Biology subjects

Dupont, S.

Publications and source records attributed to Dupont, S..

16 recordsLinked to original sources

bioRxiv2025

Tinnitus perception is linked to arousal system dysfunction

Tinnitus, the perception of sound in the absence of an external source, affects 14% of the population and is often associated with concentration and emotional difficulties. However, the characterization of the associated cognitive difficulties remains unclear. We hypothesize that attentional complaints are due to a dysfunction of the exogenous or endogenous orientation of attention, or of the arousal system. In this study, 200 participants (100 with chronic tinnitus and 100 matched controls) completed a battery of cognitive tasks assessing attention, alertness and executive functions, including the Attentional Network Task (ANT), Sustained Attention to Response Task (SART) with mind wandering evaluations, Stroop, and Trail Making Test. Tinnitus comorbidities, including hearing loss, sleep quality, anxiety, and hyperacusis were controlled. The results showed that individuals with tinnitus had a reduced sensitivity to alert signals, and lower sustained attention abilities, both suggesting lower levels of arousal. Mind-wandering analyses revealed fewer planning-related thoughts in the tinnitus group, suggesting higher needed cognitive resources to perform the task. Contrary to prior findings, we found no evidence of deficits in executive functioning specific to tinnitus; rather, executive impairments were associated with hearing loss and sleep disturbances. Overall, these findings support the hypothesis that tinnitus is linked to a dysfunction in the arousal system--likely involving the locus coeruleus-noradrenergic network. This work proposes a new theoretical framework implicating arousal dysregulation as a core mechanism in tinnitus-related cognitive complaints. Significance StatementTinnitus, the perception of sound without an external source, affects millions worldwide and is often accompanied by concentration difficulties. By rigorously controlling for hearing loss, sleep deprivation, and anxiety, we isolate the core cognitive changes linked to tinnitus itself. Our study reveals that attentional deficits in tinnitus primarily arise from dysregulation in the brains arousal system. We propose a novel integrative framework in which arousal system dysfunction underlies the cognitive and emotional symptoms associated with tinnitus, providing a new perspective for understanding the complex interactions between attention, sleep, and anxiety in this condition.

neuroscience↗

bioRxiv2025

Neutrophil extracellular traps block endogenous and intravenous thrombolysis-induced fibrinolysis in large vessel occlusion acute ischemic stroke

BackgroundIntravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is frequent but its causes remain elusive. Several non-exclusive mechanisms have been proposed to explain IVT failure, including failed delivery of tPA and inhibition of its activity. We investigated whether biologically relevant intrathrombus concentrations of t-PA were achieved in failed IVT in patients with LVO AIS, and whether neutrophil extracellular traps (NETs) contributed to IVT failure. MethodsIn this cohort study, a total of 205 thrombi from AIS patients with LVO were analyzed. 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additional subset of 69 AIS thrombi was used to decipher if and how NETs interfere with intrathrombus fibrinolysis. ResultsAIS thrombi from IVT patients contained more tPA than those from no-IVT patients (0.209 vs 0.093 {micro}g/mg of thrombus, p<0.0001). Plasminogen and tPA in AIS thrombi were found in association with fibrin and NETs. The ability of NETs to bind tPA and plasminogen, titrating them away from fibrin, was confirmed in a microfluidic model of thrombosis. While ex vivo addition of plasminogen did not cause lysis of either no-IVT or IVT thrombi, combining plasminogen with DNase 1 helped translate the increased tPA content of IVT thrombi into increased thrombolysis. We further show that DNase 1 enables tPA- and plasmin-mediated thrombolysis by eliminating fibrinolysis inhibitors from AIS thrombi. ConclusionsThese results indicate that intrathrombus tPA concentrations reached in failed IVT bear a therapeutic potential that is however impaired by NETs, which favor intrathrombus retention of fibrinolysis inhibitors and compete with fibrin for tPA and plasminogen binding. Our results stress the interest of DNase 1 to enhance the efficacy of current IVT tPA regimens. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIntravenous thrombolysis increases thrombus tPA content even when it fails to cause arterial recanalization in acute ischemic stroke C_LIO_LIThe fibrinolytic activity of intravenously-administered tPA is blocked by neutrophil extracellular traps in acute ischemic stroke thrombi C_LIO_LINeutrophil extracellular traps participate in thrombolysis resistance by retaining fibrinolysis inhibitors and titrating tPA and plasminogen away from fibrin in acute ischemic stroke thrombi C_LIO_LIDNase 1 can convert increased tPA content into increased fibrinolysis by eliminating NETs-associated fibrinolysis inhibitors in acute ischemic stroke thrombi C_LI 2) What are the clinical implications?O_LIDespite therapeutic failure, biologically significant intrathrombus tPA concentrations are achieved following intravenous thrombolysis at current tPA regimens C_LIO_LISequential administration of DNase 1 prior to intravenous thrombolysis could clear the way for tPA and potentiate its fibrinolytic activity for improved arterial recanalization efficacy C_LI

