Using Great Basin cottonwoods to study climate change and evolution

The mountains of Great Basin National Park represent important “natural laboratories” for studying the ecological and evolutionary consequences of past climate change. The Cottonwood Ecology group at Northern Arizona University is interested in examining whether genetic changes in Nevada’s cottonwood populations have resulted in the adaptation of dependent organisms to new hosts

Forest gene diversity is correlated with the composition and function of soil microbial communities

The growing field of community and ecosystem genetics indicates that plant genotype and genotypic variation are important for structuring communities and ecosystem processes. Little is known, however, regarding the effects of stand gene diversity on soil communities and processes under field conditions. Utilizing natural genetic variation occurring in Populus spp. hybrid zones, we tested the hypothesis that stand gene diversity structures soil microbial communities and influences soil nutrient pools. We found significant unimodal patterns relating gene diversity to soil microbial community composition, microbial exoenzyme activity of a carbon‐acquiring enzyme, and availability of soil nitrogen. Multivariate analyses indicate that this pattern is due to the correlation between gene diversity, plant secondary chemistry, and the composition of the microbial community that impacts the availability of soil nitrogen. Together, these data from a natural system indicate that stand gene diversity may affect soil microbial communities and soil processes in ways similar to species diversity (i.e., unimodal patterns). Our results further demonstrate that the effects of plant genetic diversity on other organisms may be mediated by plant functional trait variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147191/1/pope0035.pd

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131)

Sexual differences in exploration behavior in Xenopus tropicalis?

The two sexes of a species often differ in many ways. How sexes differ depends on the selective context, with females often investing more in reproductive output and males in territory defense and resource acquisition. This also implies that behavioral strategies may differ between the two sexes, allowing them to optimize their fitness in a given ecological context. Here, we investigated whether males and females differ in their exploration behavior in an aquatic frog (Xenopus tropicalis). Moreover, we explored whether females show different behavioral strategies in the exploration of a novel environment as has been demonstrated previously for males of the same species. Our results show significant sex differences, with males exploring their environment more than females. Yet, similar to males, female exploratory behavior varied significantly among individuals and broadly fell into three categories: shy, intermediate and bold. Moreover, like in males, behavioral strategies are decoupled from morphology and performance. Our results suggest that females are more sedentary than males, with males engaging in greater risk taking by exploring novel environments more. Male and female behaviors could, however, be classified into similar groups, with some individuals being bolder than others and displaying more exploration behavior. The decoupling of morphology and performance from behavior appears to be a general feature in the species and may allow selection to act on both types of traits independently

A comparative analysis of phenylpropanoid metabolism, N utilization, and carbon partitioning in fast- and slow-growing Populus hybrid clones

The biosynthetic costs of phenylpropanoid-derived condensed tannins (CTs) and phenolic glycosides (PGs) are substantial. However, despite reports of negative correlations between leaf phenolic content and growth of Populus, it remains unclear whether or how foliar biosynthesis of CT/PG interferes with tree growth. A comparison was made of carbon partitioning and N content in developmentally staged leaves, stems, and roots of two closely related Populus hybrid genotypes. The genotypes were selected as two of the most phytochemically divergent from a series of seven previously analysed clones that exhibit a range of height growth rates and foliar amino acid, CT, and PG concentrations. The objective was to analyse the relationship between leaf phenolic content and plant growth, using whole-plant carbon partitioning and N distribution data from the two divergent clones. Total N as a percentage of tissue dry mass was comparatively low, and CT and PG accrual comparatively high in leaves of the slow-growing clone. Phenylpropanoid accrual and N content were comparatively high in stems of the slow-growing clone. Carbon partitioning within phenylpropanoid and carbohydrate networks in developing stems differed sharply between clones. The results did not support the idea that foliar production of phenylpropanoid defence chemicals was the primary cause of reduced plant growth in the slow-growing clone. The findings are discussed in the context of metabolic mechanism(s) which may contribute to reduced N delivery from roots to leaves, thereby compromising tree growth and promoting leaf phenolic accrual in the slow-growing clone

