Biology subjects

Lyons, K.

Publications and source records attributed to Lyons, K..

7 recordsLinked to original sources

bioRxiv2026

Divergence in neurodivergent brains: mapping the relationship between developmental trajectories in functional connectivity and clinical outcomes

Brain network development differs between neurodivergent (ND) and neurotypical (NT) youth, but its developmental trajectory, and relationship to clinical outcomes, remains unclear. We examined age-related changes in functional network connectivity and clinical symptoms in 861 participants (5-21 years) from the Healthy Brain Network, including NT youth and those with Neurodevelopmental Disorders (NDDs) and generalized anxiety disorder (GAD). Functional connectivity during movie-watching was modeled using generalized additive models across eight large-scale networks to characterize nonlinear developmental trajectories. Divergence in connectivity profiles between ND and NT groups first emerged during late childhood and were largest during adolescence. Importantly, divergence in connectivity patterns followed a similar trajectory path, but preceded, divergence in clinical outcomes. These findings identify adolescence as a sensitive period when differences in patterns of brain activity and clinical differences become increasingly pronounced, highlighting a potential window for targeted intervention.

neuroscience↗

bioRxiv2026

Cartilage canals in sharks and rays show that blood vessels can exist in mature cartilage without triggering endochondral bone formation

Although cartilage in tetrapod skeletons is typically said to lack blood vessels, this is only true for adult cartilage. In young bird and mammal cartilage, a dense network of vasculature-containing tunnels --cartilage canals-- perforate the growing skeleton, helping nourish the cartilage and develop the ossification centers that will later form the skeletons epiphyseal bone. As the canals and their rich vascular network typically recede as animals age, the healthy cartilage of adult animals is typically known to be avascular. Here, however, we use a range of tissue characterization and visualization techniques --including light/electron microscopy and microCT-- to show that the skeletons of rays and sharks (elasmobranch fishes) not only possess cartilage canals, but that these structures persist in the adult skeleton. The morphology and tissue composition of elasmobranch cartilage canals argues homology with mammalian cartilage canals and an ancient invasion of the vascular system into cartilage. However, the anatomical location of canals --extending away from mineralized tissue not toward it-- and the lack of endochondral ossification in ray and shark cartilage suggest that cartilage canals developed early in vertebrates as a transport system for nutrients and mesenchymal cells into the growing skeleton. We describe distinctive features and variation in elasmobranch cartilage canals, discuss their possible roles and their potential for tissue mineralization, and the biomedical implications for their presence in a clade of animals with continuously growing cartilaginous skeletons.

evolutionary biology↗

bioRxiv2026

Paralysis Efficiency (ED50) Scales Linearly with Lethality (LD50) in Spider Venoms

Historically, venom potencies have been assessed using measures of lethality, such as the median lethal dose (LD50). However, venoms may be selected primarily for their ability to rapidly incapacitate rather than cause mortality, meaning LD50 may not capture the efficacy of venoms in an ecological and evolutionary context. To capture this context, recent studies have adapted measures that assess venoms ability to rapidly incapacitate, such as the median effective dose (ED50). However, while ED50 values are expected to provide a more proximate assessment of ecological variation in venom potency, it is unknown whether historically available LD50 values are still useful proxies of ecologically relevant potency or whether they capture independent axes of venom variation. Here, we test the relationship between LD50 and ED50 in spider venoms by experimentally estimating LD50 and ED50 for 12 species and collating additional potency data for 40 species retrieved from the literature. We observed an isometric relationship between LD50 and ED50 in both analyses, showing these potency measures are both strongly coupled, with an increase in paralysis efficiency associated with a similar increase in lethality. Our results suggest that the functional aspects of venom potency, paralysis and lethality, are intrinsically linked, and due to this strong mechanistic coupling, historically available LD50 values may be used to compare general venom potencies in spiders, provided that they are based on the same prey model.

pharmacology and toxicology↗

bioRxiv2025

Detection and monitoring of translocation renal cell carcinoma via plasma cell-free epigenomic profiling

TFE3 translocation renal cell carcinoma (tRCC), an aggressive kidney cancer driven by TFE3 gene fusions, is frequently misdiagnosed owing to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays that detect tumor DNA via somatic mutations or copy number alterations are unsuitable for tRCC, since it often lacks recurrent genetic alterations and because fusion breakpoints are highly variable between patients. We reasoned that epigenomic profiling could more effectively detect tRCC, because the driver fusion constitutes an oncogenic transcription factor that alters gene regulation. By defining a TFE3-driven epigenomic signature in tRCC cell lines and detecting it in patient plasma using chromatin immunoprecipitation and sequencing, we distinguished tRCC from clear cell RCC (AUC=0.87) and healthy controls (AUC=0.91) at low tumor fractions (<1%). This work establishes a framework for non-invasive epigenomic detection, diagnosis and monitoring of tRCC, with implications for other mutationally quiet, fusion-driven cancers. SIGNIFICANCETranslocation renal cell carcinoma (tRCC) is an aggressive fusion-driven subtype of kidney cancer that is frequently misdiagnosed due to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays targeting DNA alterations are suboptimal for use in tRCC due to its paucity of genomic changes. We demonstrate the utility of cell-free chromatin profiling to noninvasively detect and monitor tRCC with high accuracy, a method that could have applicability to other genomically quiet cancers.

