Biology subjects

Barbier, E.

Publications and source records attributed to Barbier, E..

13 recordsLinked to original sources

bioRxiv2026

Reduced Prefrontal PRDM2 Increases Stress-Induced Reinstatement Across Sexes via a dmPFC-Nucleus Accumbens Pathway

Stress is a major driver of relapse in alcohol use disorder (AUD), partly through stress-induced dysregulation of prefrontal cortex (PFC) circuits that govern executive control, craving regulation, and adaptive behavioral responses. Such dysfunction may be partly driven by epigenetic regulation of transcriptional programs that shape PFC responses to stress. Here, we investigated the role of the histone methyltransferase PRDM2 in stress-induced relapse to alcohol seeking. Analysis of postmortem human tissue showed that PRDM2 expression in the PFC was reduced in both men and women with AUD compared with control individuals. To examine the functional significance of this reduction in alcohol-related behaviors, we used viral-mediated knockdown of Prdm2 in the dorsomedial prefrontal cortex (dmPFC) of male and female rats. Prdm2 knockdown increased vulnerability to stress-induced reinstatement of alcohol seeking in both sexes, without altering pain sensitivity or being influenced by estrous cycle stage. To determine whether this effect was mediated through specific prefrontal output pathways, we selectively reduced Prdm2 expression in dmPFC neurons projecting to the nucleus accumbens (NAc). Projection-specific knockdown also increased stress-induced reinstatement of alcohol seeking in male and female rats in a shock intensity-dependent manner. Together, these findings suggest that reduced PRDM2 expression in the PFC contribute to stress-induced relapse-like behavior and identify the dmPFC-NAc projection as a circuit through which PRDM2 influences alcohol seeking.

neuroscience↗

bioRxiv2026

Network reorganization distinguishes vulnerability and resilience to observational fear

Individuals vary widely in their responses to stress and threat, with some developing persistent fear after adverse experiences while others remain resilient. Such variability also extends to social contexts, where individuals can acquire information about danger by observing others in distress through observational fear learning. The neural mechanisms underlying individual differences in responses to socially conveyed threat remain poorly understood. Here, we examined how variability in OFL relates to large-scale brain network organization. Rats observed conspecifics receiving tone-shock pairings and were later tested for fear responses to the conditioned stimulus. Behavioral analysis revealed two phenotypes: observational-susceptible rats displaying robust freezing and observational-resilient rats showing freezing levels comparable to controls. Despite these differences, both groups exhibited elevated corticosterone responses, indicating that socially conveyed threat was detected across animals. Brain-wide c-Fos mapping across 84 regions combined with graph-theoretical analysis revealed distinct network architectures associated with each phenotype. These findings suggest that susceptibility and resilience to socially acquired fear emerge from differences in distributed brain network organization.

neuroscience↗

bioRxiv2026

Structural basis of MfpD, a versatile pathogeny protein from the mfp conservon of Mycobacterium tuberculosis

The mfp conservon of Mycobacterium tuberculosis has been associated with fluoroquinolone resistance and encodes five conserved proteins, including the small GTPase MfpB and its regulatory partner MfpD. In this study, we combined phylogenetic, structural, and biophysical approaches to define the molecular basis of MfpD function. MfpD adopts a Roadblock/LC7-like /{beta} fold and forms a stable dimer in solution, with hydrophobic 2-helix interactions stabilizing the interface. Additional biophysical analyses and AlphaFold3 modeling suggest that MfpD may promote GTP hydrolysis by MfpB through a noncanonical Switch I-dependent mechanism. These findings establish the first structural framework for MfpD-MfpB interactions, building on previously identified in vitro catalytic properties and proposing new insights into MfpDs non-catalytic pathogenesis activity of MfpD in macrophages. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/709265v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@77b2d2org.highwire.dtl.DTLVardef@7d1908org.highwire.dtl.DTLVardef@f66eeforg.highwire.dtl.DTLVardef@ed159c_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

biochemistry↗

bioRxiv2025

Pangenome structure and ecological adaptation in the Klebsiella pneumoniae species complex: insights from a geographically and time limited multi-habitat study

