Yellow fever virus (YFV), a member of the Flaviviridae family, is an arthropod-borne virus that can cause severe disease in humans with a lethality rate of up to 60%. Since 2017, increases in YFV... Show moreYellow fever virus (YFV), a member of the Flaviviridae family, is an arthropod-borne virus that can cause severe disease in humans with a lethality rate of up to 60%. Since 2017, increases in YFV activity in areas of South America and Africa have been described. Although a vaccine is available, named strain 17D (Theiler and Smith, 1937), it is contraindicated for use in the elderly, expectant mothers, immunocompromised people, among others. To this day there is no antiviral treatment against YFV to reduce the severity of viral infection. Here, we used a circular polymerase extension reaction (CPER)-based reverse genetics approach to generate a full-length reporter virus (YFVhb) by introducing a small HiBit tag in the NS1 protein. The reporter virus replicates at a similar rate to the parental YFV in HuH-7 cells. Using YFVhb, we designed a high throughput antiviral screening luciferase-based assay to identify inhibitors that target any step of the viral replication cycle. We validated our assay by using a range of inhibitors including drugs, immune sera and neutralizing single chain variable fragments (scFv). In light of the recent upsurge in YFV and a potential spread of the virus, this assay is a further tool in the development of antiviral therapy against YFV. Show less
Archaeologists have regarded social networks as both the links through which people transmitted information and goods as well as a form of social storage creating relationships that could be drawn... Show moreArchaeologists have regarded social networks as both the links through which people transmitted information and goods as well as a form of social storage creating relationships that could be drawn upon in times of subsistence shortfalls or other deleterious environmental conditions. In this article, formal social network analytical (SNA) methods are applied to archaeological data from the late pre-Hispanic North American Southwest to look at what kinds of social networks characterized those regions that were the most enduring versus those that were depopulated over a 250-year period (A.D. 1200–1450). In that time, large areas of the Southwest were no longer used for residential purposes, some of which corresponds with well-documented region-wide drought. Past research has demonstrated that some population levels could have been maintained in these regions, yet regional scale depopulation occurred. We look at the degree to which the network level property of embeddedness, along with population size, can help to explain why some regions were depopulated and others were not. SNA can help archaeologists examine why emigration occurred in some areas following an environmental crisis while other areas continued to be inhabited and even received migrants. Moreover, we modify SNA techniques to take full advantage of the time depth and spatial and demographic variability of our archaeological data set. The results of this study should be of interest to those who seek to understand human responses to past, present, and future worldwide catastrophes since it is now widely recognized that responses to major human disasters, such as hurricanes, were “likely to be shaped by pre-existing or new social networks” (as reported by Suter et al. (Research and Policy Review 28:1–10, 2009)). Show less