pathology↗

bioRxiv2024

Piezo1 is a mechanosensor of soft matrix viscoelasticity

Mechanosensitive ion channels have emerged as fundamental proteins in sensing extracellular matrix (ECM) mechanics. Among those, Piezo1 has been proposed as a key mechanosensor in cells. However, whether and how Piezo1 senses time-dependent ECM mechanical properties (i.e., viscoelasticity) remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line with adjustable Piezo1 expression with soft (400 Pa) and stiff (25 kPa) viscoelastic hydrogels with independently tuneable Youngs modulus and stress relaxation. We demonstrate that Piezo1 is a mechanosensor of viscoelasticity in soft ECMs, consistent with the molecular clutch model. By performing RNA sequencing (RNA-seq), we identified the transcriptomic phenotype of MSCs response to matrix viscoelasticity and Piezo1 activity, highlighting gene signatures that drive MSCs mechanobiology in soft and stiff viscoelastic hydrogels.

biophysics↗

bioRxiv2024

Waves of light at the bottom of the ocean: insights into the luminous systems of three Pennatuloidea (Anthozoa)

Bioluminescence is the production of visible light by living organisms. It occurs through the oxidation of a luciferin substrate catalysed by luciferase enzymes. Auxiliary proteins, such as fluorescent proteins and luciferin-binding proteins, can modify the light emitted wavelength or stabilize reactive luciferin molecules, respectively. Additionally, calcium ions are crucial for the luminescence across various species. Despite the large phylogenetic distribution of bioluminescent organisms, only a few systems have been comprehensively studied. Notably, cnidarian species of the Renilla genus utilize a coelenterazine-dependent luciferase, a calcium-dependent coelenterazine-binding protein and a green fluorescent protein. We investigated the bioluminescence of three sea pen species: Pennatula phosphorea, Anthoptilum murrayi and Funiculina quadrangularis (Pennatuloidea, Anthozoa). Their light-emission spectra reveal peaks at 510, 513 and 485 nm, respectively. A coelenterazine-based reaction was demonstrated in all three species. Using transcriptome analyses, we identified predicted transcripts coding for luciferases, green fluorescent proteins and coelenterazine-binding proteins for P. phosphorea and A. murrayi. Immunodetection confirmed the expression of luciferase in P. phosphorea and F. quadrangularis. We also expressed recombinant luciferase of A. murrayi, confirming its activity. We highlighted the role of calcium ions in bioluminescence, possibly associated with the mechanism of substrate release at the level of coelenterazine-binding proteins. The study proposes a model for anthozoan bioluminescence, offering new avenues for future ecological and functional research on these luminous organisms.

zoology↗

bioRxiv2024

Relationship between weapon size and six key behavioural and physiological traits in males of the European earwig

