Biology subjects

Simon, F.

Publications and source records attributed to Simon, F..

At least 19 recordsLinked to original sources

bioRxiv2026

REDD1 Regulates MERCS, Protein Synthesis and NMJ Stability in Fast Myofibers During Dexamethasone-Induced Muscle Wasting

Background: Glucocorticoids cause skeletal muscle atrophy preferentially affecting fast glycolytic fibers, but the mechanisms involved in this fiber selectivity is unclear. REDD1 is a glucocorticoid-induced stress protein that limits muscle protein synthesis inducing atrophy. However, it remains unknown whether REDD1 exerts myofiber type-specific effects and through which precise mechanisms it regulates protein synthesis. We investigated the role of myofiber REDD1 expression in dexamethasone (DEX)-induced muscle atrophy, with a particular focus on its involvement in mitochondria-ER contact sites (MERCS), protein synthesis, and neuromuscular junction (NMJ) integrity. Methods: We generated tamoxifen-inducible, muscle-specific REDD1 knockout mice (REDD1fl/flHSA-CreERT2) and compared them with floxed littermates (WT) in a 2x2 design (WT/KO x PBS/DEX, 7 days). We combined single-nucleus RNA sequencing, RNAscope, immunofluorescence, transmission electron microscopy, proximity ligation assay, SUnSET puromycin labelling, western blot and RT-qPCR, and AdenoFATE1-mediated MERCS disruption in C2C12 myotubes. Results: Glucocorticoid receptor and REDD1 transcripts were co-enriched in fast glycolytic fibers mostly atrophied by DEX (~20%). REDD1 deletion in myofiber drove to lower basal muscle mass and fast fiber volume but protected them from DEX-induced atrophy. DEX inhibited protein synthesis (~70%) in WT mice with no matching change in Akt/mTOR-pathway activity. In REDD1 KO mice, protein synthesis was already low and was not affected by DEX. DEX-induced REDD1 expression remodelled mitochondrial network and MERCS in a subcellular compartment-specific manner. The intermyofibrillar MERCS minimum distance shortened in both genotypes reaching pathological distances only in WT mice (WT ~28 --> ~5 nm; KO ~25 --> ~15 nm). Perinuclear MERCS and mitochondria-nuclei distances increased in WT mice only (~18 --> ~45 nm and ~130 --> ~460 nm). In WT mice only, DEX-induced alteration of the perinuclear mitochondrial network was associated with a loss of myonuclei accumulating mt-RNA and exhibiting an anabolic transcriptomic signature notably enriched in sarcomeric transcripts. These findings suggest that REDD1-dependent MERCS remodelling may regulate muscle anabolism beyond the control of mRNA translation, by shaping the myonuclear transcriptome. Finally, REDD1 localised to the NMJ and reduced endplate area during DEX treatment. Interestingly, MERCS were denser in NMJ than in myofiber body and we showed in vitro that FATE1-mediated MERCS disruption was sufficient to reduce protein synthesis and agrin-induced acetylcholine-receptor clustering demonstrating that REDD1 and MERCS are important for NMJ stabilization. Conclusions: Muscle REDD1 links the glucocorticoid response to compartment-specific mitochondrial network remodelling, protein synthesis as well as NMJ stability in fast glycolytic fibers. Our results also show that REDD1 is important for maintaining basal mitochondrial network and protein synthesis homeostasis.

cell biology↗

bioRxiv2026

Local Confinement within Plasma Membrane Nanodomains Drives Constitutive Activity of GPCRs