Klebsiella pneumoniae species complex (KpSC) members inhabit distinct ecological habitats, yet the diversity and adaptation of environmental KpSC populations remain underexplored. We investigated KpSC transmission, pangenome structure and diversity, and functional gene enrichment across four distinct habitats in Burgundy, France over one year. In total, 664 environmental samples were collected from an organic vegetable farm (n=329), an organic cattle farm (n=304) and wastewater treatment plants (WWTP; n=31), alongside 47 clinical isolates. KpSC was detected in 22.4% of environmental samples, most commonly in WWTP (83.9%), followed by vegetable farm (27.1%) and cattle farm (11.2%). A total of 336 isolates were collected and whole-genome sequenced. K. pneumoniae sensu stricto (phylogroup Kp1) was predominant (76%), followed by K. variicola subsp. variicola (phylogroup Kp3) (21%). Genomic analyses revealed substantial novel diversity, especially in environmental habitats (67 novel STs), with limited cross transmission but clear local persistence. Over 90% of environmental isolates lacked acquired antimicrobial resistance genes, whereas half of the clinical isolates exhibited a multi-drug resistance profile. Comparative pangenome analyses showed Kp1 possessed a larger and more diverse pangenome than Kp3. Human-associated populations (clinical and WWTP) shared similar pangenome structures, although clinical isolates exhibited an expanded accessory genome. Cattle farm isolates had the most restricted and distinct pangenome while vegetable farm isolates displayed the largest total genomic repertoire. Functional enrichment analysis highlighted Kp3s environmental adaptation via conserved functions linked to the phylogroup genetic background, such as metabolic and regulatory pathways, including nitrogen fixation genes. Contrarily, human-associated populations, especially Kp1 members, were enriched in acquired functions linked to the ecological context, including antimicrobial and metal resistance determinants and mobile genetic elements. These findings emphasize phylogroup- and ecological niche-driven pangenome contrasts in KpSC, contributing to explain the successful adaptation of Kp1 to multiple habitats, including human-related settings.

genomics↗

bioRxiv2025

Ambecovirus, a novel Betacoronavirus subgenus circulating in neotropical bats sheds new light on bat-borne coronaviruses evolution

Understanding the viral diversity harboured by wildlife is essential for effective prediction and prevention of future zoonotic outbreaks. Bats, in particular, are recognized as natural reservoirs for several zoonotic viral pathogens of high impact on public health, including coronaviruses responsible for SARS, the rabies virus, Marburg, Ebola, Nipah and Hendra viruses. However, the large extent of bat viruses remains unexplored, especially in highly biodiverse regions of the Neotropics such as Brazil. We used a meta-transcriptomic to characterize new virus genomes found in blood, oral and anal samples collected from cave- and non-cave bats from Northeast Brazil. From a total of 19 coronavirus-positive bats, we have assembled two complete genomes of a new Betacoronavirus subgenus, named Ambecovirus (American betacoronavirus). The subgenus herein described is phylogenetically placed between the Sarbeco-/Hibeco-/Nebecovirus and the Merbeco-/Embecovirus clades, being basal to the former. While the conserved S2 region of the spike protein retained hallmark domains, including HR1 and HR2, the S1/S2 cleavage site and the furin cleavage site, the S1 region consistently displayed only the N-terminal domain. The receptor-binding domain could not be identified due to high dissimilarity relative to known congeneres. The detection of Ambercovirus in sympatric Pteronotus gymnonotus and Carollia perspicillata bats suggests interspecies transmission. Longitudinal sampling confirmed persistent Ambecovirus infection in P. gymnonotus over multiple years and virus dispersion at a minimum distance of 270 km between caves. The present study confirms that viral diversity in neotropical hosts remains largely unknown not just in Brazil but, likely, in the other countries of the region, supporting the need for a systematic approach to virome exploration and analysis followed by in vitro experimentation to assess zoonotic potential.