In many animals, male weapons are large and extravagant morphological structures that typically enhance fighting ability and reproductive success. It is generally assumed that growing and carrying large weapons is costly, thus only males in the best condition can afford it. In the European earwig, males carry weapons in the form of forceps-like cerci, which can vary widely in size within populations. While long forceps appear to increase males access to females, it is unknown whether it also correlates with other important male lifen-history traits. This information is important, however, in determining the potential reliability of forceps length as an indicator of male quality and the stability of this signalling system. Here, we tested whether forceps length is associated with six important behavioural and physiological traits in males of the European earwig. We sampled hundreds of males from two populations, selected 60 males with the longest and shortest forceps from each population, and then measured locomotor performance, boldness, aggregation behaviour, survival under harsh conditions, sperm storage, and survival after pathogen exposure. Contrary to our predictions, we detected no main association between forceps length and the traits measured. This lack of association was consistent between the two populations, although there were population-specific levels of boldness, aggregation and survival in harsh conditions (for long-forceps males only). Overall, these results challenge our current understanding of the function and quality signal of forceps length in this species and raise questions about the evolutionary drivers that could explain the maintenance of weapon size diversity within and between populations.

evolutionary biology↗

bioRxiv2023

The brittle star genome illuminates the genetic basis of animal appendage regeneration

Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here, we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star genome is the most rearranged amongst echinoderms sequenced to date, featuring a reorganised Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasise the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.

evolutionary biology↗

bioRxiv2023

Improving the annotation of the cattle genome by annotating transcription start sites in a diverse set of tissues and populations using CAGE sequencing

Understanding the genomic control of tissue-specific gene expression and regulation can help to inform the application of genomic technologies in farm animal breeding programmes. The fine mapping of promoters (transcription start sites [TSS]) and enhancers (divergent amplifying segments of the genome local to TSS) in different populations of cattle across a wide diversity of tissues provides information to locate and understand the genomic drivers of breed- and tissue-specific phenotypes. To this aim we used Cap Analysis Gene Expression (CAGE) sequencing to define TSS and their co-expressed short-range enhancers (<1kb) in the ARS-UCD1.2_Btau5.0.1Y reference genome (1000bulls run9) and analysed tissue- and population specificity of expressed promoters. We identified 51,295 TSS and 2,328 TSS-Enhancer regions shared across the three populations (Holstein, Charolais x Holstein and Kinsella beef composite [KC]). In addition, we performed a comparative analysis of our cattle dataset with available data for seven other species to identify TSS and TSS-Enhancers that are specific to cattle. The CAGE dataset will be combined with other transcriptomic information for the same tissues generated in the BovReg project to create a new high-resolution map of transcript diversity across tissues and populations in cattle. Here we provide the CAGE dataset and annotation tracks for TSS and TSS Enhancers in the cattle genome. This new annotation information will improve our understanding of the drivers of gene expression and regulation in cattle and help to inform the application of genomic technologies in breeding programmes.

genomics↗

bioRxiv2022

Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis

Mammalian sex is determined by opposing networks of ovarian and testicular genes that are well characterized. However, its epigenetic regulation is still largely unknown, thus limiting our understanding of a fundamental process for species propagation. Here we explore the 3D chromatin landscape of sex determination in vivo, by profiling FACS-sorted embryonic mouse gonadal populations, prior and after sex determination, in both sexes. We integrate Hi-C with ChIP-seq experiments using METALoci, a novel genome spatial auto-correlation analysis that identifies 3D enhancer hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination, affecting the enhancer hubs of hundreds of genes that display temporal- and sex-specific expression. Moreover, the identification of the 3D enhancer hubs allows the reconstruction of regulatory networks, revealing key transcription factors involved in sex determination. By combining predictive approaches and validations in transgenic mice we identify a novel Fgf9 regulatory hub, deletion of which results in male-to-female sex reversal with the upregulation of ovarian-specific markers and the initiation of meiosis. Thus, spatial auto-correlation analysis is an effective strategy to identify regulatory networks associated to biological processes and to further characterize the functional role of the 3D genome.

developmental biology↗

bioRxiv2022

Measuring brain critical dynamics to inform Brain-Computer Interfaces

Large-scale interactions among multiple brain regions manifest as bursts of activations called neuronal avalanches, which reconfigure according to the task at hand and, hence, might constitute natural candidates to design brain-computer interfaces (BCI). To test this hypothesis, we used source-reconstructed magneto/electroencephalography, during resting state and a motor imagery task performed within a BCI protocol. To track the probability that an avalanche would spread across any two regions we built an avalanche transition matrix (ATM) and demonstrated that the edges whose transition probabilities significantly differed between conditions hinged selectively on premotor regions in all subjects. Furthermore, we showed that the topology of the ATMs allows task-decoding above the current gold standard. Hence, our results suggest that Neuronal Avalanches might capture interpretable differences between tasks that can be used to inform brain-computer interfaces.

