Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

The metabolism of serotonin in neuronal cells in culture and platelets and their role in platelet aggregation

The aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by human platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In human platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 M of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentates this phenomenon in the presence of calcium ionophore A23187. This synergistic interaction between serotonin (2–5 M) and A23187 (0.5–2 M) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 M) and cyproheptadine (IC50, 20 M)] and calcium channel blockers (verapamil and diltiazem, IC50 = 20 and 40 M, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 M. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 M) by inhibiting respiratory burst. However, neither genistein, a tyrosine-speciWc protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway

The impact of COVID-19 on globalization

Globalization has altered the way we live and earn a livelihood. Consequently, trade and travel have been recognized as significant determinants of the spread of disease. Additionally, the rise in urbanization and the closer integration of the world economy have facilitated global interconnectedness. Therefore, globalization has emerged as an essential mechanism of disease transmission. This paper aims to examine the potential impact of COVID-19 on globalization and global health in terms of mobility, trade, travel, and countries most impacted. The effect of globalization were operationalized in terms of mobility, economy, and healthcare systems. The mobility of individuals and its magnitude was assessed using airline and seaport trade data and travel information. The economic impact was measured based on the workforce, event cancellations, food and agriculture, academic institutions, and supply chain. The healthcare capacity was assessed by considering healthcare system indicators and preparedness of countries. Utilizing a technique for order of preference by similarity to ideal solution (TOPSIS), we calculated a pandemic vulnerability index (PVI) by creating a quantitative measure of the potential global health. The pandemic has placed an unprecedented burden on the world economy, healthcare, and globalization through travel, events cancellation, employment workforce, food chain, academia, and healthcare capacity. Based on PVI results, certain countries were more vulnerable than others. In Africa, more vulnerable countries included South Africa and Egypt; in Europe, they were Russia, Germany, and Italy; in Asia and Oceania, they were India, Iran, Pakistan, Saudi Arabia, and Turkey; and for the Americas, they were Brazil, USA, Chile, Mexico, and Peru. The impact on mobility, economy, and healthcare systems has only started to manifest. The findings of this study may help in the planning and implementation of strategies at the country level to help ease this emerging burden.Applied Science, Faculty ofNon UBCEngineering, School of (Okanagan)ReviewedFacultyResearcherGraduat