Biology subjects

Edwards, C. E.

Publications and source records attributed to Edwards, C. E..

12 recordsLinked to original sources

bioRxiv2026

Genomic Consequences of Altered Flood Regimes: Gene Flow and Adaptation in a Threatened Floodplain Plant

Floodplains are highly dynamic ecotones where species persistence depends on synchrony between natural flow regimes and life-history. Artificial river engineering has profoundly altered these systems by reducing the frequency and magnitude of spring floods while increasing the unpredictability of flood timing and intensity during summer. These hydrological changes have disrupted historical patterns of dispersal, growth, reproduction, and competitive success among floodplain specialists. Effective conservation in these ecosystems therefore requires understanding how human-altered flow regimes have reshaped floodplain specialists' demography, genetic diversity, genetic connectivity, functional variation, and adaptive potential. Here, we address this challenge in Boltonia decurrens, a federally threatened floodplain plant endemic to the Illinois River Valley, by integrating a chromosome-scale reference genome, whole-genome resequencing, and common-garden adaptive trait measurements from 424 individuals across 17 populations. Demographic analyses revealed a severe recent bottleneck and a subsequent rebound. Population structure was clinal with downstream-dominant gene flow, indicating that regional population connectivity predominates over longer-distance gene flow. A subset of populations showed elevated genetic isolation with increased inbreeding and homozygous deleterious burden, revealing a genomic cost of disrupted floodplain connectivity. Common-garden observations and GWAS showed extensive within-population phenotypic and genetic variation in flowering time, flowering stem height, and year of first flowering (1st vs. 2nd year), which are hypothesized to buffer populations and to be selectively maintained under human-altered flow regimes. Finally, landscape-genomic approaches detected a divergent haplotype block separating northern and southern populations, suggesting that adaptive divergence can persist even in a system shaped by recurrent disturbance and ongoing gene flow.

evolutionary biology↗

bioRxiv2026

A disjunct distribution and population fragmentation shape rangewide genetic diversity and structure of the endangered Physaria globosa (Brassicaceae)

Population genetic analysis of species of conservation concern provides information to devise management plans to effectively conserve the genetic variation of endangered species. One such endangered plant, Physaria globosa is a federally endangered species in the mustard family with a geographically restricted range that occurs in four disjunct locations in Indiana, Kentucky, and Tennessee (i.e., Highland Rim and Nashville Basin regions) and along the Wabash, Kentucky, and Cumberland Rivers. In this study, we sampled populations from throughout the range of P. globosa, genotyped them using 20 microsatellite loci, and assessed genetic diversity and structure within and among populations. The goals of the study were to understand: 1) levels of genetic diversity in P. globosa and whether populations show evidence of having experienced reductions in genetic diversity as the result of genetic bottlenecks, genetic drift, or inbreeding, 2) rangewide genetic diversity and structure in P. globosa and how genetic structure is affected by the disjunctions in the species range, and 3) implications for prioritization of in-situ and ex-situ conservation efforts. On average, P. globosa showed comparable levels of genetic diversity to other species of Physaria. However, some populations showed evidence of inbreeding, genetic bottlenecks, or decreases in genetic diversity, possibly due to anthropogenic or climate-related pressures and decreases in population size due to competition with invasive bush honeysuckle. Genetic variation was strongly structured into two main geographic groups, one in the northern part of the species range (KY and IN), and the other in the southern part of the species range (TN), but some populations likely originated via long-distance dispersal. We also found significant isolation by distance, likely due to both life history characteristics and physical barriers associated with the complex topological structure of the landscape occupied by P. globosa, limiting population connectivity. Given the strong genetic structure found in P. globosa, several populations should be protected and managed within each geographic region to conserve genetic variation. Ex situ conservation will also be important to protect genetic diversity, particularly for populations that are difficult to access and manage.

genetics↗

bioRxiv2025

Airway Epithelial SARS-CoV-2 Infectious and Repair Responses: Relationships to Age, Sex, and Post-COVID Pulmonary Syndromes

The long-term pulmonary sequelae of SARS-CoV-2 respiratory infections reflect infection severity, innate and adaptive immunity, and respiratory epithelial repair. This study investigated the acute and reparative responses as a function of age and sex in primary human bronchial epithelial (HBE) cultures utilizing a 14-day SARS-CoV-2 infection protocol. SARS-CoV-2 infection peaked at 3 days post-infection (dpi) with an [~] 2 log titer suppression at 14 dpi. SARS-CoV-2 infection induced interferon, interferon-induced gene, and cell damage responses. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. Repair processes were infection severity-dependent, not sex-dependent, and were more robust in young donor cultures. Analyses of long-COVID subjects with persistent pulmonary fibrosis or persistent bronchitic airway diseases exhibited expression of HBE 14 dpi failed repair gene signatures, including ISG gene signatures. Human airway epithelial repair post-SARS-CoV-2 is prolonged and incomplete in vitro over 14 days, and persistently abnormal repair may contribute to phenotypes of people with long-COVID pulmonary syndrome.

