Biology subjects

Poirier, C.

Publications and source records attributed to Poirier, C..

15 recordsLinked to original sources

bioRxiv2026

Tractography from Serial Optical Coherence Tomography: How and Why?

To disentangle complex fiber configurations that remain challenging for diffusion MRI tractography, insights might be gained from microscopy tractography. Indeed, by precisely following small white matter (WM) fascicles, invisible at the resolution of diffusion MRI, microscopy tractography can help explain how fiber populations are organized at the finest scales. Due to its high resolution and its 3D nature, serial optical coherence tomography (S-OCT) offers promise for studying WM at the microscale. However, whether the reflectivity contrast from S-OCT supports tractography at the microscale remains unknown. Furthermore, there is a gap in the literature regarding how an ideal microscopy tractography algorithm should behave with respect to the choice of tractography algorithm, tracking maps definition and microscale orientation distribution functions (ODF) estimation. In this work, we describe a tailored approach to reconstruct WM fascicles at the microscale from S-OCT acquisitions. We validate our approach on a simulated microscopy-like FiberCup dataset, and show that multiscale Frangi filters outperforms structure tensor analysis for estimating ODF. We also show that anatomically-constrained particle filtering tractography enables targetted, region-to-region tractography, and outperforms standard deterministic or probabilistic tracking approaches. We further demonstrate our method on a whole mouse brain S-OCT reconstruction at 10 m by reconstructing thalamocortical WM projections. Overall, our results show that S-OCT tractography recovers fine white matter fascicles that are supported by viral tracing experiments from the Allen Mouse Brain Connectivity Atlas. Moreover, this work shows the first ODF estimation and fully-3D probabilistic particle filtering tractography of the mouse brain from S-OCT reconstructions at 10 m isotropic resolution.

bioinformatics↗

bioRxiv2025

Effect of fluid control on the affective state of laboratory macaques

Fluid control protocols are widely used in neuroscience to motivate laboratory macaques to engage with behavioural tasks. Despite strong evidence that the physiology of the animals is not compromised by such protocols, fluid control remains controversial due to its potential impact on the psychological well-being of the animals. To address this concern, we investigated the effect of fluid control on the affective state of 23 socially-housed adult macaques (10 females) engaged in neuroscience experiments. The protocol involved up to five consecutive days of fluid control per week, followed by a minimum of two days with unrestricted fluid access. The affective state of the animals was primarily assessed by quantifying the frequency of pharmacologically-validated behavioural indicators of high-arousal negative affect (self-scratching, body shaking, self-grooming). The analysis was subsequently extended to validated behavioural indicators of low-arousal negative affect (Inactive not alert) and other behaviours suspected of indicate high-arousal negative affect but lacking proper validation (pacing, yawning). In total, 700 hours of video footage spanning up to seven years of intermittent fluid control per animal were analysed. Despite this extensive dataset, the study found no significant impact of fluid control on average, or any evidence of habituation or sensitization over the years on any of the affective state indicators. Additional results indicate that these null results are not due to a lack of sensitivity, supporting the view that fluid control, as implemented in this study, does not have an adverse impact on the psychological well-being of laboratory macaques. We argue that macaque welfare will be best served by focusing future refinement on other procedures.

animal behavior and cognition↗

bioRxiv2025

Proof-of-principle of NF1 Gene Therapy in plexiform neurofibroma mice models

Neurofibromatosis type I is a rare neurocutaneous syndrome characterized by the development of disfiguring neurofibroma tumors with unmet clinical needs. As Neurofibromatosis Type I is a monogenic disease, the development of gene therapy is highly attractive, but it is currently unknown if rescuing the NF1 gene in established neurofibroma is sufficient for tumor regression. Here, we test this hypothesis by building two novel NF1 mouse models with reversible NF1 expression. In the first model, the human NF1 -/- Schwann cells named ipNF95.11b were genetically modified with a doxycycline-inducible full-length mouse Nf1 gene. One month after cells implantation in the sciatic nerve, mice were split into 2 groups. Strikingly, all sciatic nerves from mice allowed to drink doxycycline water for one month display complete normalization of the sciatic nerve histologically (n=6 sciatic nerves) whereas 83% (5 out of 6 sciatic nerves) develop or maintain a neurofibroma when drinking regular water. In the second model, the human NF1 +/- Schwann cells named ipNF95.11c were genetically modified with a doxycycline-inducible potent shRNA against the NF1 mRNA transcript. Strikingly, doxycycline withdrawal after neurofibroma establishment allowed complete normalization (n=4 sciatic nerves), whereas all sciatic nerves showed evidence of neurofibroma when kept on doxycycline (n=4 sciatic nerves). Thus, we proof-of-principle NF1 Gene Therapy in plexiform neurofibroma mice models.

