Biology subjects

Leu, C.

Publications and source records attributed to Leu, C..

6 recordsLinked to original sources

bioRxiv2026

Posterior insula oscillations are not modulated by changes in perceived intensity: Evidence from human intracerebral EEG

The human insular cortex is involved in a multitude of processes essential for survival, but its precise role in pain perception remains debated. While it has been shown that ongoing oscillatory activity in the posterior insula is preferentially modulated by thermonociceptive input, it is unclear whether these modulations are functionally related to changes in pain perception. To assess this link, neural responses to sustained periodic thermonociceptive and non-nociceptive vibrotactile stimulation delivered at a frequency of 0.2 Hz were measured using intracerebral electrode contacts located in the anterior (n=63) and posterior (n=37) insular cortices of 10 patients undergoing presurgical evaluation for focal epilepsy. An arithmetic task was employed concomitant to the stimulation, aiming to reduce participants perceived intensity while leaving the physical stimulation parameters unchanged. A frequency-tagging analysis approach was used to assess the modulation of the ongoing neural oscillations. As expected, the perception of the stimulation was significantly reduced during the arithmetic task to a similar extent in both modalities. Yet, no congruent reduction in the frequency-tagged oscillatory responses was found in the posterior insula during distraction, for either of the modalities. On the contrary, during distraction, vibrotactile stimulation elicited larger responses in the anterior insula. These findings suggest that top-down modulation via distraction differentially affects anterior insula responses to innocuous vibrotactile input, while thermonociceptive processing appears to involve additional neural systems during distraction that are not equivalently engaged by vibrotactile stimulation.

neuroscience↗

bioRxiv2025

Conserved and Lineage-Specific Roles of KEA-Mediated Ion Homeostasis in Chlamydomonas

In Arabidopsis thaliana, seamless plastid gene expression and development depend on finely balanced ion homeostasis across the inner envelope (IE) membrane, maintained by the K/H antiporters AtKEA1/2. To assess whether these functions are retained across mono- and polyplastidic representatives of the green lineage, we studied CrKEA1, the sole IE KEA homolog in the unicellular alga Chlamydomonas reinhardtii. Using CRISPR/Cas9, we generated a Cr-kea1 knockout mutant that exhibits impaired photoautotrophic growth, chloroplast deformation, and photoinhibition. Transcriptomics revealed strong induction of ribosome biogenesis genes and reduced abundance of transcripts associated with cell and plastid division. Further RNA analyses confirmed defects in stromal rRNA maturation of Cr-kea1, paralleling observations from Arabidopsis kea1kea2 mutants. Expression of CrKEA1 in Arabidopsis rescued growth and rRNA maturation in At-kea1kea2, demonstrating functional continuity after the ancient divergence between the two lineages. Cross-species transcriptomic comparisons further revealed that IE KEA loss elicits both shared and species-specific transcriptional responses: PhANG repression was conserved between algae and plants, whereas activation of the chloroplast unfolded protein response (cpUPR) and reduced expression of genes tied to cell-cycle and plastid fission occurred only in Chlamydomonas. Single-cell time-lapse imaging confirmed that Cr-kea1 exhibits an increased frequency of aberrant cytokinesis, unequal division, and division failure. Our findings demonstrate that while IE KEA transporters fulfill conserved roles in maintaining the conditions for plastid gene expression, their integration into broader cellular networks has diverged between unicellular chlorophytes and embryophytes (land plants). This underscores a lineage-dependent tuning of plastid-nucleus communication shaped by organismal complexity and plastid number. One-sentence summaryDisruption of KEA-mediated chloroplast ion homeostasis in Chlamydomonas reinhardtii reveals conserved and lineage-specific control of plastid rRNA processing and cell cycle progression.

plant biology↗

bioRxiv2025

EEG frequency-tagging captures the neural integration of bilateral periodic thermonociceptive stimulation

Sustained periodic stimuli are known to elicit a periodic neural response (i.e. steady-state evoked potential) in the EEG frequency spectrum. These responses can easily be traced at their frequency of stimulation and corresponding harmonics using a frequency-tagging approach. To date, sustained periodic thermonociceptive stimuli have only been used on one extremity (e.g. right volar forearm) at a time. Extending this procedure to sustained stimulation applied concomitantly to distinct limbs would allow us to study the mechanisms of integration or competition between sensory signals from these different body locations. This study demonstrates that slow, sustained, sinusoidal thermonociceptive stimuli, bilaterally applied using two different stimulation frequencies (i.e. f1, f2, one on each forearm), elicit two distinct neural periodic responses at the respective frequency of stimulation and their harmonics. Additionally, we showed preliminary evidence for an interaction between the neural populations involved in the response to these stimuli, marked by neural activity at intermodulation frequencies (n* f1 {+/-} m* f2). So far, this non-linear integration of sensory information has already been observed following visual and auditory stimuli but not yet following thermonociceptive stimuli. New and noteworthyThis study demonstrates that sustained, slow, sinusoidal thermonociceptive stimulation applied simultaneously to both forearms at different frequencies elicits distinct neural responses at each stimulation frequency and its harmonics. Moreover, we provide preliminary evidence for interaction between the neural populations involved in the response to these stimuli during bilateral thermonociceptive stimulation. These findings extend frequency-tagging approaches in pain research and reveal potential non-linear sensory integration of distinct thermo-nociceptive inputs.

neuroscience↗

bioRxiv2020

SimText: A text mining framework for interactive analysis and visualization of similarities among biomedical entities

Literature exploration in PubMed on a large number of biomedical entities (e.g., genes, diseases, experiments) can be time consuming and challenging comparing many entities to one other. Here, we describe SimText, a user-friendly toolset that provides customizable and systematic workflows for the analysis of similarities among a set of entities based on words from abstracts and/or other text. SimText can be used for (i) data generation: text collection from PubMed and extraction of words with different text mining approaches, and (ii) interactive analysis of data using unsupervised learning techniques and visualization in a Shiny web application.Availability and Implementation We developed SimText as an open-source R software and integrated it into Galaxy, an online data analysis platform. A command line version of the toolset is available for download from GitHub at https://github.com/mgramm1/simtext.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioinformatics↗

bioRxiv2019

Genetic correlation between background EEG oscillations and genetic generalized epilepsy

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations. MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a GWAS on epilepsy (n=12,803 people with epilepsy and 24,218 controls) with that from a GWAS on background EEG (n=8,425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta and theta. We replicated our findings in an independent epilepsy replication dataset (n=4851 people with epilepsy and 20,428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores and Mendelian randomization analyses. ResultsOur analyses show strong genetic correlations between genetic generalized epilepsy (GGE) with background EEG oscillations, primarily with the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations. SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic work-up of epilepsy.

genetics↗

bioRxiv2019

Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,364 controls of European ancestry. We focused on three phenotypic groups; the rare but severe developmental and epileptic encephalopathies (DEE), and the commoner phenotypes of genetic generalized epilepsy (GGE) and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy, with the strongest enrichment seen in DEE and the least in NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, while no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEE and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the top associations, including CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study confirms a convergence in the genetics of common and rare epilepsies associated with ultra-rare coding variation and highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology in the largest epilepsy WES study to date.

genetics↗