Biology subjects

Roussel, P.

Publications and source records attributed to Roussel, P..

6 recordsLinked to original sources

bioRxiv2025

Nucleolar Targeting and ROS-dependent inhibition of rRNA synthesis by Epstein-Barr Virus Nuclear Antigen 1

Epstein-Barr virus nuclear antigen 1 (EBNA-1) is essential for viral episome maintenance and is consistently expressed in all forms of EBV latency. In a previous study, we observed EBNA-1 localizing in the nucleolus, as well as its interaction with the nucleolar protein EBP2 in both the nucleoplasm and nucleoli. Nucleoli are dynamic nuclear domains that coordinate ribosome assembly with the regulation of cell cycle progression and stress responses. Here, we studied the mechanism by which EBNA-1 achieves nucleolar localization and functional consequences for host cell physiology. We observed that EBNA-1 nucleolar accumulation occurs specifically during late G1 and S phase and depends on a bipartite nucleolar localization signal (NoLS) composed of two cooperative Weber motifs separated by 24 amino acids. Mutations disrupting NoLS abolish interaction with the nucleolar protein EBP2, whose depletion similarly prevents EBNA-1 nucleolar import. Once in the nucleolus, EBNA1 triggers a 50 % reduction in the synthesis of ribosomal RNA (rRNA) which leads to a global reduction in cellular protein production. In addition, EBNA1 nucleolar targeting induces reactive oxygen species (ROS) production and antioxidant treatment restores both rRNA transcription and protein synthesis. These findings identify EBP2 as a viral nucleolar docking partner and establish nucleolar targeting of EBNA1 as a regulated, cell cycle-dependent process that links oxidative stress to the perturbation of ribosome biogenesis. This mechanism may contribute to EBNA1s ability to promote cell survival and transformation. IMPORTANCEEBNA1 is the only Epstein-Barr virus protein that is consistently expressed in all forms of latency and in every EBV-associated tumor. Although it localizes to the nucleolus and interacts with three nucleolar proteins, its influence on nucleolar functions had never been investigated. Here, we demonstrate that EBNA1s nucleolar targeting is a strictly cell-cycle-regulated process that depends on a previously unrecognized bipartite nucleolar localization signal as well as its interaction with the nucleolar protein EBP2. Once inside the nucleolus, EBNA1 induces a ROS-dependent suppression of rRNA synthesis, resulting in a global decrease in cellular protein production. In addition, these findings uncover a new function of EBNA1: the ability to induce nucleolar stress without activating canonical apoptotic pathways, thereby promoting host-cell survival and potentially contributing to EBV-driven oncogenesis

microbiology↗

bioRxiv2025

In vivo autofluorescence lifetime imaging of the Drosophila brain captures metabolic shifts associated with memory formation

Neuronal energy regulation is increasingly recognized as a critical factor underlying brain functions and their pathological alterations, yet the metabolic dynamics that accompany cognitive processes remain poorly understood. As a label-free and minimally invasive technique, fluorescence lifetime imaging (FLIM) of coenzymes NADH and NADPH (collectively referred to as NAD(P)H) offers the possibility to resolve cellular metabolic profiles with high spatial precision. However, NAD(P)H FLIMs capacity to detect subtle variations in neuronal metabolism has not been demonstrated. In this study, we applied NAD(P)H FLIM to map the metabolic profiles of Drosophila neurons in vivo across multiple scales, focusing on the primary centers for associative memory: the mushroom bodies (MBs). At a broad scale, we obtained an overview of the metabolic signatures of the main brain tissue and identified a marked difference between neuropil and cortex areas. At a finer scale, our findings revealed notable heterogeneity in the basal metabolic profiles of distinct MB neuron subtypes. Measurements performed after associative olfactory learning also uncovered a low-magnitude subtype-specific metabolic shift associated with memory formation, suggesting the utility of NAD(P)H FLIM in detecting physiology-driven changes linked to brain function. These results establish a promising framework for studying the spatial heterogeneities and the dynamics of cerebral energy metabolism in vivo.

neuroscience↗

bioRxiv2024

Evidence for common spike-based temporal coding of overt and covert speech in pars triangularis of human Broca's area

Brocas area has long been described as a central region of cortical speech networks. Yet, its detailed role during speech production remains largely unknown and even sometimes debated. Recordings at the individual neuron level could help understand whether and how speech is encoded in this region but such data remain very scarce. Here we use direct intracortical recording in pars triangularis of human Brocas area to show that the encoding of speech in this region relies not only on spike rates but also on the precise timing of action potentials within individual spike trains. First, we found that the overall spike rate of the whole population remained unchanged between periods of rest, overt and covert speech, but that individual firing rates of a few neurons fluctuated across these conditions. These fluctuations resulted in different overall population dynamics across conditions. Next, we also observed that the temporal arrangement of spikes within individual spike trains was not purely random but also signed which sentence was produced. By matching ensemble spike trains based on inter-spike intervals, it was possible to decode which sentence had been pronounced well above chance and with a comparable accuracy than when using spike counts. Moreover, the temporal code characterizing the overt production of individual sentences was found to be largely conserved when the same sentences were covertly imagined and enabled to decode cover sentences with an accuracy 75% higher than when considering spike counts. Altogether, these results suggest the existence of 2 modes of speech encoding in Brocas area, one based on the modulation of individual firing rates and the other based on the precise temporal structure of individual spike trains, and that the latter type of encoding remains more largely conserved between overt and covert speech production.