Hepatic macrophage responses in inflammation, a function of plasticity, heterogeneity or both?

peer-reviewedWith the increasing availability and accessibility of single cell technologies, much attention has been given to delineating the specific populations of cells present in any given tissue. In recent years, hepatic macrophage heterogeneity has also begun to be examined using these strategies. While previously any macrophage in the liver was considered to be a Kupffer cell (KC), several studies have recently revealed the presence of distinct subsets ofhepatic macrophages, including those distinct from KCs both under homeostatic and non-homeostatic conditions. This heterogeneity has brought the concept of macrophage plasticity into question. Are KCs really as plastic as once thought, being capable of responding efficiently and specifically to any given stimuli? Or are the differential responses observed from hepatic macrophages in distinct settings due to the presence of multiple subsets of these cells? With these questions in mind, here we examine what is currently understood regarding hepatic macrophage heterogeneity in mouse and human and examine the role of heterogeneity vs plasticity in regards to hepatic macrophage responses in settings of both pathogen-induced and sterile inflammation

Different Prey Resources Suggest Little Competition Between Non-Native Frogs and Insectivorous Birds Despite Isotopic Niche Overlap

Non-native amphibians often compete with native amphibians in their introduced range, but their competitive effects on other vertebrates are less well known. The Puerto Rican coqui frog (Eleutherodactylus coqui) has colonized the island of Hawaii, and has been hypothesized to compete with insectivorous birds and bats. To address if the coqui could compete with these vertebrates, we used stable isotope analyses to compare the trophic position and isotopic niche overlap between the coqui, three insectivorous bird species, and the Hawaiian hoary bat. Coquis shared similar trophic position to Hawaii amakihi, Japanese white-eye, and red-billed leiothrix. Coquis were about 3 ‰ less enriched in δ15N than the Hawaiian hoary bat, suggesting the bats feed at a higher trophic level than coquis. Analyses of potential diet sources between coquis and each of the three bird species indicate that there was more dietary overlap between bird species than any of the birds and the coqui. Results suggest that Acari, Amphipoda, and Blattodea made up \u3e90% of coqui diet, while Araneae made up only 2% of coqui diet, but approximately 25% of amakihi and white-eye diet. The three bird species shared similar proportions of Lepidoptera larvae, which were ~25% of their diet. Results suggest that coquis share few food resources with insectivorous birds, but occupy a similar trophic position, which could indicate weak competition. However, resource competition may not be the only way coquis impact insectivorous birds, and future research should examine whether coqui invasions are associated with changes in bird abundance

Large Effect Quantitative Trait Loci for Salicinoid Phenolic Glycosides in Populus: Implications for Gene Discovery

Genomic studies have been used to identify genes underlying many important plant secondary metabolic pathways. However, genes for salicinoid phenolic glycosides (SPGs)—ecologically important compounds with significant commercial, cultural, and medicinal applications—remain largely undescribed. We used a linkage map derived from a full‐sib population of hybrid cottonwoods (Populus spp.) to search for quantitative trait loci (QTL) for the SPGs salicortin and HCH‐salicortin. SSR markers and primer sequences were used to anchor the map to the V3.0 P. trichocarpa genome. We discovered 21 QTL for the two traits, including a major QTL for HCH‐salicortin (R2 = .52) that colocated with a QTL for salicortin on chr12. Using the V3.0 Populus genome sequence, we identified 2,983 annotated genes and 1,480 genes of unknown function within our QTL intervals. We note ten candidate genes of interest, including a BAHD‐type acyltransferase that has been potentially linked to PopulusSPGs. Our results complement other recent studies in Populus with implications for gene discovery and the evolution of defensive chemistry in a model genus. To our knowledge, this is the first study to use a full‐sib mapping population to identify QTL intervals and gene lists associated with SPGs