Many G protein coupled receptors (GPCRs) exhibit constitutive (basal) activity, where they can signal in the absence of ligand binding through spontaneous conformational transitions that facilitate G protein coupling and downstream signaling. This intrinsic baseline activity is critical for cellular homeostasis and can be modulated by the receptors conformational ensemble, membrane organization, and interactions with intracellular effectors. In this study, we use live-cell signaling assays, fluorescence cross-correlation spectroscopy (FCCS), and single-particle tracking (SPT) to investigate how membrane organization influences the basal activity of two class A GPCRs: the M1 muscarinic receptor (M1R) and the adenosine A2A receptor (A2AR). In live-cell signalling assays, M1R showed minimal agonist-independent Ca{superscript 2} responses, while A2AR exhibited significant basal cAMP production that was eliminated by an inverse agonist. FCCS showed that, without ligand, only a small portion of M1R co-diffuses with its cognate G11 protein, whereas a much larger fraction of A2AR co-diffuses with the GS protein. SPT revealed that A2AR, but not M1R, is enriched in slowly diffusing, confined states with spatial scales around 150-200 nm and sensitivity to cholesterol- and raft-modulating agents, consistent with localization in lipid-raft nanodomains. Dual-color tracking and diffusion mapping demonstrated that a significant portion of A2AR and GS share confinement domains under basal conditions, while M1R and G11 only show such co-confinement in the active state. These findings support a model where the co-confinement of GPCRs and G proteins within plasma membrane nanodomains--rather than stable pre-coupled RG complexes-- determines the level of constitutive GPCR activity.

biophysics↗

bioRxiv2026

Analyzing single-molecule dynamics with both complex types of motion and complex transition kinetics: Benchmarking of ExaTrack

Single-particle tracking (SPT) is a tool of growing importance which enables biologists to better understand the dynamics of protein interactions at the single-molecule level and in vivo. However, the stochastic nature of the motion of single molecules, the wide variety of types of motion that they can experience and complex transition kinetics between the different states of motion are challenging factors that complicate the interpretation of SPT data. This article presents and benchmarks the tool ExaTrack. Like previous tools, it can handle particles moving in one or multiple states of motion with transitions between states. Its unique feature is that it can simultaneously handle a wide range of complex types of motion such as diffusive motion, directed motion and confined motion while also managing a variety of transition kinetics such as memoryless first-order transitions or more complex time-dependent state transitions. This manuscript focuses on the benchmarking of ExaTrack on simulated data.

biophysics↗

bioRxiv2025

Condition-dependent, amorphous protein agglomerates control cytoplasmic rheology

Molecular crowding in the bacterial cytoplasm restricts the diffusion of large molecules, impacting cellular processes. However, how nutrient availability influences cytoplasmic rheology is not well understood. With single-particle tracking in Escherichia coli, we observed a threefold variation in the diffusion of a 40-nm particle across exponential growth conditions. Previously suggested determinants of rheology did not account for this variation; instead, we found a strong anticorrelation between the diffusion coefficient and the abundance of amino acid metabolism proteins, persisting upon genetic perturbations and showing that lower diffusion is associated with increased viscoelasticity. Photoactivated light microscopy revealed that some amino acid metabolism proteins form clusters. Electron microscopy showed that these proteins could form amorphous agglomerates at physiological concentrations in vitro, likely driven by their low intrinsic disorder, high compactness and hydropathy score. These findings show that protein agglomerates regulate cytoplasmic rheology in a condition-dependent manner, suggesting an underappreciated level of cytoplasmic organization. HighlightsO_LIDiffusion of 40-nm particles varies threefold across growth conditions in E. coli C_LIO_LICytoplasmic diffusion inversely correlates with COG-E protein abundance COG-E proteins form agglomerates that increase cytoplasmic viscoelasticity C_LIO_LIProtein compactness and hydrophobicity predict condition-dependent crowding effects C_LI