cell biology↗

bioRxiv2025

Mouse Adapted Omicron BA.5 Induces A Fibrotic Lung Disease Phenotype in BALB/c Mice

Following SARS-CoV-2 Omicron BA.1, subsequent Omicron sub-lineages have continued to emerge, challenging the development of intervention and prevention strategies, including monoclonal antibodies and vaccines. To better understand the pathogenic effects caused by Omicron BA.5 infection, we developed a mouse-adapted virus with overt disease burden in BALB/c mice. Acute disease was characterized by significant weight loss and lung dysfunction following high-dose challenges. In survivor animals that were followed through 107 days post-infection, subpleural fibrosis with associated tertiary lymphoid structures was noted. Serum from these mice demonstrated potent neutralization against BA.5, with substantially reduced neutralization titers against early epidemic, zoonotic, and more recent contemporary XBB.1.5 variants. Intervention with pre-clinical monoclonal antibodies revealed that robust protection from BA.5-induced lung disease was possible after prophylactic administration. Together, this model enables the investigation of therapeutic approaches for both acute and post-acute sequelae of COVID-19. ImportanceIn order to best combat the evolving landscape of SARS-CoV-2 variants of interest and variants of concern the development of effective small animal models is of critical importance. Herein, we describe the development of a model system in BALB/c mice to study the effects of SARS-CoV-2 BA.5 in both acute and chronic disease manifestations. Intriguingly, we determined that fibrotic lung disease with tertiary lymphoid structures was a prominent feature in the lungs of mice that survived through the acute phase of infection. This is a prominent concern in human patients that survive the initial infection insult. As such, and most critically, the model system presented here provides researchers with an effective pathway in which long COVID manifestations and potential interventions can be studied.

molecular biology↗

bioRxiv2025

Digging into the general dynamic model: Island ontogeny predicts shifting micro-evolutionary processes in a Mascarene flowering plant radiation

AO_SCPLOWBSTRACTC_SCPLOWIsland studies have been integral in the development of process-oriented biodiversity models such as the general dynamic model (GDM) of oceanic island biogeography. While empirical tests of the GDM primarily come from phylogeographic studies, tests incorporating comprehensive population-level sampling of island radiations are rare. In this study, we elucidate the evolutionary processes driving the diversification of Hibiscus section Lilibiscus in the Mascarene archipelago using population-level sampling and 2bRAD sequencing. Our goals were to: 1) assess species relationships and resolve taxonomic issues; 2) test patterns of intra- and interspecific genetic differentiation under a model of shifting speciation processes as islands age; and 3) utilize demographic modeling to infer the relative divergence times of populations in the archipelago. We found the Mascarene radiation of sect. Lilibiscus to be monophyletic and confirmed the presence of six morphologically distinct species. Species richness and phylogenetic relationships supported the expectations of the GDM. Namely, we found that morphologically similar populations of the same species on the intermediate-aged island, Mauritius, diverged earlier and showed greater divergence than morphologically disparate species on the youngest Mascarene island, Reunion. These patterns are consistent with the hypothesis that ecological selection may be affecting speciation on the youngest island, drift may be the most important force on the middle-aged island. Although not tested here, given that the oldest island is in a late stage of subsidence, extinction may be the most important evolution force occurring on the oldest island, consistent with the expectation that evolutionary processes occurring across each of these islands may be influenced by ontogenetic stage. We also found evidence that some species in the group may be naturally rare, suggesting that the rarity of species may not only be from recent habitat loss. Our study is the first to use population-level data to test complex predictions of the GDM and demonstrate that the most important evolutionary processes shift depending on island ontogeny.

evolutionary biology↗

bioRxiv2021

Thiol-based mucolytics exhibit antiviral activity against SARS-CoV-2 through allosteric disulfide disruption in the spike glycoprotein

Small molecule therapeutics targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lagged far behind the development of vaccines in the fight to control the COVID-19 pandemic. Here, we show that thiol-based mucolytic agents, P2119 and P2165, potently inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine profiling link the antiviral activity of repurposed mucolytic agents to the reduction of key disulfides, specifically, by disruption of the Cys379-Cys432 and Cys391-Cys525 pairs distal to the receptor binding motif (RBM) in the receptor binding domain (RBD) of the spike glycoprotein. Computational analyses provide insight into conformation changes that occur when these disulfides break or form, consistent with an allosteric role, and indicate that P2119/P2165 target a conserved hydrophobic binding pocket in the RBD with the benzyl thiol warhead pointed directly towards Cys432. These collective findings establish the vulnerability of human coronaviruses to repurposed thiol-based mucolytics and lay the groundwork for developing these compounds as a potential treatment, preventative and/or adjuvant against infection.

microbiology↗

bioRxiv2020

The evolutionary assembly of forest communities along environmental gradients: recent diversification or sorting of pre-adapted clades?