evolutionary biology↗

bioRxiv2024

High-resolution perfusion imaging in rodents using pCASL at 9.4 T

Adequate perfusion is critical for maintaining normal brain function and aberrations thereof are hallmarks of many diseases. Pseudo-Continuous Arterial Spin Labeling (pCASL) MRI enables noninvasive perfusion mapping without contrast agent injection and with higher signal-to-noise ratio (SNR) than alternative methods. Despite its great potential, pCASL remains challenging, unstable, and relatively low-resolution in rodents - especially in mice - thereby limiting the investigation of perfusion properties in many transgenic or other relevant rodent models of disease. Here, we address this gap by developing a novel experimental setup for high-resolution pCASL imaging in mice and combining it with the enhanced SNR of cryogenic probes. We show that our new experimental setup allows for optimal positioning of the carotids within the cryogenic coil, rendering labelling reproducible. With the proposed methodology, we managed to increase the spatial resolution of pCASL perfusion images by a factor of 15 in mice; a factor of 6 in rats is gained compared to the state of the art just by virtue of the cryogenic coil. We also show that the improved pCASL perfusion imaging allows much better delineation of specific brain areas, both in healthy animals as well as in rat and mouse models of stroke. Our results bode well for future high-definition pCASL perfusion imaging in rodents. Data availabilityData will be freely made available upon request.

neuroscience↗

bioRxiv2024

Triplex real-time PCR ZKIR-T assay for simultaneous detection of the Klebsiella pneumoniae species complex and identification of K. pneumoniae sensu stricto

Klebsiella pneumoniae species complex (KpSC) members, including the most important species K. pneumoniae (phylogroup Kp1 of the KpSC), are important opportunistic pathogens which display increasing rates of antimicrobial resistance worldwide. As they are widespread in food and the environment, there is a need for fast, sensitive and reliable methods to detect KpSC members in complex matrices. Previously, the ZKIR real-time PCR assay was developed to detect all KpSC members without distinction. Given that Kp1 is the clinically most significant phylogroup of the KpSC, here we aimed to simultaneously identify Kp1 while detecting all KpSC members. Three TaqMan probes were developed and used: the zkir P1 probe to detect phylogroups Kp1 to Kp5 and Kp7; the zkir P2 probe to detect phylogroup Kp6; and the Kp1 probe to specifically identify this phylogroup. The new assay was tested on a total of 95 KpSC and 19 non-KpSC strains from various sources, representing the different phylogroups as defined by whole genome sequencing. The results showed almost complete specificity, as the expected PCR results were obtained for 112 (98%) strains. The new triplex real-time PCR assay, called ZKIR-T, enables detection of all KpSC taxa while discriminating Kp1, which will be useful for rapid screening and to focus downstream analyses on chosen phylogroups of the KpSC. ImportanceThe pathogens of the Klebsiella pneumoniae species complex are widespread in food and animals and are amongst the main pathogens responsible for multidrug resistant infections in humans. In this study, we developed a highly sensitive detection assay that enables detection of this group of bacteria, with the simultaneous identification of the most common and clinically important species. This triplex one-reaction assay was shown to be highly sensitive and precise, enabling fast screening of varied samples for the presence of KpSC and K. pneumoniae sensu stricto.

microbiology↗

bioRxiv2022

The virome of bats inhabiting Brazilian biomes: knowledge gaps and biases towards zoonotic viruses

Bats are hosts of a large variety of viruses including some that may infect other vertebrates and humans. Research on bat-borne viruses attracted significant attention in recent years mainly due to epizootics caused by viruses having bats as hosts. The characterization of the viral communities of bats was then prioritized, but despite increasing efforts, there are large disparities in the geographical ranges covered and the methodologies employed around the world. As a result, large gaps remain in our current understanding of bat viromes and their role in disease emergence. This is particularly true for megadiverse regions in Latin America. This review aims to summarize the current understanding about bat-viruses that inhabit Brazilian biomes, one of the most bat species-rich and diverse regions of the globe. Taking into account all known bat-associated viral families studied in Brazilian biomes, we found that almost half of all bat species (86/181 species) were not investigated for viruses at all. Moreover, only a small fraction of viral lineages or families have been studied more in depth, usually employing targeted methods with limited power to characterize a broad virus diversity. Additionally, these studies relied on limited spatio-temporal sampling and small sample sizes. Therefore, our current understanding of bat viral communities in the Brazilian biomes is limited and biased at different levels, limiting zoonotic risk assessments of bat-borne viruses. Considering these limitations, we propose strategies to bridge the existing gaps in the near future.

microbiology↗

bioRxiv2022

Erbb4 deletion from fast-spiking interneurons causes psychosis-relevant neuroimaging phenotypes