biophysics↗

bioRxiv2025

Gene expression cartography of a developing neuronal structure

The brain is a complex structure comprising thousands to billions of neurons that belong to thousands to millions of different neuronal types. These neurons often come from different progenitor domains and have very diverse developmental histories, yet they need to find their precise location in the brain and integrate into appropriate circuits. Therefore, describing the neuronal parts list of the brain in the form of single-cell mRNA sequencing atlases, while invaluable, lacks the spatial information that is instrumental to brain structures. While a large number of brain single-cell mRNA sequencing atlases have become available over the last years, spatial transcriptomic studies have lagged behind for a variety of reasons. Here, we use a gene expression cartography algorithm, called Novosparc, to reconstruct the spatial distribution of gene expression and cell type localization in a complex, yet tractable, developing brain structure, the Drosophila optic lobe. We generate a three-dimensional atlas of this structure, which we made available through a dedicated website (https://larva3dnovosparc.ijm.fr). This allowed us to identify spatially compartmentalized cell types and spatially patterned genes, to predict hotspots of neuronal cell death and identify the expression of neuronal type-defining transcription factors. Importantly, we identify caveats in such algorithms that could allow for the development of refined versions. Altogether, this work provides an invaluable tool for brain researchers to formulate hypotheses and paves the way for the generation of three-dimensional atlases of more complex brain structures, which will enhance our understanding of how neurons with diverse developmental lineages can integrate to form a functional brain.

developmental biology↗

bioRxiv2025

Label-free Machine Learning Prediction of Chemotherapy on Tumor Spheroids using a Microfluidics Droplet Platform

To rapidly evaluate the effects of anticancer treatments in 3D models, an integrated approach is proposed, combining a droplet-based microfluidic platform for spheroid formation and single-spheroid chemotherapy application, label-free morphological analysis, and machine learning to assess treatment response. Morphological features of spheroids, such as size and color intensity, are extracted and selected using the Multivariate Information-based Inductive Causation (MIIC) algorithm, and used to train a neural network for spheroid classification into viability classes, derived from metabolic assays performed within the same platform as a benchmark. The model was tested on Ewing sarcoma cell line and patient-derived xenograft (PDX) cells, demonstrating robust performance across datasets. It accurately predicts spheroid viability, used to generate dose-response curves and to determine half-maximal inhibitory concentration (IC50) values comparable to traditional biochemical assays. Notably, a model trained on cell line spheroids successfully classifies PDX spheroids, highlighting its adaptability. Compared to convolutional neural network-based approaches, this method works with smaller training datasets and provides greater interpretability by identifying key morphological features. The droplet platform further reduces cell requirements, while single spheroid confinement enhances classification quality. Overall, this label-free experimental and analytical platform is confirmed as a scalable, efficient, and dynamic tool for drug screening.

bioengineering↗

bioRxiv2025

Hair cell population integrity necessary to preserve vestibular function

Vestibular dysfunction constitutes a major medical concern, and regeneration of hair cells (HC) is a primary target of gene therapy aimed at restoring vestibular functions. Thus far, therapeutic trials in animal models targeting vestibular loss associated with genetic diseases have yielded variable and partial results, and the functional identity and quantity of HCs required to restore minimal or normal vestibular function remain undefined. Indeed, direct comparisons between structural pathology and quantitative assessments of vestibular dysfunctions are lacking in humans and are rather limited in animal models, representing a significant gap in current knowledge. Here, we present an innovative methodology to bridge the gap between HC integrity and functional vestibular loss in individuals. Gradual vestibular deficits were induced through a dose-dependent ototoxic lesion, quantified with canal or utricular-specific vestibulo-ocular reflex tests, and were then correlated in all individuals with the loss of type I and type II HCs in different regions of ampulla and macula. Our findings reveal that the structure-function relationship is nonlinear, with lower bound of approximately 50% of HCs necessary to retain minimal vestibular function, and threshold exceeding 80% to preserve normal function, thus shedding light on population coding mechanisms for vestibular response. Our data further support the decisive role of type I, rather than type II, HC in the tested VOR functions.

neuroscience↗

bioRxiv2025

Macrophages restrict tumor permissiveness to immune infiltration by controlling local collagen topography through a Tcf4-Collagen3 fibrotic axis

