Biology subjects

Roy, E.

Publications and source records attributed to Roy, E..

17 recordsLinked to original sources

bioRxiv2026

Highly replicable multisite patterns of adolescent white matter maturation

The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity--in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI--were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.

neuroscience↗

bioRxiv2025

Methanotroph dynamics at landfill cover soil methane emission hotspots

Landfills contribute significant emissions to the global methane cycle, where emission hotspots can account for the majority of methane released. Methanotrophs in landfill cover soils can mitigate these methane emissions, but are constrained by geochemical conditions in the soils and the climate at the landfills location. We sampled cover soils from four Ontario landfills with differing characteristics, including measurements of methane flux, soil methane concentration, and a suite of geochemical variables. Sampling sites were distinguished based on the levels of methane flux. Microbial community diversity and methanotroph dynamics were examined using 16S rRNA gene amplicon sequencing. Sites with high methane emissions showed strong enrichment of methanotrophs, dominated by the genus Methylomicrobium. The distribution of methanotrophs in samples across landfills and sites differed significantly when considering community evenness. Of the environmental factors examined, microbial community diversity correlated most strongly to nitrate and nitrite concentrations. Methanotroph dynamics across different methane exposures and geochemical conditions within landfill cover soils inform the use of designer cover soils and/or methanotroph amendments in efforts toward mitigating methane emissions from landfills.

microbiology↗

bioRxiv2025

Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner

The accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimers disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the brain remain poorly understood. Here, we selectively expressed non-mutated or mutated human microtubule-associated protein tau (hMAPT) in neurons across the brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau. Single-nuclei RNA sequencing confirmed a selective loss of hippocampal excitatory neurons by the wild-type tau and revealed the upregulation of neurodegeneration-related pathways in the affected populations. The accumulation of phosphorylated tau was accompanied by cellular stress in neurons and reactive gliosis in multiple brain regions. Notably, the lifelong absence of microglia significantly and differentially influenced the extent of neurodegeneration in the hippocampus and thalamus. Therefore, our study established an AD-relevant tauopathy mouse model, elucidated both neuron-intrinsic and neuron-extrinsic responses, and highlighted critical and complex roles of microglia in modulating tau-driven neurodegeneration.

neuroscience↗

bioRxiv2024

Development of the Left Arcuate Fasciculus is Linked to Learning Gains in Reading, but not Math

Past studies leveraging cross-sectional data have raised questions surrounding the relationship between diffusion properties of the white matter and academic skills. Some studies have suggested that white matter properties serve as static predictors of academic skills, whereas other studies have observed no such relationship. On the other hand, longitudinal studies have suggested that within-individual changes in the white matter are linked to learning gains over time. In the present study, we look to replicate and extend the previous longitudinal results linking longitudinal changes in the white matter properties of the left arcuate fasciculus to individual differences in reading development. To do so, we analyzed diffusion MRI data, along with reading and mathematics scores in a longitudinal sample of 340 students as they progressed from 1st grade into 4th grade. Longitudinal growth models revealed that year-to-year within-individual changes in reading scores, but not math, were related to the development of the left arcuate fasciculus. These findings provide further evidence linking the dynamics of white matter development and learning in a unique sample and highlight the importance of longitudinal designs.

neuroscience↗

bioRxiv2024

Fate-mapping and functional dissection reveal perilous influence of type I interferon signaling in mouse brain aging

Although aging significantly elevates the risk of developing neurodegenerative diseases, how age-related neuroinflammation preconditions the brain toward pathological progression is ill-understood. To comprehend the scope of type I interferon (IFN-I) activity in the aging brain, we surveyed IFN-I-responsive reporter mice and detected age-dependent signal escalation in multiple brain cell types from various regions. Selective ablation of Ifnar1 from microglia in aged mice significantly reduced overall brain IFN-I signature, dampened microglial reactivity, lessened neuronal loss, and diminished the accumulation of lipofuscin, a core hallmark of cellular aging in the brain. Overall, our study demonstrates pervasive IFN-I activity during normal mouse brain aging and reveals a pathogenic role played by microglial IFN-I signaling in perpetuating neuroinflammation, neuronal dysfunction, and molecular aggregation. These findings extend the understanding of a principal axis of age-related inflammation in the brain, and provide a rationale to modulate aberrant immune activation to mitigate neurodegenerative process at all stages.

neuroscience↗

bioRxiv2023

Effects of atmospheric CO2 concentration on transpiration and leaf elongation responses to drought in wheat, perennial ryegrass and tall fescue

We studied the effects of atmospheric CO2 concentration ([CO2]) on the leaf growth response to drought in perennial ryegrass, tall fescue and wheat. Plants were grown in growth chambers at either 200 or 800 ppm of CO2. At leaf 6-7 unfolding, half of the plants were subjected to severe drought. Leaf elongation rate (LER) was measured daily, while plant transpiration was continuously recorded gravimetrically. Water-soluble carbohydrate concentration, water and osmotic potentials in the leaf growing zone were measured at drought onset, at mid-drought and at the time of leaf growth cessation. [CO2] caused stomata closure and therefore reduction of instantaneous transpiration rate and water loss. As a result, CO2 mitigated the impacts of drought on LER and delayed growth cessation for all three species. For ryegrass, LER and soil relative water content (SRWC) relation was improved with CO2, presumably due to a better stomatal regulation. CO2 did not affect nighttime water potential nor osmotic potential of the growing zone. Related to leaf growth, we observed the main effect of CO2 on tillering but no effect on the plant development. In total, water consumption was similar (wheat, tall fescue) or greater (ryegrass) with CO2.

