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Becker, Y.

Publications and source records attributed to Becker, Y..

5 recordsLinked to original sources

Cortical vestibular-evoked potentials depend on body orientation

Otolithic vestibular receptors encode linear acceleration and head orientation relative to gravity, providing a fundamental reference signal for perception, action, and higher-order cognitive functions. However, the cerebral dynamics of otolithic information processing and their sensitivity to body orientation remain poorly characterized. Here, we used sound-induced vestibular stimulation combined with electroencephalography (EEG) in human participants to characterize vestibular-evoked potentials (vEPs) and to examine how body orientation relative to gravity modulates these responses. Otolithic activation was validated using cervical vestibular-evoked myogenic potentials, confirming activation of otolithic pathways by 105 dB and 500 Hz tone pips. Acoustic stimuli included a novel masked stimulus that reduced auditory perception while preserving vestibular activation. Sound-induced vestibular stimulation elicited reliable short- and middle-latency vEP components. Importantly, middle-latency components Na/Pa (peak latency: 20-30 ms) and N*/P* (41-54 ms) were modulated by body orientation, showing reduced amplitudes in the supine compared with the upright position, but only for otolithic-activating sounds and not for matched auditory control stimuli. This orientation-dependent modulation was stronger for Na/Pa and was specific to otolithic-activating sounds, supporting a vestibular rather than auditory origin and highlighting early integration processes. This pattern suggests that modulation of vEPs primarily reflects context-dependent cerebral processing of otolithic signals rather than peripheral sensory mechanisms. Together, our results establish Na/Pa and N*/P* as reliable cerebral markers of otolithic processing and demonstrate that early cerebral vestibular responses are dynamically shaped by body orientation and postural context. NEW & NOTEWORTHYThis study identifies middle-latency vestibular-evoked potentials as reliable cerebral markers of otolithic information processing. We show that both Na/Pa and N*/P* are selectively modulated by body orientation for otolithic-activating sounds, but not for auditory controls. These findings reveal that early otolithic vestibular processing dynamically depends on bodily context, extending current models of multisensory vestibular integration.

neuroscience↗

Heparanase 2 regulates endothelial permeability and prevents from proteinuria via VEGFA and FGF signaling

BackgroundHeparan sulfates (HS) attached to the apical surface of vascular endothelial cells (ECs) play an important role in regulating endothelial permeability and ligand recognition by cell-surface receptors. Shedding of heparan sulfate (HS) from the EC surface increases vascular leakage and is associated with vascular diseases. Recently, heparanase 2 (Hpa2) was described as a novel regulatory molecule that controls HS shedding. However, its role in regulating HS physiology in the vascular endothelium is largely unknown. Here, we characterize the role of endogenous Hpa2 in the vertebrate vascular system. MethodsWe use zebrafish larvae as our primary animal model. Hpa2 expression and localization was examined by in situ hybridization and immunofluorescence. Hpa2 loss-of-function (LOF) was induced by CRISPR-Cas9 or morpholino antisense strategies. We assessed vascular permeability, blood vessel architecture, and EC morphology using transgenic zebrafish and transmission electron microscopy. EC expression profiles and HS quantity were analyzed in Hpa2-LOF larvae. The capacity of recombinant Hpa2 to modulate signaling in ECs by the HS-binding growth factors fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A165 (VEGFA165) was tested by western blotting and immunofluorescence. Attenuation of the Hpa2-LOF phenotype was tested in vivo in zebrafish larvae via use of recombinant Hpa2 and pharmacological inhibition of FGF and VEGFA signaling. ResultsWe detected hpse2 expression in hepatic tissue and localized the protein in blood vessels. Hpa2-LOF larvae exhibited increased vascular permeability, occasional hypersprouting, and altered EC and extracellular matrix (ECM) morphology. Hpa2-LOF also reduced HS levels and caused changes in the endothelial transcriptome characterized by dysregulated genes involved in ECM-receptor interaction and signal transduction regulation. Recombinant hHpa2 rescued the Hpa2-LOF phenotype in zebrafish. We showed in vitro that Hpa2 competes with FGF2 and VEGFA165 for binding on the EC surface and consequently reduces the cellular response these factors elicit. Pharmacological inhibition of these pathways alleviated the Hpa2-LOF phenotype in zebrafish. ConclusionWe conclude that Hpa2 is a circulating molecule that maintains vascular integrity by regulating HS-dependent processes on the EC surface. These results may translate into novel strategies applying recombinant Hpa2 to treat microvascular diseases.

