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Biology subjects

Young, A. C.

Publications and source records attributed to Young, A. C..

3 recordsLinked to original sources

Burning down the mouse: Effects of wildfire and post-fire reseeding on Sin Nombre virus prevalence in its reservoir host

Worldwide, physical habitats and biological communities are being reshaped by wildfire. Such changes have obvious potential to alter pathogen ecology, yet few studies, outside of those focused on ectoparasites, have tested the effects of wildfire on pathogen prevalence in wildlife. Even fewer have focused on the impacts of strategies for post-fire remediation on pathogen circulation. Here, we investigated the effect of wildfire and wildfire mitigation on the prevalence and viral load of Sin Nombre virus (SNV) infection in its reservoir host, the western deer mouse, using a study design of matched burned, unburned, and post-burn reseeded sites in northern New Mexico. In total, we screened 411 individual deer mice for SNV via RT-qPCR and analyzed the effect of wildfire and wildfire mitigation on relative mouse abundance, individual infection probability, site-level prevalence and viral load. Relative abundance was highest at reseeded sites, and model selection indicated that habitat structure, particularly the gradient from closed canopy to open-herbaceous habitat, was consistently associated with increased relative abundance. Similarly, SNV prevalence was significantly higher in reseeded sites than either burned or unburned sites but did not differ in burned versus unburned sites. Viral load did not differ between burn history types, and zero-inflated gamma hurdle models did not identify any strong predictors of viral load. Serendipitously, we were also able to investigate the impacts of an El Nino Southern Oscillation (ENSO) cycle on patterns of infection in a subsample of sites that were studied during and one year after an ENSO year and found that SNV prevalence increased significantly post-ENSO. Both reseeding and ENSO deliver resource pulses that can support increases in mouse density and thereby enhance SNV transmission. The impacts of post-fire management practices on SNV prevalence in its reservoir host that were revealed in this study should be considered when implementing such strategies and when utilizing treated areas.

ecology↗

The formation and propagation of human Robertsonian chromosomes

Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level paves the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.

genomics↗

Mitochondrial Fatty Acid Synthesis and Mecr Regulate CD4+ T Cell Function and Oxidative Metabolism

SummaryWe show that the mitochondrial fatty acid synthesis gene Mecr shapes CD4+ T cell metabolism and function. It may be targeted in inflammatory diseases and provides rationale to consider the immunological state of patients with mitochondrial disease. Lipid metabolism is fundamental to CD4+ T cell metabolism yet remains poorly understood across subsets. Therefore, we performed targeted in vivo CRISPR/Cas9 screens to identify lipid-associated genes essential for T cell subset functions. These screens established mitochondrial fatty acid synthesis (mtFAS) genes Mecr, Mcat and Oxsm as highly impactful. Of these, the inborn error of metabolism gene Mecr was most dynamically regulated. Effector and memory T cells were reduced in Mecrfl/fl; Cd4cre mice, and MECR was required for activated CD4+ T cells to efficiently proliferate, differentiate, and survive. Mecr-deficient T cells also had decreased mitochondrial respiration, reduced TCA intermediates, and accumulated intracellular iron, which contributed to cell death and sensitivity to ferroptosis. Importantly, Mecr-deficient T cells exhibited fitness disadvantages in inflammatory, tumor, and infection models. mtFAS and MECR thus play important roles in activated T cells and may provide targets to modulate immune functions in inflammatory diseases. The immunological state of MECR- and mtFAS-deficient patients may also be compromised.

immunology↗