plant biology↗

bioRxiv2023

Educational Environment and White Matter Development in Early Adolescence

Coarse measures of socioeconomic status, such as parental income or parental education, have been linked to differences in white matter development. However, these measures do not provide insight into specific aspects of an individuals environment and how they relate to brain development. On the other hand, educational intervention studies have shown that changes in an individuals educational context can drive measurable changes in their white matter. These studies, however, rarely consider socioeconomic factors in their results. In the present study, we examined the unique effect of educational opportunity on white matter development, even when controlling other known socioeconomic factors. To explore this question, we leveraged the rich demographic and neuroimaging data available in the ABCD study, as well the unique data-crosswalk between ABCD and the Stanford Education Data Archive (SEDA). We find that educational opportunity is related to accelerated white matter development, even when accounting for other socioeconomic factors, and that this relationship is most pronounced in white matter tracts associated with academic skills. These results suggest that the school a child attends has a measurable impact on brain development for years to come.

neuroscience↗

bioRxiv2023

Morphogen-driven human iPSCs differentiation in 3D in vitro models of gastrulation is precluded by physical confinement.

In early human development, gastrulation is tightly associated with lineage specification. The interplay between mechanical forces and biochemical signals during these processes is poorly understood. Here, we dissect the effects of biochemical cues and physical confinement on a 3D in vitro model of gastrulation that uses spheroids formed from human induced pluripotent stem cells (hiPSCs). First, we compare self-renewing versus differentiating media conditions in free-floating cultures, and observe the emergence of organised tri-germ layers. In these unconfined cultures, BMP4 exposure induces polarised expression of SOX17 in conjunction with spheroid elongation. We then physically confine spheroids using PEG-peptide hydrogels and observe dramatically reduced SOX17 expression, albeit rescued if gels that soften over time are used instead. Our study combines high-content imaging, synthetic hydrogels and hiPSCs-derived models of early development to define the drivers causing changes in shape and emergence of germ layers.

cell biology↗

bioRxiv2022

Development of the alpha rhythm is linked to visual white matter pathways and visual detection performance

Alpha is the strongest electrophysiological rhythm in awake humans at rest. Despite its predominance in the EEG signal, strong variations can be observed in alpha properties during development, with an increase of alpha frequency over childhood and adulthood. Here we tested the hypothesis that these changes of alpha rhythm are related to the maturation of visual white matter pathways. We capitalized on a large dMRI-EEG dataset (dMRI n=2,747, EEG n=2,561) of children and adolescents (age range: 5-21 years old) and showed that maturation of the optic radiation specifically accounts for developmental changes of alpha frequency. Behavioral analyses also confirmed that variations of alpha frequency are related to maturational changes in visual perception. The present findings demonstrate the close link between developmental variations in white matter tissue properties, electrophysiological responses, and behavior.

neuroscience↗

bioRxiv2022

Role of EnvC and the phosphoenolpyruvate:sugar phosphotransferase system in resistance to MreB disruption

Cell wall synthesis in bacteria is determine by two protein complexes: the elongasome and divisome. The elongasome is coordinated by the actin homolog MreB while the divisome is organized by the tubulin homolog FtsZ. While these two systems must coordinate with each other to ensure that elongation and division are coregulated, this cross talk has been understudied. Using the MreB depolymerizing agent, A22, we found that multiple gene deletions result in cells exhibiting increased sensitivity to MreB depolymerization. One of those genes encodes for EnvC, a part of the divisome that is responsible for splitting daughter cells after the completion of cytokinesis through the activation of specific amidases. Here we show this increased sensitivity to A22 works through two known amidase targets of EnvC: AmiA and AmiB. In addition, suppressor analysis revealed that mutations in the phosphoenolpyruvate:sugar phosphotransferase system (PTS) can suppress the effects of A22 in both wild-type and envC deletion cells. Together this work helps to link elongation, division, and metabolism.

microbiology↗

bioRxiv2022

White matter and literacy: a dynamic system in flux

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individuals educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to reading skills over development or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N=14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the single-observation datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

neuroscience↗

bioRxiv2022

An open, analysis-ready, and quality controlled resource for pediatric brain white-matter research

We created resources to facilitate research on the role of human brain microstructure in the development of mental health disorders, based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N=2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI, and we provide automated quality control (QC) scores for every scan, as part of the data release. To scale QC to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC = 0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers a resource for transdiagnostic research in brain connectivity and pediatric mental health and serves as a novel tool for automated QC of large datasets.

