganese (Mn) is an essential metal that serves as a cofactor for metalloenzymes important in moderating the glutamate/glutamine cycle and other oxidative stress pathways. Typically, Mn is acquired through the diet, however, Mn overexposure can arise through drinking inadequately treated well water or inhalation of Mn-containing industrial byproducts. Mn toxicity disrupts dopaminergic neurotransmission resulting in a Parkinsonian disorder referred to as manganism.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Although pharmacokinetics and pharmacodynamics of biotherapeutics are commonly studied through ELISAs; however, the extremely strong binding of modern antibody-based therapeutics result in background, inability of secondary antibody binding, and nonlinear response curves. The selectivity and specificity imparted through the use of liquid chromatography-targeted mass spectrometry (LC-MS/MS) allows for absolute quantitation of chosen peptides. For MODEL-AD, here we present a high-throughput workflow for absolute quantification of chimeric aducanumab from cortex and plasma of 5XFAD mice.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Douglas Research Centre/ McGill University, Montreal, QC, Canada.
Background: Altered neuronal timing and synchrony are biomarkers for Alzheimer's disease (AD) and correlate with memory impairments. Electrical stimulation of the fornix, the main fibre bundle connecting the hippocampus to the septum, has emerged as a potential intervention to restore network synchrony and memory performance in human AD and mouse models. However, electrical stimulation is non-specific and may partially explain why fornix stimulation in AD patients has yielded mixed results.
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