During tumorigenesis, the extracellular matrix (ECM), which constitutes the structural scaffold of tissues, is profoundly remodeled. While the impact of such remodeling on tumor growth and invasion has been extensively investigated, much less is known on the consequences of ECM remodeling on tumor infiltration by immune cells. By combining tissue imaging and machine-learning, we here show that the localization of T lymphocytes and neutrophils, which orchestrate antitumor immune responses, can be predicted by defined topographical features of fibrillar collagen networks. We further show that these collagen topographies result from the activation of a fibrotic pathway controlled by the transcription factor Tcf4 upon depletion of tumor-associated macrophages at late tumor stages. This pathway promotes the deposition of collagen 3 by both tumor and stromal cells, resulting in intermingled collagen networks that favor intra-tumoral T cell and neutrophil localization. Importantly, analysis of human colorectal cancer public bulk RNAseq databases showed a strong correlation between Tcf4 and collagen 3, as well as between the expression of these genes and tumor infiltration by T lymphocytes and neutrophils, attesting the clinical relevance of our findings. This study highlights the key structural role of macrophages on the tumor extracellular matrix and identifies collagen network topographies as a major regulator of tumor infiltration by immune cells.

immunology↗

bioRxiv2025

Temporal and Notch identity determine layer targeting and synapse location of medulla neurons

How specification mechanisms that generate neural diversity translate into specific neuronal targeting, connectivity, and function in the adult brain is not understood. In the medulla region of the Drosophila optic lobe, neural progenitors generate different neurons in a fixed order by sequentially expressing a series of temporal transcription factors as they age. Then, Notch signaling in intermediate progenitors further diversifies neuronal progeny. Using the Electron Microscopy reconstruction of the adult fly brain, we matched the temporal and Notch identity of medulla neurons with their adult targeting features across the different optic lobe neuropils at synapse resolution, and found that these specification mechanisms are significantly associated with the depth of neuropil targeting in the adult brain, for both local interneurons and projection neurons. We show that this temporal identity-dependent targeting of projection neurons unfolds early in development and is genetically determined. Notably, synapse location in the adult brain of putative medulla neurons can be used to predict their temporal origin. Moreover, synapses of neuronal types from different connectome-predicted functional subsystems are compartmentalized in the different neuropils, suggesting a link between synaptic stratification and specific visual functions. Finally, we show that candidate terminal selector TFs are significantly associated with a specific depth bias in the optic lobe neuropils, providing putative molecular determinants of this targeting. Together, we show that temporal identity and Notch status of medulla neurons can predict their neuropil synapse location, linking their developmental patterning with adult circuit architecture.

developmental biology↗

bioRxiv2024

Detecting directed motion and confinement in single-particle trajectories using hidden variables

Single-particle tracking is a powerful tool for understanding protein dynamics and characterizing microenvironments. As the motion of unconstrained nanoscale particles is governed by Brownian diffusion, deviations from this behavior are biophysically insightful. However, the stochastic nature of particle movement and the presence of localization error pose a challenge for the robust classification of non-Brownian motion. Here, we present aTrack, a versatile tool for classifying track behaviors and extracting key parameters for particles undergoing Brownian, confined, or directed motion. Our tool quickly and accurately estimates motion parameters from individual tracks. Further, our tool can analyze populations of tracks and determine the most likely number of motion states. We show the working range of our approach on simulated tracks and demonstrate its application for characterizing particle motion in cells and for biosensing applications. aTrack is implemented as a stand-alone software, making it simple to analyze track data.

biophysics↗

bioRxiv2024

Morphological and functional convergence of visual projections neurons from diverse neurogenic origins in Drosophila