neuroscience↗

bioRxiv2021

Dominant Effect Of Host Genetics On Skin Microbiota Composition In Homeostasis And Wound Healing

Animal microbiota have complex interactions with hosts and environment that determines its composition. Yet the ability of hosts to determine their microbiota composition is less well studied. In this study, to investigate the role host genetics in determining skin microbiota, we used 30 different mouse strains from the recombinant inbred panel, the Collaborative Cross. Murine skin microbiota composition was strongly dependent on murine strain with > 50% of the variation explained by murine strain. In particular, a quantitative trait locus on chromosome 4 associates both with Staphylococcus abundance and principal-component multi-trait analyses. Additionally, excisional wound associated changes in microbiota composition were not uniform across mouse strains and were host-specific, the genetic background accounting for about 40% of the variation in microbiota. Genetic background also had the highest effect on the healing speed of wounds accounting for over 50% of the variation while mouse age and microbiota composition change accounted only for 20% and 5% of the healing speed despite reaching statistical significance. In conclusion, host genetics has a significant impact on the skin microbiota composition during both homeostasis and wound healing. These findings have long reaching implications in our understanding of associations between microbiota dysbiosis and disease.

systems biology↗

bioRxiv2021

Evaluating the reliability of human brain white matter tractometry

The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connections in vivo, in part based on reliability of the analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to demonstrate the reliability of computational analysis pipelines in neuroimaging.

neuroscience↗

bioRxiv2020

High Content Analysis uncovers functionally relevant metastable phenotypic states in human Endothelial Cells monolayers

Endothelial cells (EC) are heterogeneous across and within tissues, reflecting distinct, specialised functions. EC heterogeneity has been proposed to underpin EC plasticity independently from vessel microenvironments. However, heterogeneity driven by contact-dependent or short-range cell-cell crosstalk cannot be evaluated with single cell transcriptomic approaches as spatial and contextual information is lost. Nonetheless, quantification of EC heterogeneity and understanding of its molecular drivers is key to developing novel therapeutics for cancer, cardiovascular diseases and for revascularisation in regenerative medicine. Here, we developed an EC profiling tool (ECPT) to examine individual cells within intact monolayers. We used ECPT to characterise different phenotypes in arterial, venous and microvascular EC populations. In line with other studies, we measured heterogeneity in terms of cell cycle, proliferation, and junction organisation. ECPT uncovered a previously under-appreciated single-cell heterogeneity in NOTCH activation. We correlated cell proliferation with different NOTCH activation states at the single cell and population levels. The positional and relational information extracted with our novel approach is key to elucidating the molecular mechanisms underpinning EC heterogeneity. Summary statementEndothelial cells heterogeneity is key to complex collective functions and cell behaviour. We developed a novel image based endothelial cell profiling tool and quantified heterogeneity in NOTCH signalling in monolayers.

cell biology↗

bioRxiv2020

Chikungunya Virus Infection Impairs The Function Of Osteogenic Cells

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, spread by the Aedes species (sp.) mosquitoes. Chikungunya virus (CHIKV) causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal presence of bone lesions and erosive arthritis in the joints of CHIKV infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs lead to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. To our knowledge, for the first time we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed a decreased gene expression of the major regulator of osteogenic differentiation, RUNX2 in CHIKV infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells i.e. decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection. ImportancePresently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection and infection likely alters function of the osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

microbiology↗

bioRxiv2019

Chikungunya virus infection impairs osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, belonging to the genus alphavirus in the family Togaviridae. The virus is spread by the Aedes species (sp.) mosquitoes in tropical and subtropical regions of the world. CHIKV causes Chikungunya fever (CHIKF), where the acute stage of infection is characterized by high fever, headache, rash, and polyarthralgia. In 30-40% of cases, patients develop a chronic stage with debilitating joint pain persisting for months to years imposing a burden on the population in terms of disability adjusted life years (DALY). Presently, no vaccines or treatment options are available for this infection. Prior investigations reveal that CHIKV infection is associated with bone pathology; however, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Studies show that disruption of osteogenic differentiation and function of bone marrow-derived mesenchymal stem cells (BMMSCs) can lead to bone pathologies. However, to date pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMMSCs to CHIKV and studied the effect of infection on BMMSCs-derived osteogenic cells. To our knowledge, for the first time we report that CHIKV can productively infect BMMSCs. We observed a decrease in the intracellular and extracellular alkaline phosphatase (ALP) activity and reduction in calcium phosphate deposition in infected cells compared to mock-infected control. Thus, we conclude that CHIKV infects BMMSCs and disrupts function of osteogenic cells.\n\nImportanceAlthough studies have shown association of bone pathology and CHIKV infection, the pathogenesis of infection causing altered bone homeostasis is not fully understood. Here, we demonstrate for the first time that BMMSCs are susceptible to CHIKV infection. Furthermore, we observe that infection causes disruption in the function of BMMSC- derived osteogenic cells. Impaired function of these osteogenic cells will likely lead to a disruption in bone homeostasis and in part, provides a mechanism for the observed bone pathology associated with CHIKV pathogenesis.

microbiology↗