neuroscience↗

bioRxiv2022

MHC-II expressing neutrophils circulate in blood and milk during mastitis and show high microbicidal activity

Bovine mastitis are mainly caused by bacterial infection. They are responsible for economic losses and have an impact on the health and welfare of animals. The increase in the somatic cell count in milk during mastitis is mainly due to the influx of neutrophils which have a crucial role in the elimination of pathogens. For a long time, these first line defenders has been view as microbes killers with limited role in the orchestration of the immune response. However, their role is more complex and we recently characterized a MHC-II expressing neutrophil subset with regulatory capacities in cattle. In this study, we questioned the implication of different neutrophils subsets in the mammary gland immunity during clinical and subclinical mastitis. Here, we described for the first time that, in blood as in milk, neutrophils are a heterogeneous population and encompass at least two subsets distinguishable with their expression of MHC-II. We observed higher bactericidal capacities of milk MHC-IIpos neutrophils as compared to their classical counterparts, due to a higher production of ROS and phagocytosis ability. MHC-IIpos neutrophils are enriched in milk during a subclinical mastitis as compared to blood. Moreover, we observed a positive and highly significant correlation between MHC-IIpos neutrophils and T lymphocytes present in milk during subclinical mastitis. To conclude, our study could open the way to the discovery of new biomarkers of mastitis inflammation.

immunology↗

bioRxiv2019

Acoustic contamination of electrophysiological brain signals during speech production and sound perception

A current challenge of neurotechnologies is the development of speech brain-computer interfaces to restore communication in people unable to speak. To achieve a proof of concept of such system, neural activity of patients implanted for clinical reasons can be recorded while they speak. Using such simultaneously recorded audio and neural data, decoders can be built to predict speech features using features extracted from brain signals. A typical neural feature is the spectral power of field potentials in the high-gamma frequency band (between 70 and 200 Hz), a range that happens to overlap the fundamental frequency of speech. Here, we analyzed human electrocorticographic (ECoG) and intracortical recordings during speech production and perception as well as rat microelectrocorticographic ({micro}-ECoG) recordings during sound perception. We observed that electrophysiological signals, recorded with different recording setups, often contain spectrotemporal features highly correlated with those of the sound, especially within the high-gamma band. The characteristics of these correlated spectrotemporal features support a contamination of electrophysiological recordings by sound. In a recording showing high contamination, using neural features within the high-gamma frequency band dramatically increased the performance of linear decoding of acoustic speech features, while such improvement was very limited for another recording showing weak contamination. Further analysis and in vitro replication suggest that the contamination is caused by a mechanical action of the sound waves onto the cables and connectors along the recording chain, transforming sound vibrations into an undesired electrical noise that contaminates the biopotential measurements. This study does not question the existence of relevant physiological neural information underlying speech production or sound perception in the high-gamma frequency band, but alerts on the fact that care should be taken to evaluate and eliminate any possible acoustic contamination of neural signals in order to investigate the cortical dynamics of these processes.

neuroscience↗

bioRxiv2019

Understanding the dynamics of physical activity practice in the health context through Regulatory Focus and Self-Determination theories

This research aimed to associate for the first time in the literature the Regulatory Focus and Self-Determination theories to understand the dynamics of physical activity practice in the health context. Two cross-sectional studies were conducted with 603 (Study 1) and 395 (Study 2) French volunteer participants aged from 18 to 69 and 19 to 71 respectively, and healthy or concerned by a health condition. The main results of structural equation modeling analyses demonstrated that across the two studies, health promotion focus was positively associated with intrinsic motivation (.44 < {beta} < .74, p < .001), integrated regulation (.47 < {beta} < .72, p < .001), identified regulation (.40 < {beta} < .69, p < .001) and introjected regulation (.41 < {beta} < .53, p < .001), whereas health prevention focus was positively related with external regulation (.31 < {beta} < .45, p < .001) and amotivation (.32 < {beta} < .38, p < .001). Bootstrapping analyses main results in Study 2 showed that health promotion focus was indirectly associated with physical activity through intrinsic motivation (95% CI [.02 to .11]), integrated regulation (95% CI [.00 to .08]), identified regulation (95% CI [.00 to .09]) and introjected regulation (95% CI [.04 to .12]), whereas health prevention focus was indirectly associated with physical activity through external regulation (95% CI [.00 to .12]). These studies reveal meaningful associations between Regulatory Focus and Self-Determination theories variables which support the relevance of associating these two models to understand the processes underlying the physical activity practice.

epidemiology↗