cancer biology↗

bioRxiv2024

MacqD - A Deep Learning-based Model for Automatic Detection of Socially-housed Laboratory Macaques

Despite advancements in video-based behaviour analysis and detection models for various species, existing methods are suboptimal to detect macaques in complex laboratory environments. To address this gap, we present MacqD, a modified Mask R-CNN model incorporating a SWIN transformer backbone for enhanced attention-based feature extraction. MacqD robustly detects macaques in their home-cage under challenging scenarios, including occlusions, glass reflections, and overexposure to light. To evaluate MacqD and compare its performance against pre-existing macaque detection models, we collected and analysed video frames from 20 caged rhesus macaques at Newcastle University, UK. Our results demonstrate MacqDs superiority, achieving a median F1-score of 99% for frames with a single macaque in the focal cage (surpassing the next-best model by 21%) and 90% for frames with two macaques. Generalisation tests on frames from a different set of macaques from the same animal facility yielded median F1-scores of 95% for frames with a single macaque (surpassing the next-best model by 15%) and 81% for frames with two macaques (surpassing the alternative approach by 39%). Finally, MacqD was applied to videos of paired macaques from another facility and resulted in F1-score of 90%, reflecting its strong generalisation capacity. This study highlights MacqDs effectiveness in accurately detecting macaques across diverse settings.

animal behavior and cognition↗

bioRxiv2024

Immune-like glycan-sensing and horizontally-acquired glycan-processing orchestrate host control in a microbial endosymbiosis

Endosymbiosis was a key factor in the evolution of eukaryotic cellular complexity. Yet the mechanisms that allow host regulation of intracellular symbionts, a pre-requisite for stable endosymbiosis and subsequent organelle evolution, are largely unknown. Here, we describe an immune-like glycan-sensing/processing network, partly assembled through horizontal gene-transfers (HGTs), that enables Paramecium bursaria to control its algal endosymbionts. Using phylogenetics, RNA-interference (RNAi), and metabolite exposure experiments, we show that P. bursaria regulates endosymbiont destruction using glycan-sensing/processing - a system that includes a eukaryotic-wide chitin-binding chitinase-like protein (CLP) localized to the host phago-lysosome. RNAi of CLP alters expression of eight glycan-processing genes, including two prokaryote-derived HGTs, during endosymbiont destruction. Furthermore, glycan-sensing/processing dynamically regulates endosymbiont number in P. bursaria, plasticity crucial to maximize host fitness across ecological conditions. CLP is homologous to a human phagocyte-associated innate immune factor, revealing how immune functions can be alternatively adapted and expanded, partly through HGT, enabling endosymbiotic control. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/613017v2_ufig1.gif" ALT="Figure 1"> View larger version (77K): org.highwire.dtl.DTLVardef@13aeaaorg.highwire.dtl.DTLVardef@302e6dorg.highwire.dtl.DTLVardef@138224forg.highwire.dtl.DTLVardef@54aca8_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2024

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗

bioRxiv2023

3D-intrusions transport active surface microbial assemblages to the dark ocean

Subtropical oceans contribute significantly to global primary production, but the fate of the picophytoplankton that dominate in these low nutrient regions is poorly understood. Working in the subtropical Mediterranean, we demonstrate that subduction of water at ocean fronts generates 3D intrusions with uncharacteristically high carbon, chlorophyll, and oxygen that extend below the sunlit photic-zone into the dark ocean. These contain "fresh" picophytoplankton assemblages that resemble the photic-zone regions where the water originated. Intrusions propagate depth-dependent seasonal variations in microbial assemblages into the ocean interior. Strikingly, the intrusions included dominant biomass contributions from non-photosynthetic bacteria and enrichment of enigmatic heterotrophic bacterial lineages. Thus, the intrusions not only deliver material that differs in composition and nutritional character from sinking detrital particles, but also drive shifts in bacterial community composition, organic matter processing, and interactions between surface and deep communities. Modeling efforts paired with global observations demonstrate that subduction can flux similar magnitudes of particulate organic carbon as sinking export, but is not accounted for in current export estimates and carbon cycle models. Intrusions formed by subduction are a particularly important mechanism for enhancing connectivity between surface and upper mesopelagic ecosystems in stratified subtropical ocean environments that are expanding due to the warming climate.

ecology↗

bioRxiv2023

Mapping caudolenticular gray matter bridges in the human brain striatum through diffusion magnetic resonance imaging and tractography