The Drosophila visual system is a powerful model to study the development of neural circuits. Projection neurons that relay visual information from the lobula part of the optic lobe to the central brain (the lobula columnar neurons-LCNs), are thought to encode different visual features relevant to natural behavior. There are [~]20 classes of LCNs whose projections form highly specific, non-overlapping synaptic domains in the brain called optic glomeruli. Although functional investigations of several LCN circuits have been carried out, very little is known about their developmental origin and the stem cell lineages that generate the LCN subtypes. To address their origin, we used single-cell mRNA sequencing to define the transcriptome of each LCN subtype and identified driver lines that are expressed in specific LCNs throughout development. We show that LCNs originate from neural stem cells in four distinct regions in the fly brain that exhibit different modes of neurogenesis, including the ventral and dorsal tips of the outer proliferation center (tOPC), the ventral tips of the inner proliferation center (vtIPC) and the central brain (CB). This convergence of similar neurons illustrates the complexity of generating neuronal diversity in the brain and likely reflects the evolutionary origin of each LCN subtype that detects a highly specific visual feature and influence behaviors that might be specific to each species.

neuroscience↗

bioRxiv2024

CausalXtract: a flexible pipeline to extract causal effects from live-cell time-lapse imaging data

Live-cell microscopy routinely provides massive amount of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell-cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer associated fibroblasts directly inhibit cancer cell apoptosis, independently from anti-cancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.

systems biology↗

bioRxiv2024

High-throughput identification of the spatial origins of Drosophila optic lobe neurons using single-cell mRNA-sequencing

The medulla is the part of the Drosophila optic lobe with the greatest neuronal diversity, in which the identity of each neuronal type is specified in progenitors and newborn neurons via the integration of temporal, spatial, and Notch-driven patterning mechanisms. This identity is maintained in differentiating and adult neurons by the expression of neuronal type-specific combinations of terminal selectors, which are transcription factors expressed continuously during development and in the adult that are thought to control all neuronal type-specific gene expression. However, how the patterning mechanisms establish terminal selector expression is unknown. We have previously characterized the temporal and Notch origin of medulla neurons. Here we have used single-cell mRNA-sequencing to characterize their spatial origins and identified two new spatial subdomains. Together, this makes the medulla the first complex brain structure for which the patterning mechanisms specifying the identity of each neuronal type are known. This knowledge allowed us to identify correlations between patterning information, terminal selector expression and neuronal features. Our results suggest that different subsets of the patterning information accessible to a given neuronal type control the expression of each of its terminal selectors and of modules of terminal features, including neurotransmitter identity. Therefore, the evolution of new neuronal types could rely on the acquisition of modules of neuronal features pre-determined by their developmental origin.

developmental biology↗

bioRxiv2023

The nuclear basket regulates distribution and mobility of nuclear pore complexes in budding yeast

Nuclear pore complexes (NPCs) mediate all traffic between the nucleus and the cytoplasm and are among the most stable protein assemblies in cells. Budding yeast cells carry two variants of NPCs which differ in the presence or absence of the nuclear basket proteins Mlp1, Mlp2 and Pml39. The binding of these basket proteins occurs very late in NPC assembly and Mlp-positive NPCs are excluded from the region of the nuclear envelope that borders the nucleolus. Here, we use recombination-induced tag exchange (RITE) to investigate the stability of all the NPC subcomplexes within individual NPCs. We show that the nuclear basket proteins Mlp1, Mlp2 and Pml39 remain stably associated with NPCs through multiple cell-division cycles, and that Mlp1/2 are responsible for the exclusion of NPCs from the nucleolar territory. In addition, we demonstrate that binding of the FG-nucleoporins Nup1 and Nup2 depletes also Mlp-negative NPCs from this region by an independent pathway. We develop a method for single NPC tracking in budding yeast and observe that NPCs exhibit increased mobility in the absence of nuclear basket components. Our data suggest that the distribution of NPCs on the nucleus is governed by multiple interaction of nuclear basket proteins with the nuclear interior. Significance StatementO_LIA subset of yeast nuclear pore complexes have a basket structure at their nuclear face. The stoichiometry, architecture and molecular functions of the basket are not clear. C_LIO_LIThe authors use a tag exchange method to show stable binding of nuclear basket proteins through multiple generations. They also find that multiple nuclear basket proteins disfavour localization of NPCs proximal to the nucleolus. C_LIO_LIThese findings demonstrate that having a nuclear basket is a final and stable state for yeast NPCs. The methods developed can be applied to gain more insight into the properties of NPCs and other stable complexes as they age. C_LI

