1,721,108 research outputs found
Hippo signaling pathway activation during SARS-CoV-2 infection contributes to host antiviral response
Get PDFSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19-associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air–liquid interface (ALI) cultures. SARS-CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin, a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19
An Investigation into a Mechanism Underlying Epidemic Dengue Virus Strains.
Get PDFMaster'sJOINT M.SC. IN INFECTIOUS DISEASES, VACCINOLOGY AND DRUG DISCOVER
Biological control of dengue and Wolbachia-based strategies. 2nd ed.
No full textThis book chapter describes a number of biological control methods that currently exist, or are under development, which target the dengue vector Aedes aegypti. These include biological agents that are natural predators of mosquito larvae, such as copepods, and entomopathogenic bacteria (Bacillus thuringiensis israelensis) and fungi. Also, the chapter reviews the transinfection of Aedes aegypti with the bacterium Wolbachia pipientis to reduce dengue virus transmission while minimizing social and environmental harm. It examines the effects of Wolbachia infection on A. aegypti, Wolbachia's ability to invade mosquito populations, community support for Wolbachia-based biological control, and future perspectives
Evaluation of location-specific predictions by a detailed simulation model of Aedes aegypti populations.
Get PDFSkeeter Buster is a stochastic, spatially explicit simulation model of Aedes aegypti populations, designed to predict the outcome of vector population control methods. In this study, we apply the model to two specific locations, the cities of Iquitos, Peru, and Buenos Aires, Argentina. These two sites differ in the amount of field data that is available for location-specific customization. By comparing output from Skeeter Buster to field observations in these two cases we evaluate population dynamics predictions by Skeeter Buster with varying degrees of customization.Skeeter Buster was customized to the Iquitos location by simulating the layout of houses and the associated distribution of water-holding containers, based on extensive surveys of Ae. aegypti populations and larval habitats that have been conducted in Iquitos for over 10 years. The model is calibrated by adjusting the food input into various types of containers to match their observed pupal productivity in the field. We contrast the output of this customized model to the data collected from the natural population, comparing pupal numbers and spatial distribution of pupae in the population. Our results show that Skeeter Buster replicates specific population dynamics and spatial structure of Ae. aegypti in Iquitos. We then show how Skeeter Buster can be customized for Buenos Aires, where we only had Ae. aegypti abundance data that was averaged across all locations. In the Argentina case Skeeter Buster provides a satisfactory simulation of temporal population dynamics across seasons.This model can provide a faithful description of Ae. aegypti populations, through a process of location-specific customization that is contingent on the amount of data available from field collections. We discuss limitations presented by some specific components of the model such as the description of food dynamics and challenges that these limitations bring to model evaluation
AN INVESTIGATION OF THE ROLE OF FC GAMMA RECEPTORS IN DENGUE VIRUS NEUTRALIZATION
No full textPh.DDOCTOR OF PHILOSOPH
A study of the Japanese Encephalitis Serogroup viruses in resident animals in Singapore, with focus on Japanese Encephalitis and West Nile/Kunjin viruses
No full textMaster'sMASTER OF SCIENC
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