Converging lines of evidence suggest that dysfunction of cortical parvalbumin-expressing (PV+) GABAergic interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and levels of glutamatergic metabolites, and decreases in binding of GABAA 5 receptors and the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between PV+ interneuron dysfunction and these neuroimaging readouts have yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal PV+ interneurons leads to several synaptic, behavioral and cognitive phenotypes relevant to psychosis in mice. Here, we investigated how this PV+ interneuron disruption affects the hippocampal in vivo neuroimaging readouts in the Erbb4 model. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n=12) and their wild-type littermates (Erbb4F/F, n=12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Erbb4 mutant mice showed significantly elevated CBF and glutamine levels, as well as decreased SV2A density compared to wild-type littermates. No significant GABAA receptor density differences were identified. These findings demonstrate that specific disruption of cortical PV+ interneurons in mice recapitulate some of the key neuroimaging findings in psychosis patients, and link PV+ interneuron deficits to non-invasive, translational measures of brain function and neurochemistry that can be used across species.

neuroscience↗

bioRxiv2022

Re-routing metabolism by the mitochondrial pyruvate carrier inhibitor MSDC-0160 attenuates neurodegeneration in a rat model of Parkinson's disease

BackgroundA growing body of evidence supports the idea that mitochondrial dysfunction might represent a key feature of Parkinsons disease (PD). Central regulators of energy production, mitochondria are also involved in several other essential functions such as cell death pathways and neuroinflammation which make them a potential therapeutic target for PD management. Interestingly, recent studies related to PD have reported a neuroprotective effect of targeting mitochondrial pyruvate carrier (MPC) by the insulin sensitizer MSDC-0160. As the sole point of entry of pyruvate into the mitochondrial matrix, MPC plays a crucial role in energetic metabolism which is impacted in PD. This study therefore aimed at providing insights into the mechanisms underlying the neuroprotective effect of MSDC-0160. MethodsWe investigated behavioral, cellular and metabolic impact of chronic MSDC-0160 treatment in unilateral 6-OHDA PD rats. We evaluated mitochondrial related processes through the expression of pivotal mitochondrial enzymes in dorsal striatal biopsies and the level of metabolites in serum samples using nuclear magnetic resonance spectroscopy (NMR)-based metabolomics. ResultsMSDC-0160 treatment in unilateral 6-OHDA rats improved motor behavior, decreased dopaminergic denervation and reduced mTOR activity and neuroinflammation. Concomitantly, MSDC-0160 administration strongly modified energy metabolism as revealed by increased ketogenesis, beta oxidation and glutamate oxidation to satisfy energy needs and maintain energy homeostasis. ConclusionMSDC-0160 exerts its neuroprotective effect through reorganization of multiple pathways connected to energy metabolism.

neuroscience↗

bioRxiv2021

High prevalence of Klebsiella pneumoniae in European food products: a multicentric study comparing culture and molecular detection methods

Klebsiella pneumoniae species complex (KpSC) is a leading cause of multidrug-resistant human infections. To better understand the potential contribution of food as a vehicle of KpSC, we conducted a multicentric study to define an optimal culture method for its recovery from food matrices, and to characterize food isolates phenotypically and genotypically. Chicken meat (n=160) and salad (n=145) samples were collected in five European countries and screened for KpSC presence using culture-based and ZKIR qPCR methods. Enrichment using buffered peptone water followed by streaking on Simmons citrate agar with inositol (44{degrees}C/48h) was defined as the most suitable selective culture method for KpSC recovery. High prevalence of KpSC was found in chicken meat (60% and 52% by ZKIR qPCR and culture approach, respectively) and salad (30% and 21%, respectively) samples. Genomic analyses revealed high genetic diversity with the dominance of phylogroups Kp1 (91%) and Kp3 (6%). 82% of isolates presented a natural antimicrobial susceptibility phenotype and genotype, with only four CTX-M-15-producing isolates detected. Notably, identical genotypes were found across samples: same food type and same country (15 cases); different food types and same country (1); same food type and two countries (1), suggesting high rates of transmission of KpSC within the food sector. Our study provides a novel isolation strategy for KpSC from food matrices and reinforces the view of food as a potential source of KpSC colonization in humans. ImportanceBacteria of the Klebsiella pneumoniae species complex (KpSC) are ubiquitous and K. pneumoniae (Kp) is a leading cause of antibiotic-resistant infections in humans and animals. Despite the urgent public health threat represented by Kp, there is a lack of knowledge on the contribution of food sources to colonization and subsequent infection in humans. This is partly due to the absence of standardized methods for characterizing KpSC presence in food matrices. Our multicentric study provides and implements a novel isolation strategy for KpSC from food matrices and shows that KpSC members are highly prevalent in salads and chicken meat, reinforcing the view of food as a potential source of KpSC colonization in humans. Despite the large genetic diversity and the low-levels of resistance detected, the occurrence of identical genotypes across samples suggests high rates of transmission of KpSC within the food sector, which need to be further explored to define possible control strategies.