neuroscience↗

bioRxiv2021

Direct and latent effects of ocean acidification on the transition of a sea urchin from planktonic larva to benthic juvenile

AO_SCPLOWBSTRACTC_SCPLOWOngoing ocean acidification (OA) is expected to affect marine organisms and ecosystems. While sea urchins can survive a wide range of pH, this comes at a high energetic cost, and early life stages are particularly vulnerable. Information on how OA affects transitions between life-history stages is scarce. We evaluated the direct and indirect effects of pH (pHT 8.0, 7.6 and 7.2) on the development and transition between life-history stages of the sea urchin Strongylocentrotus droebachiensis, from fertilization to early juvenile. Continuous exposure to low pH negatively affected larval mortality and growth. At pH 7.2, formation of the rudiment (the primordial juvenile) was delayed by two days. Larvae raised at pH 8.0 and transferred to 7.2 after competency had mortality rates five to six times lower than those kept at 8.0, indicating that pH also has a direct effect on older, competent larvae. Latent effects were visible on the larvae raised at pH 7.6: they were more successful in settling (45%) and metamorphosing (30%) than larvae raised at 8.0 (17 and 1% respectively). These direct and indirect effects of OA on settlement and metamorphosis have important implications for population survival.

developmental biology↗

bioRxiv2021

Temperature shapes oviposition site selection and post-oviposition egg transport in an insect with parental care

AO_SCPLOWBSTRACTC_SCPLOWDepositing eggs in an area with adequate temperature is often crucial for mothers and their offspring, as the eggs are immobile and therefore cannot avoid exposure to sub-optimal temperatures. However, the importance of temperature on oviposition site selection is less clear when mothers can avoid these potential adverse effects by both moving their eggs after oviposition and providing other forms of egg care. In this study, we addressed this question in the European earwig, an insect in which mothers care for the eggs during several months in winter, frequently moving them during this period. We set up 60 females from two random natural populations (as this species often exhibits population-specific life-history traits and behaviours) under controlled thermal gradients, and recorded the temperature at which they built their nests, tested whether they moved their eggs after an experimental temperature change, and measured the effects on egg development and hatching rate. Our results demonstrate that females indeed select oviposition sites according to temperature, and can move their eggs to reach warmer temperatures. We also show that these warmer temperatures are necessary to ensure egg hatching. Although this set of behavioural thermoregulations is present in the two tested populations, we found a population-specific modality of expression. These included the range of temperatures explored before oviposition, temperature selected at oviposition and dynamics of egg transport following a temperature change. Overall, our study sheds light on a new post-oviposition strategy in female insects that overwinter with their eggs for coping with temperature changes. More generally, it also reveals that egg care and/or egg transport do not prevent behavioural thermoregulation via oviposition site selection and highlights the diversity of behaviours that insects can adopt to enhance their tolerance to global climate change.

evolutionary biology↗

bioRxiv2020

Fascin1 empowers YAP mechanotransduction and promotes cholangiocarcinoma development

Mechanical forces control cell behavior, including cancer progression. Cells sense forces through actomyosin and YAP, but what regulators of actin mechanotransduction play relevant roles in vivo remains unclear. Here we identify the Fascin1 F-actin bundling protein as a key factor sustaining YAP activation in response to ECM mechanical cues. This is relevant in the mouse liver, where Fascin1 regulates YAP-dependent hepatocyte dedifferentiation. Moreover, Fascin1 is required in the AKT/NICD system and sufficient together with AKT to induce cholangiocarcinomas in mice, recapitulating genetic YAP requirements, and its expression in intrahepatic cholangiocarcinomas correlates with aggressiveness and poor patient prognosis. We propose that Fascin1 represents a pro-oncogenic mechanism that can be exploited during intrahepatic cholangiocarcinoma development to overcome a mechanical tumor-suppressive environment.

cancer biology↗

bioRxiv2020

EphB6 regulates TFEB-lysosomal pathway and survival of disseminated indolent breast cancer cells