In primates, the putamen and the caudate nucleus are connected by [~]1mm-thick caudolenticular gray matter bridges (CLGBs) interspersed between the white matter bundles of the internal capsule. Little is understood about the functional or microstructural properties of the CLGBs. In studies proposing high resolution diffusion magnetic resolution imaging (dMRI) techniques, CLGBs have been qualitatively identified as an example of superior imaging quality, however, the microstructural properties of these structures have yet to be examined. In this study, it is demonstrated for the first time that dMRI is sensitive to an organized anisotropic signal oriented in the direction parallel to the CLGBs, suggesting that dMRI could be a useful imaging method for probing the microstructure of the CLGBs. To demonstrate the anisotropic diffusion signal is coherently organized along the extent of the CLGBs and to enable a subsequent CLGB microstructural measurement, a novel tractography algorithm is proposed that utilizes the shape of the human striatum (putamen + caudate nucleus) to reconstruct the CLGBs in 3D. The method is applied to two publicly available and one locally acquired diffusion imaging datasets varying in resolution and imaging quality, thereafter demonstrating that the reconstructed CLGBs directly overlap expected gray matter regions in the human brain. In addition, the method is shown to accurately reconstruct CLGBs repeatedly across multiple test-retest cohorts. The novel tractography CLGB reconstructions are then used to extract a quantitative measurement of microstructure from a local model of the diffusion signal along the CLGBs themselves. This is the first work to comprehensively study the CLGBs in-vivo using dMRI and presents techniques suitable for future human neuroscience studies targeting these structures.

neuroscience↗

bioRxiv2023

AutoMacq: an automatic pipeline to analyse macaque structural MRI data

MRI scanning of rhesus macaques is a growing field due to their evolutionary proximity and similar neuroanatomy to humans. As such, there is a need for automatic macaque MRI processing pipelines. AutoMacq is a pipeline capable of processing rhesus macaque MRI data to produce both voxel-based and surface-based metrics. It involves minimal manual intervention and can be carried out without expert knowledge of macaque neuroanatomy. To test the quality of the pipeline, scans from 74 subjects across 8 different sites were processed. Results indicate that over 87% of tissue segmentations and surfaces were of satisfactory quality to not require additional manual correction. Hemispheric comparisons and analyses of scan-rescan data showed strong reliability of the volumetric and surface-based outputs. Finally, to illustrate potential applications of AutoMacq, the change in grey matter volume with ageing was investigated cross-sectionally using subjects aged 3-15 years (corresponding to adolescence until mid-adulthood). The analysis revealed a linear decrease in grey matter volume with age similar to what has been found in humans, reinforcing the value of rhesus macaques as a model of healthy human ageing.

neuroscience↗

bioRxiv2022

Filtering Methods for Asymmetric ODFs: Where and How Asymmetry Occurs in the White Matter

Numerous filtering methods have been proposed for estimating asymmetric orientation distribution functions (ODFs) for diffusion magnetic resonance imaging (dMRI). It can be hard to make sense of all these different methods, which share similar features and result in similar outputs. The objectives of this work are two-fold: to disentangle the various filtering methods proposed in the past for estimating asymmetric ODFs, and to study the occurrence of asymmetric patterns in dMRI brain acquisitions. Hence, we describe a new filtering equation for estimating asymmetric ODFs resulting from the unification of these previously proposed filtering methods. Our method is distributed as an open-source GPU-accelerated python software to facilitate its integration into any existing dMRI processing pipeline. Following its validation on toy datasets, we apply our method to multi-shell multi-tissue fiber ODF reconstructions for 21 subjects from the Human Connectome Project in test-retest acquisitions. Our results show that our method estimates branching, fanning, bending, ending and other complex asymmetric fiber configurations in less than 2 minutes. Also, our novel number of fiber directions (NuFiD) index reveals that the filtering reduces the number of peak directions in the resulting asymmetric representation. Finally, our MNI-aligned template of asymmetries, describing the degree of asymmetry of each voxel, suggests that at least 60% of brain voxels in a dMRI acquisition contain asymmetric fiber configurations.

