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Biology subjects

Anderson, S. J.

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

5 recordsLinked to original sources

United States PRRSV 1-4-4 L1C.5 isolate demonstrates similar pathogenicity to a historic Chinese highly pathogenic PRRSV

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economic and animal health burden on the United States swine industry due to morbidity- and mortality-associated losses affecting all stages of pig production. Currently, a large proportion of losses are attributed to a highly virulent PRRSV strain, PRRSV 1-4-4 L1C.5. To benchmark the virulence of PRRSV 1-4-4 L1C.5, a study was conducted to compare pathogenicity of this contemporary strain to a historical Chinese highly pathogenic PRRSV (HP-PRRSV) strain, JXwn06, that devastated the Chinese and other Asian swine industries since 2006, as well as a moderately virulent United States PRRSV strain, MN184, considered to be one of the most virulent PRRSV strains circulating in the United States in the early 2000s. Weaned pigs were inoculated with PRRSV strains L1C.5, JXwn06, MN184, or mock inoculum and necropsied at 2, 6, and 10 days post inoculation, or as needed due to severe disease. Clinical metrics, viral loads, cytokine concentrations, PRRSV-specific antibody concentrations, and pathology were compared between treatment groups to compare pathogenicity. Results indicate a high degree of similarity disease dynamics between L1C.5 and JXwn06 animals that diverged from MN184 and mock animals. Findings indicate L1C.5 and JXwn06 cause more severe morbidity and mortality in weaned pigs than MN184. Results may be applied to develop more effective strategies for mitigating PRRSV 1-4-4 L1C.5 outbreaks currently plaguing the United States swine industry.

microbiology↗

Genomic correlates for migratory direction in a free-ranging cervid

Animal migrations are some of the most ubiquitous and one of the most threatened ecological processes. A wide range of migratory behaviours occur in nature, and this behaviour is not uniform between and within species, where even individuals in the same population can exhibit differentiation. While the environment largely drives migratory behaviour, it is necessary to understand the genetic mechanisms influencing migration to elucidate the adaptive potential of migratory species to cope with novel conditions and adapt to environmental change. In this study, we identified genes associated with migratory traits by undertaking pooled genome-wide scans on a natural population of a facultatively migrating ungulate. We identified genomic regions associated with variation in migratory direction in the study population, including FTM1, a gene linked to the formation of lipids, and DPPA3, a gene linked to epigenetic modifications of the maternal line. Such a genetic basis for migratory traits can have implications on heritability of behaviour and the flexibility of individuals to change their behaviour in the face of stochastic changes in their environment.

genomics↗

Integrating Subclonal Response Heterogeneity to Define Cancer Organoid Therapeutic Sensitivity

Tumor heterogeneity is predicted to confer inferior clinical outcomes, however modeling heterogeneity in a manner that still represents the tumor of origin remains a formidable challenge. Sequencing technologies are limited in their ability to identify rare subclonal populations and predict response to the multitude of available treatments for patients. Patient-derived organotypic cultures have significantly improved the modeling of cancer biology by faithfully representing the molecular features of primary malignant tissues. Patient-derived cancer organoid (PCO) cultures contain numerous individual organoids with the potential to recapitulate heterogeneity, though PCOs are most commonly studied in bulk ignoring any diversity in the molecular profile or treatment response. Here we demonstrate the advantage of evaluating individual PCOs in conjunction with cellular level optical metabolic imaging to characterize the largely ignored heterogeneity within these cultures to predict clinical therapeutic response, identify subclonal populations, and determine patient specific mechanisms of resistance.

cancer biology↗

Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks

Anomalous diffusion in crowded and complex environments is widely studied due to its importance in intracellular transport, fluid rheology and materials engineering. Specifically, diffusion through the cytoskeleton, a network comprised of semiflexible actin filaments and rigid microtubules that interact both sterically and via crosslinking, plays a principal role in viral infection, vesicle transport and targeted drug delivery. Here, we elucidate the impact of crosslinking on particle diffusion in composites of actin and microtubules with actin-actin, microtubule-microtubule and actin-microtubule crosslinking. We analyze a suite of complementary transport metrics by coupling single-particle tracking and differential dynamic microscopy. Using these orthogonal techniques, we find that particles display non-Gaussian and non-ergodic subdiffusion that is markedly enhanced by cytoskeletal crosslinking of any type, which we attribute to suppressed microtubule mobility. However, the extent to which transport deviates from normal Brownian diffusion depends strongly on the crosslinking motif - with actin-microtubule crosslinking inducing the most pronounced anomalous characteristics - due to increased actin fluctuation heterogeneity. Our results reveal that subtle changes to actin-microtubule interactions can have dramatic impacts on diffusion in the cytoskeleton, and suggest that less mobile and more locally heterogeneous networks lead to more strongly anomalous transport.

biophysics↗

Genomic architecture of artificially and sexually selected traits in a wild cervid

Characterization of the genomic architecture of fitness-related traits such as body size and male ornamentation in mammals provides tools for conservation and management: as both indicators of quality and health, these traits are often subject to sexual and artificial selective pressures. Here we performed high-depth whole genome re-sequencing on pools of individuals representing the phenotypic extremes in our study system for antler and body size in white-tailed deer (Odocoileus virginianus). Samples were selected from a tissue repository containing phenotypic data for 4,466 male white-tailed deer from Anticosti Island, Quebec, with four pools representing the extreme phenotypes for antler and body size in the population, after controlling for age. Our results revealed a largely panmictic population, but detected highly diverged windows between pools for both traits with high shifts in allele frequency (mean allele frequency difference of 14% for and 13% for antler and body SNPs in outlier windows). These regions often contained putative genes of small-to-moderate effect consistent with a polygenic model of quantitative traits. Genes in outlier antler windows had known direct or indirect effects on growth and pathogen defence, while body genes, overall GO terms, and transposable element analyses were more varied and nuanced. Through qPCR analysis we validated both a body and antler gene. Overall, this study revealed the polygenic nature of both antler morphology and body size in free-ranging white-tailed deer and identified target loci for additional analyses.

genomics↗