Late relapse of disseminated cancer cells is a common feature of some types of tumors. Several intrinsic and extrinsic factors have been shown to affect reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes persistence of DDCCs from estrogen receptor positive (ER+) breast tumors. Here we show that TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct contact of DDCCs with alveolar type I-like lung epithelial cells drives lysosomal accumulation and EphB6 induction. EphB6 contributes to TFEB transcriptional activity and lysosome formation in DDCCs in vitro and in vivo, and supports survival of DDCCs in coculture and in vivo. Furthermore, signaling from EphB6 promotes the proliferative response of surrounding lung parenchymal cells in vivo.

cancer biology↗

bioRxiv2020

Alteration of gut microbiota with rifampicin does not impair maternal care in the European earwig

AO_SCPLOWBSTRACTC_SCPLOWThe microbes residing within the gut of an animal host often increase their own fitness by modifying their hosts physiological, reproductive, and behavioural functions. Whereas recent studies suggest that they may also shape host sociality and therefore have critical effects on animal social evolution, the impact of the gut microbiota on maternal care remains unexplored. This is surprising, as this behaviour is widespread among animals, often determines the fitness of both juveniles and parents, and is essential in the evolution of complex animal societies. Here, we tested whether life-long alterations of the gut microbiota with rifampicin - a broad-spectrum antibiotic - impair pre- and post-hatching maternal care in the European earwig. Our results first confirm that rifampicin altered the mothers gut microbial communities and indicate that the composition of the gut microbiota differs before and after egg care. Contrary to our predictions, however, the rifampicin-induced alterations of the gut microbiota did not modify pre- or post-hatching care. Independent of maternal care, rifampicin increased the females feces production and resulted in lighter eggs and juveniles. By contrast, rifampicin altered none of the other 21 physiological, reproductive and longevity traits measured over the 300 days of a females lifetime. Overall, these findings reveal that altering the gut microbiota with a large spectrum antibiotic such as rifampicin does not necessarily affect host sociality. They also emphasize that not all animals have evolved a co-dependence with their microbiota and call for caution when generalizing the central role of gut microbes in host biology.

evolutionary biology↗

bioRxiv2018

Spatiotemporal neural correlates of brain-computer interface learning

Brain-computer interfaces have been largely developed to allow communication, control, and neurofeedback in human beings. Despite their great potential, BCIs perform inconsistently across individuals. Moreover, the neural processes activated by training that enable humans to achieve good control remain poorly understood. In this study, we show that BCI skill acquisition is paralleled by a progressive reinforcement of task-related activity and by the reduction of connectivity between regions beyond those primarily targeted during the experiments. Notably, these patterns of activity and connectivity reflect growing automaticity and predict future BCI performance. Altogether, our findings provide new insights in the neural mechanisms underlying BCI learning, which have implications for the use of this technology in a broad range of real-life applications.

neuroscience↗

bioRxiv2018

Biogeography masks diet-induced shifts in the bacterial community associated with larvae of the sea urchin Strongylocentrotus droebachiensis

Animals acclimate to changes in their environment through diverse responses, including phenotypic plasticity and shifts in their microbiome. These microbial communities are also taxonomically distinct across the geographical distribution of the host. It is less known, however, whether taxonomic differences in host-associated bacterial communities between geographically distinct populations mask shifts due to environmental changes within a population. We tested for potential ecological masking using larvae of the echinoid Strongylocentrotus droebachiensis from three coastal locations in the Pacific and Atlantic Oceans that were exposed to four feeding regimes. When considering OTU membership and the relative proportion of those taxa, the composition of the larval-associated bacterial communities were best explained by location, not feeding regime. Similarly, predicted metagenomic gene profiles from these bacterial communities were congruent with population specificity and may suggest a role in metabolism. We hypothesize that, while much of the differences in the bacterial communities is related to the large geographic distances between these locations, the predicted overlapping functions of the microbiome may relate to responding to ecological variation experienced by these larvae. Taken together, these results suggest that differences in community composition between populations masks local variation, and that scaling should be considered in when studying microbiome dynamics.

ecology↗