O_LIBiogeographic events occurring in the deep past can contribute to the structure of modern ecological communities. However, little is known about how the emergence of environmental gradients shape the evolution of species that underlie community assembly. In this study, we address how the creation of novel environments lead to community assembly via two non-mutually exclusive processes: 1) the immigration and ecological sorting of pre-adapted clades (ISPC), and 2) recent adaptive diversification (RAD). We study these processes in the context of the elevational gradient created by the uplift of the Central Andes. C_LIO_LIWe develop a novel approach and method based on the decomposition of species turnover into within- and among-clade components, where clades correspond to lineages that originated before mountain uplift. Effects of ISPC and RAD can be inferred from how components of turnover change with elevation. We test our approach using data from over 500 Andean forest plots. C_LIO_LIWe found that species turnover between communities at different elevations is dominated by the replacement of clades that originated before the uplift of the Central Andes. C_LIO_LIOur results suggest that immigration and sorting of clades pre-adapted to montane habitats is the primary mechanism shaping communities across elevations. C_LI

ecology↗

bioRxiv2020

Understanding how an amphicarpic species with a mixed mating system responds to fire: a population genetic approach

Amphicarphic species produce both aboveground and belowground seeds; the belowground seeds have been proposed to be an adaptation to disturbed sites because they are protected belowground, enabling them to persist and recolonize a site after disturbance. However, it is unknown whether such seeds indeed serve as the main colonizers after a disturbance. The amphicarpic species Polygala lewtonii is endemic to fire-prone Florida sandhill and scrub and is among only a few species with three flower types (aboveground chasmogamous flowers and both above and belowground cleistogamous flowers). The goal of this study was to understand whether recolonization of sites by P. lewtonii was accomplished primarily through germination of belowground seed. First, we quantified the outcrossing rate in seeds produced by aboveground chasmogamous flowers to determine whether we could detect differences in colonization of between seeds produced aboveground vs. belowground. Approximately 25% of seeds from aboveground chasmogamous flowers showed evidence of cross pollination and the seeds showed greater heterozygosity and lower inbreeding coefficients than pure selfing, indicating that it is possible to differentiate between selfed and non-selfed seed types in postfire colonization. Second, we analyzed genetic diversity, inbreeding, and genetic structure of the populations before and after a prescribed fire. If heterozygosity and admixture increased, and spatial population genetic structure and inbreeding decreased, this would indicate that fire promoted germination of outcrossed seed from aboveground flowers. However, inbreeding increased and spatial genetic structure and admixture decreased after fire, suggesting that selfed seed produced by belowground flowers predominantly recolonized the site after fire. Thus, amphicarpy is a powerful adaptation to fire-maintained environments by producing seeds that are well suited to the range of conditions presented by a highly variable, disturbance prone habitat.

plant biology↗

bioRxiv2020

SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo

The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.

microbiology↗

bioRxiv2020

Epigenomic patterns reflect irrigation and grafting in the grapevine clone 'Chambourcin'

Although DNA methylation has largely been shown to be stable in plants, mounting evidence indicates methylation patterns may reflect environmental sensitivity. Perennial plants experience seasonal and inter-annual environmental variation, and clonal replicates of some long-lived plants, including many perennial crops, survive in a broad range of environments. This makes perennial crops a compelling study system to investigate links between the plant epigenome and environmental variation. In this study, we used whole genome bisulfite sequencing and small RNA sequencing to characterize the epigenome in 12 clonal replicates of the winegrape cultivar Chambourcin. We asked whether DNA methylation varied in response to a full factorial combination of irrigation and grafting treatments. We found signatures of both irrigation and grafting in the Chambourcin epigenome, as well as compelling evidence for a unique interaction effect whereby grafting appeared to override or mitigate epigenomic changes associated with irrigation in ungrafted vines. These findings indicate that the epigenome responds to environmental and agronomic manipulations, suggesting the epigenome might be a mechanism underlying how long-lived, clonal plants respond at the molecular level to their environment. Further research is needed to assess the potential relevance of variation in DNA methylation to plant form and function, and to address the implications of environmentally-inducible patterns of DNA methylation on the adaptive capacity of long-lived woody perennials in nature and under cultivation.

genomics↗

bioRxiv2020

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 "apical-out" organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

cell biology↗

bioRxiv2020

A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures

Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections.

microbiology↗