Biology subjects

Boyer, M.

Publications and source records attributed to Boyer, M..

8 recordsLinked to original sources

bioRxiv2026

Graph-Based Classification of Penetrating Arteries and Veins in Whole-Mouse Vasculature Datasets

Advances in whole-brain imaging have produced large-scale vascular datasets, yet most lack artery-vein annotations. However, this is essential for quantitative analysis of whole brain vascular structure, blood flow simulation and translational cerebrovascular research. For unlabelled datasets, manual labelling is infeasible at network scale, and surface-vessel tracing is hampered by reconstruction artefacts, limiting the insights that can be gained from these datasets. Here, we focus on penetrating vessel trees, i.e. descending arteries (A) and ascending veins (V). A supervised Random Forest classifier is trained on graph-derived morphological and topological tree features, including persistent homology. Training uses datasets from two imaging modalities: Light sheet (LS) microscopy with arterial staining and two-photon (TP) micrscopy with manual labelling in smaller samples. Classification reached 96% balanced accuracy on independent TP dataset and 93% on LS datasets. Topological features alone achieved competitive accuracy without relying on diameter measurements, demonstrating cross-modality portability. Arteries exhibit larger diameters and longer inter-bifurcation segments, likely facilitating their functional task of directed blood delivery. The veins show greater branching complexity, allowing low-pressure drainage. These signatures are stable across modalities, supporting their physological relevance. The framework enables A-V label transfer to unlabelled whole-brain TP graph datasets, validated through the V:A ratio as a function of middle cerebral artery (MCA) distance. Operating on graph representations derived from any volumetric imaging modality and requiring no retraining, the approach is applicable to LS, TP, and likely other imaging platforms, providing a scalable foundation for A-V quantification, vascular topological analysis, and haemodynamic modelling.

neuroscience↗

bioRxiv2026

SynAPSeg: A novel dataset and image analysis framework for deep learning-based synapse detection and quantification

Synapses are the fundamental units of neural computation, yet quantifying their organization across circuit-level scales remains a critical bottleneck in neuroscience. While advances in fluorescent labeling and imaging can generate vast datasets, analysis is often the limiting factor. Several deep learning-based tools have been proposed to ameliorate these issues. However, existing applications primarily focus on dendritic spines and lack robust solutions for segmenting synaptic puncta in dense tissue preparations. To address this, we introduce SynAPSeg, which encompasses an open-source framework for deep learning-based analysis and, to the best of our knowledge, the first large-scale, publicly available instance segmentation dataset specifically curated for synaptic puncta. We use this dataset to train deep learning models that reach the performance of human experts across a unique benchmark dataset. SynAPSeg integrates these models into an interactive interface, with support for multi-dimensional data, enabling fully automated segmentation and quantification pipelines alongside an annotation module for refinement and validation. We demonstrate the frameworks scalability by performing the first comprehensive mapping of nearly 4 million excitatory postsynaptic PSD95 puncta within inhibitory interneurons across the dorsal hippocampus, revealing regional differences in synapse properties. Finally, we show SynAPSegs utility for 3D quantification by applying these models to study aging-associated synaptic changes in CA1 parvalbumin (PV)-positive inhibitory neurons. Through this approach, we uncover a reduction in PSD95 density along PV dendrites in the aged CA1, indicating reduced glutamatergic recruitment of PV neurons which could contribute to age-related cognitive decline. Collectively, these results demonstrate that SynAPSeg provides a scalable solution for comprehensively studying synaptic architecture in health and disease.

neuroscience↗

bioRxiv2025

Astrocytic activation of EMMPRIN contributes to their pathological phenotype in ALS.

