Biology subjects

Porter, S.

Publications and source records attributed to Porter, S..

8 recordsLinked to original sources

bioRxiv2026

Selection For Yield Enhanced Rhizobial Mutualism In Pea

Crop improvement can enhance food security, but side effects, such as trade-offs between valuable agronomic traits, are common. Likewise, fertilisation helps ensure high yields, but can devalue mutualisms with soil microbes that would otherwise be essential for nutrient acquisition. If the need for nutritional mutualisms is reduced in crops, mutualisms could be disrupted by selection relaxation or allocation trade-offs. Thus, crops could achieve high yields in spite of, or because of, disruption of nutritional mutualisms. Alternatively, the highest-yielding plants might flourish because they maximise nutrient acquisition from both symbionts and the soil. Here, enhanced mutualism could evolve over the course of agricultural crop improvement. To investigate whether high yields in cultivars and wild accessions are negatively or positively genetically correlated with outcomes in the legume-rhizobia mutualism, we measured whether yield and symbiosis traits trade-off or are positively genetically correlated among cultivars and wild accessions. We also tested whether this relationship differs between accessions released before or after 1950. We measured genetic correlations between yield and mutualism traits in 87 domesticated pea (Pisum sativum) accessions in a common garden agricultural field across three years. Seed yield and N2 fixation (%Ndfa) were positively genetically correlated. While N fixation was more strongly predictive of yield in the pre-1950 accessions than the post-1950 accessions, the underlying positive genetic correlation between the traits did not differ between the groups. The positive genetic correlation between yield and N2 fixation indicates that selection to increase yields has maintained or increased the benefits of the rhizobial mutualism in pea. Our findings predict that breeding to increase yield may continue to produce pea cultivars that get a greater proportion of their N from rhizobia, enhancing symbiotic mutualism and reducing the proportion of N supplied by fertilisation.

plant biology↗

bioRxiv2026

The stem cell compartment in human oral mucosa and its activation in oral lichen planus.

In mice, oral epithelial stem cells (OESCs) are essential for oral mucosal homeostasis and repair. Less is known regarding the role of OESCs in the human oral mucosa. Here, we studied the behaviour of OESCs and their contribution to tissue maintenance and repair in oral lichen planus (OLP). OLP is a chronic T cell-mediated disease characterized by basal keratinocyte degeneration, epithelial atrophy, acanthosis, and hyperkeratosis. Using immunohistological techniques and semi-automated image analysis, we observed that in OLP proliferative activity was increased in the normally largely quiescent basal cell compartment. In areas of OLP mucosa with intact basal cell layer, expression of NGFR, KRT15, and KRT19-markers of slowly cycling reserve OESCs, was strongly reduced or absent. In contrast, expression of CSPG4, a marker for actively cycling stem cells, was increased in OLP basal cells. Tissue compartmentalization, as evaluated by keratin expression, was strongly disturbed. Taken together, our findings indicate that the inflammation in OLP leads to activation and proliferation of OESCs that give rise to a population of cells with an aberrant differentiation programme. Along with the well-documented epithelial up-regulation of anti-apoptotic proteins in OLP, this likely reflects an attempt by the epithelium to avoid overt ulceration.

cell biology↗

bioRxiv2026

Deletion of Dock7 Exons 3 and 4 Results in Reduced Trabecular Microarchitecture and a Decrease in Mineralization

Dedicator of Cytokinesis 7 (DOCK7) has recently emerged as a regulator of skeletal homeostasis, but existing Dock7 mutant models harbor only global mutations and are incompatible with tissue-specific deletion studies. We previously generated a Dock7-floxed allele in which exons 3-4 are flanked by LoxP sites. To validate the utility of this allele for future conditional strategies, we globally deleted exons 3-4 to generate Dock7em2/em2 mice and characterized their skeletal phenotype. Homozygous Dock7em2/em2 mice exhibited a diluted coat color and white belly spot, consistent with spontaneous Dock7 mutations, whereas heterozygotes exhibited no spotting or coat changes. Bone microarchitecture was assessed in 21-week-old males and females. Global deletion of Dock7 exons 3-4 resulted in a 30-37% reduction in trabecular bone volume in the distal femur and L5 vertebrae. Cortical bone thickness was unchanged, though sex-specific alterations in femoral area suggested altered appositional bone growth. Mass spectrometry (SWATH) analysis of Dock7em2/em2 bone marrow stromal cells (BMSCs) identified DOCK7 protein levels similar to control mice, likely resulting from an alternative translational start site. Despite stable protein abundance prior to differentiation, BMSCs from Dock7em2/em2 mice exhibited reduced mineralization and decreased Bglap expression, indicating attenuated osteoblast differentiation. These findings demonstrate that Dock7 exons 3-4 are required for normal trabecular bone acquisition and osteoblast function. While the Dock7-em2 allele likely encodes a truncated protein product, its recapitulation of the Misty skeletal phenotype confirms that exons 3-4 are essential for DOCK7 activity. These studies in the Dock7em2/em2 mouse provide a foundation for future tissue-specific deletion studies utilizing the Dock7 exon 3-4 deletion model to define the cellular roles of DOCK7 in regulating bone formation and trabecular architecture. Lay SummaryIdentifying genes that regulate bone mass is essential for understanding osteoporosis. Mutation of the Dock7 gene in mice results in low bone mass, similar to human osteoporosis. Previous models could not isolate its role in specific tissues, limiting our ability to understand how DOCK7 controls bone mass. We developed a new mouse model where Dock7 can be mutated in specific tissues. In this study, we bred mice to carry this mutation across all tissues, causing significant bone loss. This validates a flexible tool for future research to mutate DOCK7 in specific cell types and map its role in skeletal health.