microbiology↗

bioRxiv2021

Early diagnosis of Parkinson's disease: A cross-species biomarker

BackgroundCare management of Parkinsons disease (PD) patients currently remains symptomatic, especially because diagnosis relying on the expression of the cardinal motor symptoms is made too late. Detecting PD earlier therefore represents a key step for developing therapies able to delay or slow down its progression. MethodsWe investigated metabolic markers in three different animal models of PD, mimicking different phases of the disease assessed by behavioral and histological evaluation, and in 2 cohorts of de novo PD patients (n = 95). Serum and brain tissue samples were analyzed by nuclear magnetic resonance spectroscopy and data submitted to advanced multivariate statistics. ResultsOur translational strategy reveals common metabolic dysregulations in serum of the different animal models and PD patients. Some of them were mirrored in the tissue samples, possibly reflecting pathophysiological mechanisms associated with PD development. Interestingly, some metabolic dysregulations appeared before motor symptom emergence, and could represent early biomarkers of PD. Finally, we built a composite biomarker with a combination of 6 metabolites. This biomarker discriminated animals mimicking PD from controls, even from the first, non-motor signs and very interestingly, also discriminated PD patients from healthy subjects. ConclusionFrom our translational study which included three animal models and two PD patient cohorts, we propose a promising composite biomarker exhibiting a high level of predictivity for PD diagnosis in its early phase, before motor symptoms appearance. FundingsANR, DOPALCOMP, Institut National de la Sante et de la Recherche Medicale, Grenoble Alpes University.

pathology↗

bioRxiv2018

From: Benjamin LemassonParametric response mapping as a new MRI approach for the characterization of posttraumatic cerebral edema

PurposeCerebral edema is usually assessed with mean ADC value obtained with MRI. We aimed to use parametric response mapping (PRM), a voxel-based analysis, in a rat model of traumatic brain injury (TBI) to characterize the cerebral edema and to compare findings to those obtained with the classical global mean ADC analysis. Ultimately we wished to test whether early PRM analysis could identify the vasogenic or cellular edematous pattern two hours after trauma.\n\nMaterials and MethodsExperiments were conducted in a rat model of TBI in accordance with French Government guidelines. Eighteen traumatic brain-injured rats (TBI group) were compared to 7 sham-operated rats (Sham group). Diffusion-weighted images were acquired before and immediately (H0), 60min (H1) and 120min (H2) after the trauma. Two regions of interest (ROI) including cortex (cortical-ROI) and the whole brain (brain-ROI) were manually delineated.\n\nResultsAveraged ADC value in cortical-ROI was significantly reduced at H2 in the TBI group versus Sham group (715{+/-}24 vs 781{+/-}16 m2/sec; p=0.04), not in brain-ROI (748{+/-}27 vs 801{+/-}18 m2/sec; p=0.32). By contrast, PRM values were significantly changed in these two ROIs at as soon as H1 in the TBI group (27.5{+/-}4% of the voxels beyond the PRM threshold in TBI group vs 5.1{+/-}1% in sham group; p<0.01). PRM was able to identify the nature of post traumatic cerebral edema: vasogenic, cellular or mixed pattern. ADC data obtained immediately after TBI and analyzed using PRM correlated with ADC data obtained at H2.\n\nConclusionThe PRM approach is more sensitive than averaged ADC at detecting and identifying post-traumatic brain edema. It is able to PRM might be a promising tool to individualize the management of patients with posttraumatic brain edema.

neuroscience↗