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterised by the degeneration of upper and lower motoneurons. Onset and progression of the disease are determined by both cell-autonomous neuronal dysfunctions and non-cell-autonomous factors, mainly due to activation of glial cells such as astrocytes and microglia. The Extracellular Matrix Metalloproteinases INducer (EMMPRIN), a glycoprotein expressed by various cell types including neurons, is the major activator of matrix metalloproteinases (MMPs) synthesis and release. EMMPRIN activation can be induced by peptidyl-prolyl isomerase A (PPIA), a chaperone protein with cis/trans isomerase activity, that exhibits cytokine- and chemokine-like behaviour. Previous studies showed that PPIA is highly released in the cerebrospinal fluid (CSF) of ALS patients and animal models where, by activating EMMPRIN on motoneurons, induces neuronal death. Here, we show that EMMPRIN is expressed also by astrocytes, suggesting this cell type as sensitive as motoneurons to PPIA-mediated EMMPRIN activation. We observed that that PPIA-mediated EMMPRIN activation prompt astrocytes toward a pro-inflammatory profile. Interestingly, we found that this pathogenic profile can be reverted by an anti-EMMPRIN antibody. Finally, we provide evidence that the activation of EMMPRIN is relevant for mutant SOD1 and TDP-43 conditions. In conclusion, we demonstrate that EMMPRIN activation in ALS occurs also in astrocytes where it exacerbates their pathological phenotype possibly contributing to the progression of the disease. Furthermore, we suggest the potential use of an anti-EMMPRIN antibody to reduce astrocytic activation during the disease.

neuroscience↗

bioRxiv2024

Functional carbohydrate-active enzymes acquired by horizontal gene transfer from plants in the whitefly Bemisia tabaci

Carbohydrate-active enzymes (CAZymes) involved in the degradation of plant cell walls and/or the assimilation of plant carbohydrates for energy uptake are widely distributed in microorganisms. In contrast, they are less frequent in animals, although there are exceptions, including examples of CAZymes acquired by horizontal gene transfer (HGT) from bacteria or fungi in several of phytophagous arthropods and plant-parasitic nematodes. Although the whitefly Bemisia tabaci is a major agricultural pest, knowledge of HGT-acquired CAZymes in this phloem-feeding insect of the Hemiptera order (subfamily Aleyrodinae) is still lacking. We performed a comprehensive and accurate detection of HGT candidates in B. tabaci and identified 136 HGT events, 14 of which corresponding to CAZymes. The B. tabaci HGT-acquired CAZymes were not only of bacterial or fungal origin, but some were also acquired from plants. Biochemical analysis revealed that members of the glycoside hydrolase families 17 (GH17) and 152 (GH152) acquired from plants are functional beta-glucanases with different substrate specificities, suggesting distinct roles. These two CAZymes are the first characterized GH17 and GH152 glucanases in an animal. We identified a lower number of HGT events in the related Aleyrodinae Trialeurodes vaporariorum, with only three HGT-acquired CAZymes, including a GH152 glucanase, with phylogenetic analysis suggesting a unique HGT event in the ancestor of the Aleyrodinae. Another GH152 CAZyme, most likely independently acquired from plants, was also identified in two plant cell-feeding insects of the Thysanoptera order, highlighting the importance of plant-acquired CAZymes in the biology of piercing-sucking insects. Significance statementCarbohydrate-active enzymes (CAZymes) are crucial for sugar metabolism. Those involved in plant cell wall degradation are usually absent from animal genomes. In this study, we explored CAZyme repertoires in the genomes of several insects: the phloem-feeding whitefly Bemisia tabaci, a major agricultural pest, and the related greenhouse whitefly Trialeurodes vaporariorum, as well as two Thysanoptera species that feed on plant cell contents. We identified several cases of CAZymes acquired from plant via horizontal gene transfer in the genome of these insects. Notably, we showed that two B. tabaci CAZymes of plant origin function as glucanases with distinct substrate specificities, potentially helping the insect to overcome plant defenses. Overall, these findings enhance our understanding of how the ability to feed on plants evolved in insects.

evolutionary biology↗

bioRxiv2024

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers.

