Biology subjects

Stewart, S. D.

Publications and source records attributed to Stewart, S. D..

3 recordsLinked to original sources

bioRxiv2023

Reduced binding associated with resistance to Vip3Aa in the corn earworm (Helicoverpa zea)

Transgenic corn and cotton expressing Cry and Vip insecticidal proteins from the bacterium, Bacillus thuringiensis (Bt), have been a valuable tool for the management of lepidopteran pests. In 2019, a Vip3Aa-resistant strain of Helicoverpa zea (CEW-Vip-RR) was isolated from F2 screens of field populations in Texas. Characterizing the resistance mechanism in this strain is important for predicting the sustained efficacy of current commercial Bt traits and guiding the development of future transgenic traits. Resistance to insecticidal proteins in Bt traits is commonly associated with reduced toxin binding, with the exception of Vip3Aa resistance being associated to altered proteolytic processing in the insect host gut. Therefore, Vip3Aa protoxin processing was tested by incubation with midgut fluids from CEW-Vip-RR relative to a susceptible strain (CEW-SS). Finding no significant processing differences, alterations in Vip3Aa binding were tested by comparing binding of radiolabeled and biotinylated Vip3Aa toxin to midgut brush border membrane vesicles (BBMV) from CEW-Vip-RR and CEW-SS larvae. Specific Vip3Aa binding to CEW-Vip-RR BBMV in these experiments was consistently reduced when compared with CEW-SS BBMV. These results support that an altered Vip3Aa- receptor is associated with resistance in CEW-Vip-RR. Understanding this resistance mechanism could have important implications for resistance management decisions considering widespread Cry1 and Cry2 resistance in H. zea populations. IMPORTANCEHelicoverpa zea is a major crop pest in the United States that is managed with transgenic corn and cotton producing insecticidal proteins from the bacterium, Bacillus thuringiensis (Bt). However, H. zea has evolved widespread resistance to the Cry proteins produced in Bt corn and cotton, leaving Vip3Aa as the only plant incorporated protectant in Bt crops consistently providing excellent control of H. zea. The benefits provided by Bt crops will be substantially reduced if widespread Vip3Aa resistance develops in H. zea field populations. Therefore, it is important to identify resistance alleles and mechanisms that contribute to Vip3Aa resistance to ensure that informed resistance management strategies are implemented. This study is the first report of reduced binding of Vip3Aa to midgut receptors associated with resistance.

pathology↗

bioRxiv2021

When are bacteria really gazelles? Comparing patchy ecologies with dimensionless numbers

From micro to planetary scales, spatial heterogeneity--patchiness--is ubiquitous in ecological systems, defining the environments in which organisms move and interact. While this fact has been recognized for decades, most large-scale ecosystem models still use spatially averaged "mean fields" to represent natural populations, while fine-scale, spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grunbaum (2012, Interface Focus 2: 150-155) introduced a heuristic framework, based on three dimensionless ratios quantifying movement, reproduction, and resource consumption, to characterize patchy ecological interactions and identify when mean-field assumptions are justifiable. In this paper, we calculated Grunbaums dimensionless numbers for 33 real interactions between consumers and their resource patches in terrestrial, aquatic, and aerial environments. Consumers ranged in size from bacteria to blue whales, and patches lasted from minutes to millennia, spanning spatial scales of mm to hundreds of km. We found that none of the interactions could be accurately represented by a purely mean-field model, though 26 of them (79%) could be partially simplified by averaging out movement, reproductive, or consumption dynamics. Clustering consumer-resource pairs by their non-dimensional ratios revealed several unexpected dynamic similarities between disparate interactions. For example, bacterial Pseudoalteromonas exploit nutrient plumes in a similar manner to Mongolian gazelles grazing on ephemeral patches of steppe vegetation. Our findings suggest that dimensional analysis is a valuable tool for characterizing ecological patchiness, and can link the dynamics of widely different systems into a single quantitative framework.

ecology↗

bioRxiv2020

Feasibility and promise of circulating tumor DNA analysis in dogs with naturally-occurring sarcoma.

Comparative studies of naturally-occurring canine cancers have provided new insight into many areas of cancer research. The inclusion of pet dogs in the development and validation of circulating tumor DNA (ctDNA) diagnostics may be uniquely informative for human translation for many reasons, including: high incidence of certain spontaneous cancers, repeated access to blood and tumor from the same individuals during the course of disease progression, and molecular heterogeneity of naturally-occurring cancers in dogs. Here, we present a feasibility study of ctDNA analysis performed in 9 healthy dogs and 39 dogs with either benign or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At presentation, mean ctDNA tumor fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p 0.001), achieving an AUC of 0.84. ctDNA tumor fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively although this difference was not statistically significant (p 0.227). In paired analysis, ctDNA fraction decreased from 11.0% to 7.9% after resection of malignant tumors (p 0.047). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Future studies are underway to validate these findings, and further evaluate the role of ctDNA to assess burden of disease and treatment response during drug development.

genomics↗