genomics↗

bioRxiv2025

Functional organization of multisensory integration network in children and youth with neurodevelopmental disorders predicts clinical sensory issues

Differences in sensory processing in neurodevelopmental conditions, including Autism Spectrum Disorder (ASD) and Attention-deficit/Hyperactivity Disorder (ADHD), cascade into downstream clinical symptomatology. This includes differences in combining sensory information from multiple modalities into a unified percept, known as multisensory integration. Little is known about the functional organization of multisensory network (MSN) in these groups, its relation to clinical sensory issues, or its interaction with other higher-order cortical networks. We examined resting-state fMRI data from 417 participants in the Province of Ontario Neurodevelopmental Network (ASD=174, ADHD=130, Typical Development=113; Mean age=11.96{+/-}4.10). Timeseries data were extracted from the MSN and seven additional resting-state cortical networks (RSNs). Undirected and directed functional connectivity (FC) metrics were computed within the MSN and between the MSN and other RSNs. FC was compared across diagnoses and related to clinical sensory characteristics. The thalamus emerged as a hub region in both undirected and directed FC within the MSN and between the MSN-RSNs. Some diagnosis-related differences were observed, with increased MSN-RSN FC particularly in ADHD; however, associations with sensory characteristics were stronger in both undirected and directed FC within the MSN and between the MSN-RSNs, regardless of diagnosis. Converging evidence was seen in data-driven clusters based on FC metrics, which did not align with diagnosis, but instead mapped on to the overall level of sensory issues reported. That the data-driven clusters sorted not by diagnosis but by sensory characteristics suggests that these sensory characteristics and their underlying neurobiology are transdiagnostic in nature as opposed to specific to ASD or ADHD.

neuroscience↗

bioRxiv2023

Epigenomic signatures as circulating and predictive biomarkers in sarcomatoid renal cell carcinoma

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are (1) a limited understanding of its gene regulatory programs and (2) difficulty identifying sarcomatoid differentiation on tumor biopsies due to spatial heterogeneity. To address these challenges, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries in tissue and plasma samples from 50 patients with RCC and healthy volunteers. We identified highly recurrent epigenomic reprogramming, as assessed by histone modifications and DNA methylation, that distinguishes sRCC from non-sarcomatoid RCC. Computational analysis of RCC epigenomic profiles and CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs. Analysis of two randomized clinical trials identified FOSL1 expression as a predictive biomarker of response to ICIs in RCC. Finally, we demonstrate that epigenomic signatures of sRCC are detectable in patient plasma, establishing an approach for blood-based diagnosis of this clinically important phenotype. These findings provide a framework for the discovery and non-invasive detection of epigenomic correlates of tumor histology via liquid biopsy.

genomics↗

bioRxiv2023

Differential effects of prolonged aerobic and resistance exercise on cognitive functioning in sedentary young adults

ObjectivesInconsistencies in the literature make it difficult to outline the relationship between exercise and cognition in young adults. Our aim is to better understand the relationship between prolonged aerobic and resistance exercise and cognitive abilities in sedentary young adults, and how this relationship is mediated by changes in cardiovascular fitness. MethodsTwenty-three volunteers were recruited and assigned to two groups to complete one hour of continuous daily workout sessions of aerobic (SPIN) and anaerobic (SCSW) exercises over a 30 day period. Each subject was provided with a Polar-10 wearable to record the heart rate (HR) activity during the workout sessions. The workout sessions were completed during five consecutive days over four consecutive weeks. Each week, HR data were collected from the last workout session. Volunteers also completed a neurocognitive test battery (Cambridge Brain Sciences, CBS) each exercise session, including an additional baseline measure before exercise regime began. ResultsWe found that memory, reasoning and verbal abilities improved throughout the aerobic, but not the resistance exercise program. We found a positive correlation between heart rate index (HRI) and memory and reasoning test scores. We also found a negative correlation between reasoning ability and HRM (heart rate mean), and heart rate skewness (SKW). The results of a regression model to predict memory and reasoning abiltiies revealed that memory was best predicted by HRI and HRM, while the reasoning ability was best predicted by only HRI. ConclusionRegular aerobic exercises improved specific cognitive performance and it was possible to predict the performance by employing the HR parameters HRI and HRM.

neuroscience↗