cell biology↗

bioRxiv2023

Spatial patterning regulates neuron numbers in the Drosophila visual system

Neurons must be made in the correct proportions to communicate with the appropriate synaptic partners and form functional circuits. In the Drosophila visual system, multiple subtypes of Distal medulla (Dm) inhibitory interneurons are made in distinct, reproducible numbers--from 5 to 800 per optic lobe. These neurons are born from a crescent-shaped neuroepithelium called the Outer Proliferation Center (OPC), which can be subdivided into specific domains based on transcription factor expression. We fate mapped Dm neurons and found that more abundant neural types are born from larger neuroepithelial subdomains, while less abundant subtypes are born from smaller ones. Additionally, morphogenetic Dpp/BMP signaling provides a second layer of patterning that subdivides the neuroepithelium into smaller domains to provide more granular control of cell proportions. Apoptosis appears to play a minor role in regulating Dm neuron abundance. This work describes an underappreciated mechanism for the regulation of neuronal stoichiometry.

developmental biology↗

bioRxiv2023

Subchronic alteration of vestibular hair cells in mice: implications for multisensory gaze stabilization

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.

neuroscience↗

bioRxiv2022

Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism

BackgroundThe trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards the definitive location of the parasite, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration. Methodology/Principal FindingsAn FhNEJ tegument protein extract (FhNEJ-Teg) was obtained in vitro, and its capability to bind the zymogen plasminogen (PLG) and enhance its conversion to the active protease, plasmin, were analyzed by a combination of enzyme-linked immunosorbent, chromogenic and immunofluorescence assays. Additionally, PLG-binding proteins in FhNEJ-Teg were identified by 2D electrophoresis coupled to mass-spectrometry analysis, and the interactions were validated using FhNEJ recombinant proteins. Conclusions/SignificanceOur results show that FhNEJ-Teg contains proteins that bind PLG and stimulate its activation to plasmin, which could facilitate the traversal of the intestinal wall by FhNEJ and contribute to the successful establishment of the parasite within its mammalian host. Altogether, our findings contribute to a better understanding of host-parasite relationships during early fasciolosis and may be exploited from a pharmacological and/or immunological perspective for the development of treatment and control strategies against this global disease. Author SummaryFasciolosis is a disease caused by parasites of the genus Fasciola, of which F. hepatica stands out as it has successfully spread all over the world and infects humans and animals throughout the entire global geography. Definitive hosts become infected by ingestion of aquatic plants or water contaminated with metacercariae, which excyst in the duodenum and release the so-called newly excysted juvenile flukes (FhNEJ). FhNEJ traverse the intestinal wall and evolve into immature parasites that migrate through the peritoneum and liver parenchyma until they reach their definitive location inside the major biliary ducts, where adult worms develop and egg shedding starts. In order to cross the intestinal wall, FhNEJ are endowed with a repertoire of proteases that degrade components of the intestinal extracellular matrix, and we hypothesized that they may also co-opt the proteolytic functions of plasmin, the central enzyme of the mammalian fibrinolytic system, to migrate more efficiently across host tissues. In this study, we demonstrate that FhNEJ express proteins on their tegument surface that interact with plasminogen, the zymogen of plasmin, and stimulate its conversion into its active form, which could potentially be used for trans-intestinal migration and contribute to the successful establishment of the parasite within its mammalian host.

molecular biology↗

bioRxiv2022

Unexpected higher convergence of human-great ape enteric viromes in central African forest than in a European zoo: A One Health analysis

Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this holistic study elucidates these processes, integrating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. Surprisingly, we find more enteric virome sharing between Cameroonian humans and great apes than in the zoo, a virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. In addition to physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens explain these unexpected findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing.

molecular biology↗