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)

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

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

Biology and Impacts of Pacific Island Invasive Species: 8. Eleutherodactylus planirostris, the Greenhouse Frog (Anura: Eleutherodactylidae)

The greenhouse frog, Eleutherodactylus planirostris, is a direct-developing (i.e., no aquatic stage) frog native to Cuba and the Bahamas. It was introduced to Hawaii via nursery plants in the early 1990s and then subsequently from Hawaii to Guam in 2003. The greenhouse frog is now widespread on five Hawaiian Islands and Guam. Infestations are often overlooked due to the frog’s quiet calls, small size, and cryptic behavior, and this likely contributes to its spread. Because the greenhouse frog is an insectivore, introductions may reduce invertebrates. In Hawaii, the greenhouse frog primarily consumes ants, mites, and springtails, and obtains densities of up to 12,500 frogs ha-1. At this density, it is estimated that they can consume up to 129,000 invertebrates ha-1 night-1. They are a food source for the non-native brown tree snake in Guam and may be a food source for other non-native species. They may also compete with other insectivores for available prey. The greatest direct economic impacts of the invasions are to the nursery trade that must treat infested shipments. Although various control methods have been developed to control frogs in Hawaii, and citric acid, in particular, is effective in reducing greenhouse frogs, the frog’s inconspicuous nature often prevents populations from being identified and managed

Sex-related differences in aging rate are associated with sex chromosome system in amphibians

Sex-related differences in mortality are widespread in the animal kingdom. Although studies have shown that sex determination systems might drive lifespan evolution, sex chromosome influence on aging rates have not been investigated so far, likely due to an apparent lack of demographic data from clades including both XY (with heterogametic males) and ZW (heterogametic females) systems. Taking advantage of a unique collection of capture-recapture datasets in amphibians, a vertebrate group where XY and ZW systems have repeatedly evolved over the past 200 million years, we examined whether sex heterogamy can predict sex differences in aging rates and lifespans. We showed that the strength and direction of sex differences in aging rates (and not lifespan) differ between XY and ZW systems. Sex-specific variation in aging rates was moderate within each system, but aging rates tended to be consistently higher in the heterogametic sex. This led to small but detectable effects of sex chromosome system on sex differences in aging rates in our models. Although preliminary, our results suggest that exposed recessive deleterious mutations on the X/Z chromosome (the "unguarded X/Z effect") or repeat-rich Y/W chromosome (the "toxic Y/W effect") could accelerate aging in the heterogametic sex in some vertebrate clades.Peer reviewe

Longitudinal in vivo bioimaging of hepatocyte transcription factor activity following cholestatic liver injury in mice

© The Author(s) 2017.Molecular mechanisms regulating liver repair following cholestatic injury remain largely unknown. We have combined a mouse model of acute cholestatic liver injury, partial bile duct ligation (pBDL), with a novel longitudinal bioimaging methodology to quantify transcription factor activity during hepatic injury and repair. We administered lentiviral transcription factor activated luciferase/eGFP reporter (TFAR) cassettes to neonatal mice enabling longitudinal TFAR profiling by continued bioimaging throughout the lives of the animals and following pBDL in adulthood. Neonatal intravascular injection of VSV-G pseudotyped lentivirus resulted in almost exclusive transduction of hepatocytes allowing analysis of hepatocyte-specific transcription factor activity. We recorded acute but transient responses with NF-? B and Smad2/3 TFAR whilst our Notch reporter was repressed over the 40 days of evaluation post-pBDL. The bipotent hepatic progenitor cell line, HepaRG, can be directed to differentiate into hepatocytes and biliary epithelia. We found that forced expression of the Notch inhibitor NUMB in HepaRG resulted in enhanced hepatocyte differentiation and proliferation whereas over-expressing the Notch agonist JAG1 resulted in biliary epithelial differentiation. In conclusion, our data demonstrates that hepatocytes rapidly upregulate NF-? B and Smad2/3 activity, whilst repressing Notch signalling. This transcriptional response to cholestatic liver injury likely promotes partial de-differentiation to allow pro-regenerative proliferation of hepatocytes