Resource stoichiometry shapes community invasion resistance via productivity-mediated species identity effects

The diversity-invasion resistance relationships are often variable and sensitive to environmental conditions such as resource availability. Resource stoichiometry, the relative concentration of different elements in the environment, has been shown to have strong effects on the physiology and interactions between different species. Yet, its role for diversity-invasion resistance relationships is still poorly understood. Here we explored how the ratio of nitrogen and phosphorus affect the productivity and invasion resistance of constructed microbial communities by plant pathogenic bacterium, Ralstonia solanacearum. We found that resource stoichiometry and species identity effects affected the invasion resistance of communities. Both high nitrogen concentration and resident community diversity constrained invasions, and two resident species, in particular, had strong negative effects on the relative density of the invader and the resident community productivity. While resource stoichiometry did not affect the mean productivity of the resident community, it favored the growth of two species that strongly constrained invasions turning the slope of productivity-invasion resistance relationship more negative. Together our findings suggest that alterations in resource stoichiometry can change the community resistance to invasions by having disproportionate effects on species growth 37 potentially explaining changes in microbial community composition under 38 eutrophication

Power consideration and caveats of Causal Inference Test (CIT) for mediation analysis

Thesis (Master's)--University of Washington, 2021Causal Inference Test (CIT) has been proposed to infer the causality mediation from a genotype to a trait through a candidate mediator, for example certain gene expression. This thesis aims to study the performance of CIT under diverse settings including partial mediation where the temporal order of the candidate mediator and the trait cannot be determined. Through algebraic derivation and simulation, I show that there are scenarios of partial mediation that CIT will yield false negative results even for a large sample size, and a scenario where CIT will lead to false positives. In conclusion, CIT may not reliably detect the direction of the mediation

Application of Geodesign Techniques for Ecological Engineered Landscaping of Urban River Wetlands: A Case Study of Yuhangtang River

Although geodesign techniques have been studied and developed worldwide, there is still a lack of in-depth application of geodesign workflows for redesigning urban river wetlands with characteristics of ecologically engineered landscaping (EEL). The study mainly aims at putting forward a proper approach in the methodological foundation for EEL practices in river wetlands. A typical EEL-oriented project of river restoration in Hangzhou, China, was conducted in this study. Based on in-situ geodata and tools within QGIS, individual geological factors analysis, with the hierarchical analysis method (AHP) and ecological vulnerability evaluation (EVE), was conducted by experts’ voting and the weighted linear combination (WLC) method. Analysis of hydrological-related factors proceeded. This GIS-based analysis with expert knowledge provided comprehensive redesign solutions for the redesign project, i.e., restoration of the riverbed, spatial restoration in the horizontal and vertical dimensions, and integration with the multifunctional design. Detailed three-dimensional models for design practices were developed to present redesigned topology and space accordingly. Terrain, inundation, and visibility analysis proceeded with parametric mapping programs within Grasshopper to check the feasibility. The adapted geodesign-based workflow in the study also applies to the site analysis, sustainable assessment and landscape planning for urban wetlands EEL projects

Application of Geodesign Techniques for Ecological Engineered Landscaping of Urban River Wetlands: A Case Study of Yuhangtang River

Although geodesign techniques have been studied and developed worldwide, there is still a lack of in-depth application of geodesign workflows for redesigning urban river wetlands with characteristics of ecologically engineered landscaping (EEL). The study mainly aims at putting forward a proper approach in the methodological foundation for EEL practices in river wetlands. A typical EEL-oriented project of river restoration in Hangzhou, China, was conducted in this study. Based on in-situ geodata and tools within QGIS, individual geological factors analysis, with the hierarchical analysis method (AHP) and ecological vulnerability evaluation (EVE), was conducted by experts’ voting and the weighted linear combination (WLC) method. Analysis of hydrological-related factors proceeded. This GIS-based analysis with expert knowledge provided comprehensive redesign solutions for the redesign project, i.e., restoration of the riverbed, spatial restoration in the horizontal and vertical dimensions, and integration with the multifunctional design. Detailed three-dimensional models for design practices were developed to present redesigned topology and space accordingly. Terrain, inundation, and visibility analysis proceeded with parametric mapping programs within Grasshopper to check the feasibility. The adapted geodesign-based workflow in the study also applies to the site analysis, sustainable assessment and landscape planning for urban wetlands EEL projects

Chemical structure predicts the effect of plant-derived low molecular weight compounds on soil microbiome structure and pathogen suppression

Plant-derived low-molecular weight compounds play a crucial role in shaping soil microbiome functionality. While various compounds have been demonstrated to affect soil microbes, most data are case-specific and do not provide generalizable predictions on their effects. Here we show that the chemical structural affiliation of low-molecular weight compounds typically secreted by plant roots—sugars, amino acids, organic acids and phenolic acids—can predictably affect microbiome diversity, composition and functioning in terms of plant disease suppression. We amended soil with single or mixtures of representative compounds, mimicking carbon deposition by plants. We then assessed how different classes of compounds, or their combinations, affected microbiome composition and the protection of tomato plants from the soil-borne Ralstonia solanacearum bacterial pathogen. We found that chemical class predicted well the changes in microbiome composition and diversity. Organic and amino acids generally decreased the microbiome diversity compared to sugars and phenolic acids. These changes were also linked to disease incidence, with amino acids and nitrogen-containing compound mixtures inducing more severe disease symptoms connected with a reduction in bacterial community diversity. Together, our results demonstrate that low-molecular weight compounds can predictably steer rhizosphere microbiome functioning providing guidelines to engineer microbiomes based on root exudation patterns by specific plant cultivars or crop regimes. A free plain language summary can be found within the Supporting Information of this article

CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression

Abstract Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling

Abstract 2149: West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer

Abstract Introduction: Men of West African (WA) ancestry are at higher risk for prostate cancer than men of European (EU) or Asian descent. Caribbean populations provide an opportunity to identify potential founder mutations that contribute to cancer risk. Jamaica has among the highest rates of prostate cancer incidence and mortality in the world and the majority of the population are of WA ancestry. However, there is a significant amount of genetic admixture of EU and Asian ancestry from historic migration patterns. Thus, the population provides a unique cohort for studying the complex interplay between genetic ancestry and prostate cancer. In this pilot study, we characterized the overall and gene locus-specific ancestry of Jamaican prostate cancer patients to explore potential associations with clinicopathologic disease features. We specifically focused this analysis on the BRCA1 locus based on its known association with inherited prostate cancer risk and also with breast cancer risk in patients from the Caribbean. Methods: A retrospective cohort of 31 Jamaican men (non-US citizens/residents) who travelled to the University of Miami (2015-2020) specifically for robotic prostatectomy were included in the analysis. DNA was prepared from normal prostate tissue and analyzed using the Illumina Global Screening Array version 3 with Multi-Disease Drop-In that includes more than 650,000 genetic markers. Both overall genetic ancestry and allele specific ancestries were determined for each study subject. Clinical and pathological features (age, PSA, stage, grade group (GG)) were also recorded and analyzed using descriptive statistics. Results: Median age was 67 years, median pre-op PSA was 6.7. The majority of patients were cT1c (91%) and GG 2 (29%) on biopsy. On final pathology most men were ≥pT3 (51%) and the proportion of GG 1, 2 and ≥ 3 was 3%, 52% and 45% respectively. The mean overall West African genetic ancestry was 51.2% (SD 28.4%). Overall % West African ancestry was not associated with pathological GG. In contrast, 50% of the men who were homozygous for African ancestry alleles at the BRCA1 locus had high-grade prostate cancer (GG 3, 4, 5) versus 37% of the men with non-African or heterozygous BRCA1 genotypes. Conclusions: In a select cohort of Jamaican men, we found that half of patients with BRCA1 alleles derived from West African ancestry also have high grade prostate cancer. BRCA1 of African ancestral origin may contribute to the relatively high prevalence of aggressive prostate cancer in men from Jamaica. Work in progress focuses on an expanded study of associations between allele-specific genetic ancestry and prostate cancer in high-risk populations. Citation Format: Sandra M. Gaston, Anthony J. Griswold, Oleksandr N. Kryvenko, Tianjie Gu, Guan-Nan Zhang, Nachiketh S. Prakash, Yuval Avda, Tarek Ajami, Chad R. Ritch. West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2149

Ancestry‐Specific eQTL Associations in AA/NHW Alzheimer Disease Cohorts

Background Although the genetic etiology of Alzheimer’s Disease (AD) has been shown to vary among ancestrally diverse populations, the influence of genetic variation on the transcriptome within these populations has not yet been extensively investigated. Multi‐ancestry AD datasets featuring both genetic information and gene expression measurements are needed to support expression quantitative trait loci (eQTl) studies in historically underrepresented populations. In this work, we have compared eQTL signals in case/control AD sample populations of both African American (AA) and non‐Hispanic white (NHW) ancestries. Method We analyzed cohorts of AA and NHW ancestries (Naa = 232, Nnhw = 241) with corresponding array‐based genotypes and RNA‐seq mRNA expression levels from whole blood, along with clinical AD diagnoses (Naa_case = 115, Naa_control = 117, Nnhw_case = 121, Nnhw_control = 120). Transcriptome‐wide eQTL associations between genetic variants and gene expression levels were assessed via regression across 17,638 gene units, adjusting for age, sex, experimental factors, and genetic principal components. This was repeated across all sample set combinations of ancestry‐AD pairings (ancestry = [aa, nhw, both] * AD = [case, control, both]). Result The number of significant (p‐value < 10e‐7) eQTL signals varied by ancestry, with the AA cohort showing 76,742 raw eQTL associations, the NHW cohort 19,734, and both ancestries combined 81,763. When further sub‐setting sample sets to AD cases only, 770 and 788 significant eQTL signals were observed for AA and NHW cohorts respectively, which impacted 135 (AA) and 130 (NHW) genes. Interestingly, these ancestry‐aware, case‐only eQTLs were remarkably distinct between the two ancestries, with only 71 (∼9.1%) of the eQTLs and only 19 (∼14.3%) of the impacted genes being shared by both ancestral cohorts. Of particular interest is the appearance of WWOX (a gene of wide neurological importance, and known AD risk loci), as differentially significant in the AA cohort (P = 8.07e‐7) as compared to the NHW cohort (P = 9.06e‐3). Conclusion We have observed differences in eQTL signals relative to AD diagnosis status between AA and NHW sample populations, which may indicate the presence of novel ancestry‐specific effects impacting the genetic etiology of AD through changes in gene expression