cell biology↗

bioRxiv2023

High-Content Screening to Identify Inhibitors of Dengue Virus Replication

Dengue Virus (DENV) causes dengue fever, a pandemic-potential disease with currently no FDA-approved antivirals. Additionally, the available vaccine for DENV can increase the risk of severe dengue fever for those who have never had a DENV infection due to antibody-dependent enhancements. Thus, there is an urgent need to identify dengue virus antivirals. Antivirals that target NS4B, the replication compartment forming protein of DENV and the flavivirus family, are a promising new drug class that minimize cytotoxic effects to host cells. Drug-repurposing and high-content screening were leveraged to efficiently identify antivirals likely to inhibit NS4B. Using high-content screening, we quantified the morphological patterns of NS4B and envelope (E) protein expression versus time and developed a viral pseudotime model that was able to predict the infection progression to enable drug screening. We then developed a single cell infection classifier for antiviral efficacy and performed high-throughput drug screening of 960 compounds. We identified four concentration-dependent inhibitors of DENV with nanomolar potencies including: Nexium, Pralatrexate, GW4064, and LY411575. LY411575, a gamma secretase inhibitor, exhibited an IC50 of 72nM and reduced percent infection to levels indistinguishable from the mock infection control.

cell biology↗

bioRxiv2022

One thousand soils for molecular understanding of belowground carbon cycling

While significant progress has been made in understanding global carbon (C) cycling, the mechanisms regulating belowground C fluxes and storage are still uncertain. New molecular technologies have the power to elucidate these processes, yet we have no widespread standardized implementation of molecular techniques. To address this gap, we introduce the Molecular Observation Network (MONet), a decadal vision from the Environmental Molecular Sciences Laboratory (EMSL), to develop a national network for understanding the molecular composition, physical structure, and hydraulic and biological properties of soil and water. These data are essential for advancing the next generation of multiscale Earth systems models. In this paper, we discuss the 1000 Soils Pilot for MONet, including a description of standardized sampling materials and protocols and a use case to highlight the utility of molecular-level and microstructural measurements for assessing the impacts of wildfire on soil. While the 1000 Soils Pilot generated a plethora of data, we focus on assessments of soil organic matter (SOM) chemistry via Fourier-transform ion cyclotron resonance-mass spectrometry and microstructural properties via X-ray Computed Tomography to highlight the effects of recent fire history in forested ecosystems on belowground C cycling. We observed decreases in soil respiration, microbial biomass, and potential enzyme activity in soils with high frequency burns. Additionally, the nominal oxidation state of carbon in SOM increased with burn frequency in surface soils. This results in a quantifiable shift in the molecular signature of SOM and shows that wildfire may result in oxidation of SOM and structural changes to soil pore networks that persist into deeper soils.

ecology↗

bioRxiv2021

Survey of peridomestic mammal susceptibility to SARS-CoV-2 infection

Wild animals have been implicated as the origin of SARS-CoV-2, but it is largely unknown how the virus affects most wildlife species and if wildlife could ultimately serve as a reservoir for maintaining the virus outside the human population. Here we show that several common peridomestic species, including deer mice, bushy-tailed woodrats, and striped skunks, are susceptible to infection and can shed the virus in respiratory secretions. In contrast, we demonstrate that cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and racoons are not susceptible to SARS-CoV-2 infection. Our work expands upon the existing knowledge base of susceptible species and provides evidence that human-wildlife interactions could result in continued transmission of SARS-CoV-2.

microbiology↗

bioRxiv2020

Epigenetic aging of classical monocytes from healthy individuals

The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older individuals (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) - a novel, cell-type specific signature of aging in DNA methylome. Optimized ultra-low-input ChIP-seq (ULI-ChIP-seq) data acquisition and analysis pipelines applied to 5 chromatin marks for each individual revealed lack of large-scale age-associated changes in chromatin modifications and allowed us to link hypo- and hypermethylated DMRs to distinct chromatin modification patterns. Specifically, hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with normal pattern of expression. Furthermore, hypo- and hypermethylated DMRs followed distinct functional and genetic association patterns. Hypomethylation events were associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells. Furthermore, these locations were also enriched in genetic regions associated by GWAS with asthma, total blood protein, hemoglobin levels and MS. On the other side, acceleration of epigenetic age in HIV and asthma stems only from changes in hypermethylated DMRs but not from hypomethylated loci.

systems biology↗

bioRxiv2019

Toxoplasma gondii infection drives conversion of NK Cells into ILC1s

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here we describe Toxoplasma gondii infection converts NK cells into cells resembling steady-state ILC1s that are heterogeneous and distinct from both steady-state NK cells and ILC1s in uninfected mice. Most toxoplasma-induced ILC1s were Eomes-dependent, indicating that NK cells can give rise to Eomes- Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

immunology↗