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Yeager, R.

Publications and source records attributed to Yeager, R..

4 recordsLinked to original sources

Burn Wound Excision Drives Acute Hypermetabolism in Mice with Scald Burns

Hypermetabolism (elevated resting energy expenditure) is a hallmark of the pathophysiological response to burns. The contribution of wound excision to acute burn-induced hypermetabolism remains unclear. Importantly, while burn wound excision is a standard component of clinical burn care, it is not typically included in rodent models of burn injury. Here, we tested the hypothesis that burn wound excision drives the acute hypermetabolic response to burn trauma. C57BL/6J mice (n=12-18 per group; ~6-weeks old; 50% male) were acclimated to thermoneutral housing (30C) for 6-weeks. All mice underwent baseline body composition scans and metabolic phenotyping to determine total (TEE) and resting energy expenditure (REE). Mice were then randomized to either sham (control), scald burn (burn), wound excision (excision), or scald burn followed by immediate wound excision (burn+excision) groups. Burns and wound excisions involved ~15% of the body surface area. Mice then recovered for 14 days while individually housed in metabolic phenotyping cages. At day 14 post-injury, mice underwent a second body composition scan prior to euthanasia. There were no fatalities in the control or burn groups, whereas 23% (n=7) and 34% (n=11) of mice in the excision and burn+excision groups died or were euthanized during the 14-day recovery period. Male and female mice exhibited broadly similar responses to injury in terms of REE and TEE. Compared to control, REE was greater in burn (47%), excision (102%), and burn+excision groups (136%) during the first week post-injury (P<0.001 for all). Compared to control mice, wound excision (alone or following burns) resulted in a greater acute loss in body mass than burn injury alone. However, this cachectic response was more sustained in male mice compared to females. Similarly, wound excision (alone or following burns) resulted in greater bone mineral content and density loss compared to sham and burn alone in both sexes. Wound excision is a key contributor to the hypermetabolic and cachectic response to burn trauma in mice. We posit that rodent studies aiming to recapitulate burn-induced hypermetabolism and cachexia should include burn wound excision to better model the clinical sequelae to burns.

physiology↗

Wild yeast isolation by middle school students reveals features of North American oak populations of Saccharomyces cerevisiae and Kluyveromyces lactis

Features of the natural life cycle of the budding yeast Saccharomyces cerevisiae were crucial to its domestication as a laboratory experimental model, especially the ability to maintain stable haploid clones and cross them at will to combine alleles via meiosis. Stable haploidy results from mutations in HO, which encodes an endonuclease required for haploid-specific mating-type switching. Previous studies found an unexpected diversity of HO alleles among natural isolates within a small geographic area. We developed a hands-on field and laboratory activity for middle school students in Denver, Colorado, USA to isolate wild yeast from oak bark, identify species via DNA sequencing, and sequence HO from S. cerevisiae isolates. We find limited HO diversity in North American oak isolates, pointing to efficient, continuous dispersal across the continent. By contrast, we isolated the "dairy yeast", Kluyveromyces lactis, from a tree <10 m away and found that it represents a new population distinct from an oak population in an adjacent state, pointing to high genetic diversity. The outreach activity partnered middle school, high school, and university students in making scientific discoveries and can be adapted to other locations and natural yeast habitats. Indeed, a pilot sampling activity in southeast Texas yielded S. cerevisiae oak isolates with a new allele of HO and, from a nearby prickly pear cactus, a heat-tolerant isolate of Saccharomyces paradoxus.

evolutionary biology↗

Drivers of Bird Communities in an Urban Neighborhood Vary by Scale

Given the accelerated pace of global biodiversity loss and rapid urbanization, it is becoming increasingly urgent to identify ways to minimize the costs and maximize the benefits of urban environments for wild flora and fauna. For instance, it has been estimated that 48% of all bird species are experiencing population declines. One of the main drivers of these declines is habitat loss and degradation associated with urbanization. Increased urbanization necessitates a better understanding of how to conserve birds in urban areas. Although relationships between urbanization and bird communities have been explored extensively, few studies have been conducted in residential neighborhoods, and the influence of urban environmental conditions, particularly air pollution, on bird communities remains unclear. In this study, we examined relationships between bird community metrics and environmental measures related to vegetation and air pollution within a residential neighborhood at multiple spatial scales. We found that bird species richness and the average number of native species were positively related to greenness (as measured by the normalized difference vegetation index; NDVI) within 50 m, and negatively associated with ambient levels of NO2 at 200 m. Similarly, we found the Hill-Shannon diversity index was positively associated with canopy cover, but negatively associated with NO2 at 200 m. The average number of invasive bird species, however, was negatively correlated with canopy cover at 50 m. The average number of native birds was negatively related to ultrafine particle (<100 nm in diameter) concentration. Unlike native bird abundances, invasive bird abundances were not sensitive to NO2 or ultrafine particles. Thus, our research suggests that reductions in air pollution, in combination with greening efforts that increase NDVI and canopy cover via the restoration of vegetation within urban neighborhoods, are likely to increase bird diversity and the abundances of native birds while reducing the abundance of invasive birds.

ecology↗

Lineage reversion drives WNT independence in intestinal cancer

The WNT pathway is a fundamental regulator of intestinal homeostasis and hyperactivation of WNT signaling is the major oncogenic driver in colorectal cancer (CRC). To date, there are no described mechanisms that bypass WNT dependence in intestinal tumors. Here, we show that while WNT suppression blocks tumor growth in most organoid and in vivo CRC models, the accumulation of CRC-associated genetic alterations enables drug resistance and WNT-independent growth. In intestinal epithelial cells harboring mutations in KRAS or BRAF, together with disruption of p53 and SMAD4, transient TGF{beta} exposure drives YAP/ TAZ-dependent transcriptional reprogramming and lineage reversion. Acquisition of embryonic intestinal identity is accompanied by a permanent loss of adult intestinal lineages, and long-term WNT-independent growth. This work delineates genetic and microenvironmental factors that drive WNT inhibitor resistance, identifies a new mechanism for WNT-independent CRC growth and reveals how integration of associated genetic alterations and extracellular signals can overcome lineage-dependent oncogenic programs.

cancer biology↗