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Biology subjects

Young, S. J.

Publications and source records attributed to Young, S. J..

5 recordsLinked to original sources

Complete mitochondrial genomes of Arizona West Nile virus vectors, Culex quinquefasciatus and Culex tarsalis

Here we report a newly developed method utilizing long-range PCR and long-read Pacific Biosciences HiFi sequencing that successfully obtained two full-length and annotated mitochondrial genomes from Culex quinquefasciatus Say, 1823 and Culex tarsalis Coquillett, 1896, both from Maricopa County, Arizona, USA. Given the substantial burden of West Nile virus in Maricopa County over the past decade, and that these vectors are primarily responsible for spillover to human populations in the county, it is critical to better understand their distribution over time and space. This study begins to approach this need by contributing a novel approach that has resulted in the first West Nile virus vector mitochondrial genomes from Arizona. Our circular Cx. quinquefasciatus mitogenome is 15,587 bp in length, making it the first USA-based mitogenome sequenced through the AT-rich control region. The Cx. tarsalis mitochondrial genome is 16,416 bp long, longer than recently published California-based CTarK1 and Texas-based PQ585801 mitogenomes. The increased length of the Cx. tarsalis mitogenome is a result of a 905 bp insertion in the AT-rich control region, not present in the species publicly available mitogenomes. A maximum likelihood-based phylogenetic reconstruction supports the species designation of these newly-sequenced mitogenomes. The newly developed methodology offers a unique approach to study medically-important vector species around the globe, providing a solution to study populations through pooled vector pathogen surveillance programs.

genomics↗

From imaging to computational domains for physics-driven molecular biology simulations: Hindered diffusion in platelet masses

When formed in vivo, murine hemostatic thrombi exhibit a heterogeneous architecture comprised of distinct regions of densely and sparsely packed platelets. In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face - Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing large stacks of high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as a computational domain for Lattice Kinetic Monte-Carlo (LKMC) simulations. This process constitutes a computational pipeline that combines purely data-derived biological domains with physics-driven simulations to estimate how molecular movement is hindered in a hemostatic platelet mass. Using our pipeline, we estimated that the hindered diffusion rates of a globular protein range from 2% to 40% of the unhindered rate, with denser packing regions lending to lower molecular diffusivity. These data suggest that coagulation reactions rates, thrombin generation and activity, as well as platelet releasate activity may be drastically impacted by the internal geometry of a hemostatic thrombus. Author SummaryHemostasis and coagulation are two exquisitely complex, intertwined, and tightly regulated biological processes. Dysregulation of either process may lead to severe health consequences or death. Coagulation reactions have been extensively studied under static laboratory conditions, which are different from in vivo conditions. It is therefore imperative to understand if and how the chemical reactions underlying coagulation are regulated by the environment where they occur. In vivo experimentation enables us to image hemostasis, but not chemical reactions. Physics-driven molecular simulations of chemical reactions can bridge the gap, provided the physical environment is correctly represented computationally. The present work serves as a much-needed foundation for image-to-computation for physics based molecular simulations in biological domains.

systems biology↗

Species Distribution Modeling of Aedes aegypti in Maricopa County, Arizona from 2014-2020

Aedes aegypti mosquitoes, which are of great importance to public health, have recently and rapidly expanded their global range; however, little is understood about the distribution of these mosquitoes in desert environments. Trapping records for Ae. aegypti in Maricopa County, Arizona from 2014-2020 were used to construct species distribution models using Maxent. Satellite imagery and socioeconomic factors were used as predictors. Maps of predicted habitat suitability were converted to binary presence/absence maps, and consensus maps were created that represent "core" habitat for the mosquito over six years of time. Generally, population density was the most important predictor in the models while median income was the least important. This study is the first step toward understanding the distribution of the vector in a desert environment. One-Sentence SummaryThis study uses satellite imagery and socioeconomic factors to identify core habitat over six years in a desert environment.

ecology↗

Phylogenetic Analysis of St. Louis Encephalitis Virus within Two Southwestern United State Counties: a case for a bulk introduction event into the southwest United States

St. Louis Encephalitis Virus (SLEV) has been seasonally detected within the Culex spp. populations within Maricopa County, Arizona and Coachella Valley, California since an outbreak in Maricopa County in 2015. Previous work revealed that the outbreak was caused by an importation of SLEV genotype III, which had only been detected within Argentina in prior years. However, little is known about when the importation occurred or the population dynamics since its arrival into the southwestern United States. In this study, we wanted to determine if the annual detection of SLEV in Maricopa and Riverside counties is due to enzootic cycling or new importations. To address this question, we analyzed 143 SLEV genomes (138 sequenced as part of this study) using the Bayesian phylogenetic analysis software, BEAST, to estimate the date of arrival into the American Southwest and characterize the underlying population structure of SLEV. Phylogenetic clustering showed that SLEV variants circulating in Arizona and California form two distinct populations with little evidence of transmission among the two populations since the onset of the outbreak. Interestingly, the SLEV variants in Coachella Valley appear to be annually imported from a nearby source, whereas the Arizona population is locally sourced each year. Finally, the earliest representatives of SLEV genotype III in the southwestern US formed a polytomy that includes both California and Arizona samples. We propose that the initial outbreak could have resulted from an introductory population of SLEV, perhaps in one or more bird flocks migrating north in 2013, rather than a single variant introduced by one bird.

bioinformatics↗

Phylogenetic analysis of West Nile Virus in Maricopa County, Arizona: Evidence for dynamic behavior of strains in two major lineages in the American Southwest

West Nile Virus (WNV) has been detected annually in Maricopa County, Arizona, since 2003. With this in mind, we sought to determine if contemporary strains are established within the county or are annually imported. As part of this effort, we developed a new protocol for tiled amplicon sequencing of WNV to efficiently attain greater than 99% coverage of 14 WNV genomes collected directly from positive mosquito pools distributed throughout Maricopa County between 2014 and 2017. Bayesian phylogenetic analyses revealed that the contemporary genomes fall within two major lineages, NA/WN02 and SW/WN03. We found that all of the Arizona strains possessed a mutation known to be under positive selection (NS5-K314R), which has arisen independently four times. The SW/WN03 strains exhibited transient behavior, with at least 10 separate introductions into Arizona when considering both historical and contemporary strains. However, NA/WN02 strains are geographically differentiated and appear to be established in Arizona, with likely origins in New York. The clade of New York and Arizona strains looks to be the most ancestral extant lineage of WNV still circulating in the United States. The establishment of WNV strains in Maricopa County provides the first evidence of local overwintering by a WNV strain over the course of several years in Arizona.

evolutionary biology↗