bioinformatics↗

bioRxiv2021

Picozoa are archaeplastids without plastid

The endosymbiotic origin of plastids from cyanobacteria gave eukaryotes photosynthetic capabilities and launched the diversification of countless forms of algae. These primary plastids are found in members of the eukaryotic supergroup Archaeplastida. All known archaeplastids still retain some form of primary plastids, which are widely assumed to have a single origin. Here, we used single-cell genomics from natural samples combined with phylogenomics to infer the evolutionary origin of the phylum Picozoa, a globally distributed but seemingly rare group of marine microbial heterotrophic eukaryotes. Strikingly, the analysis of 43 single-cell genomes shows that Picozoa belong to Archaeplastida, specifically related to red algae and the phagotrophic rhodelphids. These picozoan genomes support the hypothesis that Picozoa lack a plastid, and further reveal no evidence of an early cryptic endosymbiosis with cyanobacteria. These findings change our understanding of plastid evolution as they either represent the first complete plastid loss in a free-living taxon, or indicate that red algae and rhodelphids obtained their plastids independently of other archaeplastids.

evolutionary biology↗

bioRxiv2019

Pacing behaviour in laboratory macaques is an unreliable indicator of acute stress.

Pacing behaviour, the most frequent stereotypic behaviour displayed by laboratory rhesus macaques (Macaca mulatta) is often used as an indicator of stress. In this study, we investigated how reliable this welfare indicator is at detecting acute stress by testing the reaction of macaques to the stressful event of being exposed to an agonistic interaction between conspecifics housed in the same room but in a different cage. Pacing, agitated locomotion, and stress-related displacement behaviours were quantified before, during and after agonistic interaction exposure, based on video recordings of 13 socially-housed macaques in their home cage. Displacement behaviours increased after agonistic interaction exposure, confirming that the events were experienced as stressful by the focal individuals. The occurrence of pacing did not increase during or after the agonistic interactions. Instead, agitated locomotion increased during the agonistic interactions. These results suggest either, that pacing as an indicator of acute stress is prone to false negative results, increasing in some stressful situations but not others, or that agitated locomotion has been mistaken for pacing in previous studies and that pacing is in fact unrelated to current acute stress. Both interpretations lead to the conclusion that pacing is unreliable as an indicator of acute stress in laboratory rhesus macaques.

animal behavior and cognition↗

bioRxiv2018

Time calibrated morpho-molecular classification of Nassellaria (Radiolaria)

Nassellaria are marine radiolarian protists belonging to the Rhizaria lineage. Their skeleton, made of opaline silica, exhibit an excellent fossil record, extremely valuable in micro-paleontological studies for paleo-environmental reconstruction. Yet, to date very little is known about the extant diversity and ecology of Nassellaria in contemporary oceans, and most of it is inferred from their fossil record. Here we present an integrative classification of Nassellaria based on taxonomical marker genes (18S and 28S ribosomal DNA) and morphological characteristics obtained by optical and scanning electron microscopy imaging. Our phylogenetic analyses distinguished 11 main morpho-molecular clades relying essentially on the overall morphology of the skeleton and not on internal structures as previously considered. Using fossil calibrated molecular clock we estimated the origin of Nassellaria among radiolarians primitive forms in the Devonian (ca. 420 Ma), that gave rise to living nassellarian groups in the Triassic (ca. 250 Ma), during the biggest diversification event over their evolutionary history. This morpho-molecular framework provides both a new morphological classification easier to identify under light microscopy and the basis for future molecular ecology surveys. Altogether, it brings a new standpoint to improve our scarce understanding of the ecology and worldwide distribution of extant nassellarians.

molecular biology↗

bioRxiv2018

The systemic activin response to pancreatic cancer: Implications for effective cancer cachexia therapy

Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy with high rates of cachexia. Serum activin correlates with PDAC cachexia and mortality, while activin administration causes cachexia in mice. We studied activin in human tumors and in mice with orthotopic or genetic PDAC. Cachexia severity correlated with activin expression in tumor lines. Activins were expressed in both cancer and tumor stromal cells, but also in organs in murine PDAC cachexia. Tumor cells expressed activin-{beta}A, or Inhba, while organs expressed both activin-{beta}A and activin-{beta}B, or Inhbb. PDAC elicits activin expression; PDAC conditioned medium induced activin and atrophy of myotubes. Treatment with the activin trap, ACVR2B/Fc, reduced cachexia and prolonged survival in mice with activin-low tumors, and reduced cachexia in activin-high tumors, without affecting activin expression in organs. Mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not survival. Overall our results indicate that PDAC induces a systemic activin response, leading to cachexia, and that activin targets might include organs beyond muscle. Targeting of both tumor-derived and host-derived activins could improve cachexia therapy.

cancer biology↗

bioRxiv2017

An open resource for nonhuman primate imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience.\n\nUnfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMate Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 13 independent data collections aggregated across 11 sites (total = 98 macaque monkeys). We also outline the unique pitfalls and challenges that should be considered in the analysis of the non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

neuroscience↗