Biology subjects

Byron, M.

Publications and source records attributed to Byron, M..

4 recordsLinked to original sources

bioRxiv2026

Neuroepithelial reprogramming and ERBB vulnerability in canine acanthomatous ameloblastoma

Canine acanthomatous ameloblastoma (CAA) is a locally invasive benign oral neoplasm that is difficult to distinguish from canine oral squamous cell carcinoma (COSCC) due to overlapping clinical, radiologic, and histologic features. Although both tumors exhibit MAPK pathway activation, their mutational landscapes are distinct. Furthermore, previous studies using bulk RNA sequencing (RNA-seq) have demonstrated pronounced differences in programs related to, among others, hypoxia, PI3K-AKT signaling, and cell proliferation. However, these bulk studies lacked the resolution to elucidate the cellular heterogeneity of CAA relative to COSCC. We therefore performed single-nucleus RNA-seq to define the cellular gene expression landscape of CAA, COSCC, and healthy gingiva. Across [~]205,000 nuclei, we identified major epithelial, immune, endothelial, and mesenchymal populations, as well as two epithelial subtypes uniquely enriched in CAA. The CAA-specific keratinocytes exhibited a neuronal-like expression program defined by synaptic regulators, KRAS-associated signaling pathways, and markedly elevated expression of PEG3, ERBB4, GABRB1, MAGI2, and CASK. These findings were validated by bulk RNA-seq, qPCR, and immunohistochemistry, which demonstrated strong nuclear localization of PEG3 exclusively in CAA epithelium. A kinase inhibitor screen independently identified ERBB4 as a candidate therapeutic vulnerability, and pharmacologic inhibition with neratinib was effective. Together, these findings reveal a previously unrecognized neuroepithelial cell state that defines CAA, distinguishes it from COSCC, and reveals unique diagnostic and therapeutic signaling dependencies. Given the molecular and histopathologic parallels between CAA and human ameloblastoma, these data further position CAA as a naturally occurring comparative model for studying ameloblastoma biology and therapeutic vulnerabilities. Significance StatementCanine acanthomatous ameloblastoma (CAA) is a common locally aggressive oral neoplasm often misdiagnosed as canine oral squamous cell carcinoma (COSCC) due to overlapping clinical, radiologic, and histologic features. Using single-nucleus RNA sequencing of CAA, COSCC, and healthy gingiva, we resolve the microenvironment of these tumors and detect two epithelial subpopulations unique to CAA. These CAA-specific keratinocytes exhibit a neuroepithelial-like signature characterized by synaptic regulators, KRAS-associated signaling, and elevated PEG3 and ERBB4 expression. Functional kinase inhibitor screening of patient derived microtumor slices independently converged on ERBB4 as an effective therapeutic target. Together, our study provides a molecular framework for distinguishing CAA from COSCC and establishes a comparative oncology model with translational relevance to human ameloblastoma and other ERBB-driven epithelial neoplasms.

cancer biology↗

bioRxiv2023

Metachronal coordination enables omnidirectional swimming via spatially distributed propulsion

Aquatic organisms often employ maneuverable and agile swimming behavior to escape from predators, find prey, or navigate through complex environments. Many of these organisms use metachronally coordinated appendages to execute complex maneuvers. However, though metachrony is used across body sizes ranging from microns to tens of centimeters, it is understudied compared to the swimming of fish, cetaceans, and other groups. In particular, metachronal coordination and control of multiple appendages for three-dimensional maneuvering is not fully understood. To explore the maneuvering capabilities of metachronal swimming, we combine 3D high-speed videography of freely swimming ctenophores (Bolinopsis vitrea) with reduced-order mathematical modeling. Experimental results show that ctenophores can quickly reorient, and perform tight turns while maintaining forward swimming speeds close to 70% of their observed maximum -- performance comparable to or exceeding that of many vertebrates with more complex locomotor systems. We use a reduced-order model to investigate turning performance across a range of beat frequencies and appendage control strategies, and reveal that ctenophores are capable of near-omnidirectional turning. Based on both recorded and modeled swimming trajectories, we conclude that the ctenophore body plan enables a high degree of maneuverability and agility, and may be a useful starting point for future bioinspired aquatic vehicles. Author summaryMetachronal swimming--the sequential, coordinated beating of appendages arranged in a row-- exists across a wide range of sizes, from unicellular organisms (micrometers) to marine crustaceans (tens of centimeters). While metachronal swimming is known to be scalable and efficient, the level of maneuverability and agility afforded by this strategy is not well understood. This study explores the remarkable 3D maneuverability of ctenophores (comb jellies), and the appendage control strategies they use to achieve it. Ctenophores have eight rows of appendages (instead of the one or two found in crustaceans and other organisms). This higher number of appendages, their distribution along the body, and the independent frequency control between paired rows enables near-omnidirectional swimming and turning performance, placing ctenophores among the most maneuverable swimmers. We use experiments and mathematical modeling to explore both the real and theoretical performance landscape of the ctenophore body plan, and show that ctenophores are capable of executing tight turns at high speeds in nearly any plane. This omnidirectional swimming capability gives insight into the ecology and behavior of an important taxonomic group, and shows the potential of metachronal swimming as a source of design inspiration for robotic vehicles (particularly those that must navigate complex environments).