Survival in recurrent/metastatic head and neck mucosal squamous cell carcinoma (HNmSCC) remains poor. Anti-programmed death (PD)-1 therapies have demonstrated improved survival with lower toxicity when compared to standard chemotherapy. However, response to anti-PD-1 therapy remains modest, at 13-17%. We evaluated the tumor microenvironment (TME) using Imaging Mass Cytometry (IMC) on 27 tumor specimens from 24 advanced HNmSCC patients prior to receiving anti-PD-1 based treatment. We show significantly increased central memory T cells and B cells in responders (n=8) when compared to non-responders (n=16). Spatial mapping identified interactions between phenotypically distinct malignant squamous cells with CD8+ T cells, CD4+ Tregs and endothelial cells in responders, and avoidance of these cells in non-responders. Importantly, regional analysis shows responders have more abundant tertiary lymphoid structures (TLS), with TLS proportion >20% also associated with longer progression free survival. Together these findings define the immune landscape associated with response to anti-PD-1 treatment in HNmSCCs.

cancer biology↗

bioRxiv2024

Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias

BackgroundIntramyocardial injection of human pluripotent stem cell-derived cardiomyocytes following a myocardial infarction (MI) improves cardiac function in large animal models, but associated ventricular arrhythmias are major safety concern. We hypothesized that transendocardial injection of human induced pluripotent stem cell (hiPSC)-derived committed cardiac progenitor cells (CCPs), combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention, will generate cardiac tissue grafts improving contractility without triggering ventricular arrhythmias. MethodshiPSCs were differentiated using bioreactors and small molecules to produce committed cardiac progenitor cells (CCPs). MI was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, epicardial needle injections of CCPs+cECM were performed in a small initial feasibility cohort (n=6), and then transendocardial injections of CCPs+cECM (n=14), CCPs alone (n=14), cECM alone (n=4) or vehicle control (n=13) into the peri-infarct region in a randomized cohort. Arrhythmias were evaluated using implanted event recorders. Magnetic resonance imaging (MRI) and invasive pressure-volume assessment were used to evaluate left ventricular anatomic and functional performance. Detailed histology was performed to detect and characterize human grafts. ResultsA scalable biomanufacturing protocol was developed generating CCPs which can efficiently differentiate into cardiomyocytes or endothelial cells in vitro. Intramyocardial delivery of CCPs to post-MI porcine hearts resulted in engraftment and differentiation of CCPs to form ventricular cardiomyocyte rich grafts. There was no significant difference in cardiac MRI-based measured cardiac volumes or function between control, CCP and CCP+cECM groups; however, pressure-volume analysis showed an improvement in dobutamine-stimulated functional reserve in CCP and CCP+cECM groups. Delivery of CCPs did not result in tumors or ventricular arrhythmias. ConclusionsTransendocardial delivery of CCPs with or without cECM into post-MI porcine hearts resulted in comparable human cardiomyocyte grafts which did not improve resting LV function but did improve stress-induced contractile reserve without triggering ventricular arrhythmias.

pathology↗

bioRxiv2023

TNF and type I IFN induction of the IRG1-itaconate pathway restricts Coxiella burnetiireplication within mouse macrophages

The intracellular Gram-negative bacterium Coxiella burnetii replicates within macrophages and causes a zoonotic disease known as Q fever. In murine macrophages, the cytokine tumor necrosis factor (TNF) is critical for restriction of intracellular C. burnetii replication. Here, we show that TNF collaborates with type I interferon (IFN) signaling for maximal control of C. burnetii. We found that TNF and type I IFN upregulate the expression of the metabolic enzyme immune responsive gene 1 (IRG1), also known as cis-aconitate decarboxylase 1 (ACOD1), and that IRG1 is required to restrict C. burnetii T4SS translocation and replication within macrophages. Further, we show that itaconic acid, the metabolic product of IRG1, restricts C. burnetii replication both intracellularly and in axenic culture. These data reveal that TNF and type I IFN upregulate the IRG1-itaconate pathway to restrict intracellular C. burnetii replication within murine macrophages.

microbiology↗

bioRxiv2022

In vivo low-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity.

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons in vivo. Continuous 10 Hz LI-rTMS reliably evoked firing at [~]4-5 Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce LI-rTMS effects on neuronal properties. These data provide novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability.

neuroscience↗