physiology↗

Planum Temporale grey matter volume asymmetries in new-born monkeys (Papio anubis)

The Planum Temporale (PT) is one of the key hubs of the language network in the human brain. The gross asymmetry of this perisylvian region toward the left brain was considered as the most emblematic marker of hemispheric specialization of language processes in the brain. Interestingly, this neuroanatomical signature was documented also in newborn infants and preterms, suggesting the early brains readiness for language acquisition. Nevertheless, this latter interpretation was questioned by a recent report in nonhuman primates of a potential similar signature in newborn baboons Papio anubis based on PT surface measures. Whether this "tip of the iceberg" PT asymmetry is actually reflecting asymmetry of its underlying grey matter volume remain unclear but critical to investigate potential continuities of cortical specialization with human infants. Here we report a population-level leftward asymmetry of the Planum Temporale grey matter volume in in vivo 34 newborn baboons Papio anubis, which showed intra-individual positive correlation with PT surfaces asymmetry measures but also a more pronounced degree of leftward asymmetry at the population-level. This finding demonstrates that PT leftward structural asymmetry in this Old World monkey species is a robust phenomenon in early primate development, which clearly speaks for a continuity with early human brain specialization. Results also strengthen the hypothesis that early PT asymmetry might be not a human-specific marker for the pre-wired language-ready brain in infants.

neuroscience↗

On the Gestural Origin of Language Lateralisation: Manual Communication reflects Broca's Asymmetry in Monkeys

Manual gestures and speech recruit a common neural network, involving Brocas area in the left hemisphere. Such speech-gesture integration gave rise to theories on the critical role of manual gesturing in the origin of language. Within this evolutionary framework, research on gestural communication in our closer primate relatives has received renewed attention for investigating its potential language-like features. Here, using in-vivo anatomical MRI in 50 baboons, we found that communicative gesturing is related to Broca homologues marker in monkeys, namely the ventral portion of the Inferior Arcuate sulcus (IA sulcus). In fact, both direction and degree of gestural communications handedness - but not handedness for object manipulation - are associated and correlated with contralateral depth asymmetry at this exact IA sulcus portion. In other words, baboons that prefer to communicate with their right hand have a deeper left-than-right IA sulcus, than those preferring to communicate with their left hand and vice versa. Interestingly, in contrast to handedness for object manipulation, gestural communications lateralisation is not associated to the Central sulcus depth asymmetry, suggesting a double dissociation of handedness types between manipulative action and gestural communication. It is thus not excluded that this specific gestural lateralisation signature within the baboons frontal cortex might reflect a phylogenetical continuity with language-related Broca lateralisation in humans.

neuroscience↗

Analysis of Epichloë festucae small secreted proteins in the interaction with Lolium perenne

Epichloe festucae is an endophyte of the agriculturally important perennial ryegrass. This species systemically colonises the aerial tissues of this host where its growth is tightly regulated thereby maintaining a mutualistic symbiotic interaction. Recent studies have suggested that small secreted proteins, termed effectors, play a vital role in the suppression of host defence responses. To date only a few effectors with important roles in mutualistic interactions have been described. Here we make use of the fully assembled E. festucae genome and EffectorP to generate a suite of 141 effector candidates. These were analysed with respect to their genome location and expression profiles in planta and in several symbiosis-defective mutants. We found an association between effector candidates and a class of transposable elements known as MITEs, but no correlation with other dynamic features of the E. festucae genome, such as transposable element-rich regions. Three effector candidates and a small GPI-anchored protein were chosen for functional analysis based on their high expression in planta compared to in culture and their differential regulation in symbiosis defective E. festucae mutants. All three candidate effector proteins were shown to possess a functional signal peptide and two could be detected in the extracellular medium by western blotting. Localization of the effector candidates in planta suggests that they are not translocated into the plant cell, but rather, are localized in the apoplastic space or are attached to the cell wall. Deletion and overexpression of the effector candidates, as well as the putative GPI-anchored protein, did not affect the plant growth phenotype or restrict growth of E. festucae mutants in planta. These results indicate that these proteins are either not required for the interaction at the observed life stages or that there is redundancy between effectors expressed by E. festucae.

genetics↗