animal behavior and cognition↗

bioRxiv2022

Human XIST RNA acts early to condense architecture which facilitates A-repeat density-dependent initiation of gene silencing

XIST RNA triggers gene silencing chromosome-wide and transforms a euchromatic chromosome into a condensed Barr body. XIST is heavily studied in mouse ES cells, but here an inducible iPSC system allows analysis of initial steps in human chromosome silencing, revealing key points not known in either system. XIST RNA distribution was examined relative to biochemical and transcriptional changes directly within architecture of individual chromosome territories. Within a few hours of induction, XIST transcripts distribute as a large "sparse zone" and a smaller "dense zone", which, importantly, exhibit different effects on chromatin. Very sparse transcripts immediately trigger bright staining for H2AK119ub and CIZ1, a structural matrix protein. In contrast, H3K27me3 enrichment comes hours later and is much more restricted to the smaller dense RNA zone, which enlarges as the chromosome condenses. Importantly, silencing of several genes examined occurred well after architectural condensation, suggesting a possibly separable step. Surprisingly, we show the small A-repeat fragment of XIST can alone silence endogenous genes; however, results indicate this requires high local RNA density for effective histone deacetylation. Results support a concept whereby XIST RNA acts directly to condense the chromosome territory, comprised largely of non-coding DNA, which facilitates a required step to initiate gene silencing by the A-repeat. Hence, compacted architecture is not a consequence of collective gene silencing, but an early step required for chromosome-wide gene silencing.

cell biology↗

bioRxiv2019

Short-term effects of GPS collars on the activity, behavior, and adrenal response of scimitar-horned oryx (Oryx dammah)

GPS collars have revolutionized the field of animal ecology, providing detailed information on animal movement and the habitats necessary for species survival. GPS collars also have the potential to cause adverse effects ranging from mild irritation to severe tissue damage, reduced fitness, and death. The impact of GPS collars on the behavior, stress, or activity, however, have rarely been tested on study species prior to release. The objective of our study was to provide a comprehensive assessment of the short-term effects of GPS collars fitted on scimitar-horned oryx (Oryx dammah), an extinct-in-the-wild antelope once widely distributed across Sahelian grasslands in North Africa. We conducted behavioral observations, assessed fecal glucocorticoid metabolites (FGM), and evaluated high-resolution data from tri-axial accelerometers. Using a series of non-standard regression models, we illustrate clear but short-term effects to animals fitted with GPS collars. Behavioral observations highlighted a significant increase in the amount of headshaking from pre-treatment levels, returning below baseline levels during the post-treatment period (>3 days post-collaring). Similarly, FGM concentrations (i.e., stress hormones) increased after GPS collars were fitted on animals but returned to pre-collaring levels within 5 days of collaring. Lastly, tri-axial accelerometers, collecting data at eight positions per second, indicated a > 480 percent increase in the amount of hourly headshaking immediately after collaring. This post-collaring increase in headshaking was estimated to decline in magnitude within 4 hours after GPS collar fitting. These effects constitute a handling and/or habituation response (model dependent), with animals showing short-term responses in activity, behavior, and stress that dissipated within several hours to several days of being fitted with GPS collars. Importantly, none of our analyses indicated any long-term effects that would have more pressing animal welfare concerns.

ecology↗