Biology subjects

Beckers, L.

Publications and source records attributed to Beckers, L..

4 recordsLinked to original sources

bioRxiv2023

Convergent neural signatures of speech prediction error across space, time and frequency

We used MEG and fMRI to determine how predictions are combined with speech input in superior temporal cortex. We compared neural responses to bisyllabic spoken words in which the first syllable strongly or weakly predicts the form of the second syllable (e.g. "bingo" versus "tango"). We further compared neural responses to the same second syllables when heard in an unfamiliar pseudoword and therefore in a situation in which predictions mismatch with sensory input (e.g. "snigo" and "meago"). Across multiple imaging modalities and analysis approaches (including information-based pattern analysis methods), we show that neural representations of second syllables are suppressed by strong predictions when predictions match sensory input. However, neural representations of the same second syllables show the opposite effect (i.e. enhanced representations following strongly than weakly-predicting syllables) when predictions mismatch with sensory input. Computational simulations show that this interaction between prediction strength and (mis)match is consistent with prediction error but not alternative (sharpened signal) computations. Neural signatures of prediction error are observed early (beginning 200 ms after the onset of the second syllable), localise to early auditory regions (in fMRI, bilateral Heschls gyrus and STG) and are expressed as changes in low-frequency (theta and alpha) power. Our study therefore provides convergent neural evidence that speech perception is supported by the computation of prediction errors in auditory brain regions. These prediction error computations play a central role in the identification of familiar spoken words and perception of unfamiliar pseudowords.

neuroscience↗

bioRxiv2022

A rich get richer effect governs intracellular condensate size distributions

Phase separation of biomolecules into condensates has emerged as a ubiquitous mechanism for intracellular organization and impacts many intracellular processes, including reaction pathways through clustering of enzymes and their intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here, we utilize a combination of synthetic and native condensates to probe the underlying physical mechanisms determining condensate size. We find that both native nuclear speckles and FUS condensates formed with the synthetic Corelet system obey an exponential size distribution, which can be recapitulated in Monte Carlo simulations of fast nucleation followed by coalescence. By contrast, pathological aggregation of cytoplasmic Huntingtin polyQ protein exhibits a power-law size distribution, with an exponent of -1.41 {+/-} 0.02. These distinct behaviors reflect the relative importance of nucleation and coalescence kinetics: introducing continuous condensate nucleation into the Monte Carlo coarsening simulations gives rise to polyQ-like power-law behavior. We demonstrate that the emergence of power-law distributions under continuous nucleation reflects a "rich get richer" effect, whose extent may play a general role in the determination of condensate size distributions.

biophysics↗

bioRxiv2022

Viscoelastic RNA entanglement and advective flow underlie nucleolar form and function

The nucleolus facilitates transcription, processing, and assembly of ribosomal RNA (rRNA), the most abundant RNA in cells. Nucleolar function is facilitated by its multiphase liquid properties, but nucleolar fluidity and its connection to ribosome biogenesis remain unclear. Here, we used quantitative imaging, mathematical modeling, and pulse-chase nucleotide labelling to map nucleolar rRNA dynamics. Inconsistent with a purely diffusive process, rRNA steadily expands away from the transcriptional sites, moving in a slow (~1[A]/s), radially-directed fashion. This motion reflects the viscoelastic properties of a highly concentrated gel of entangled rRNA, whose constant polymerization drives steady outward flow. We propose a new viscoelastic rRNA release model, where nucleolar rRNA cleavage and processing reduce entanglement, fluidizing the nucleolar periphery to facilitate release of mature pre-ribosomal particles.

biophysics↗

bioRxiv2019

A Novel Tmem119-tdTomato Reporter Mouse Model for Studying Microglia in the Central Nervous System

Microglia are resident immune cells of the central nervous system (CNS). The exact role of microglia in the physiopathology of CNS disorders is not clear due to lack of tools to discriminate between CNS resident and infiltrated innate immune cells. Here, we present a novel reporter mouse model targeting a microglia-specific marker (TMEM119) for studying the function of microglia in health and disease. By placing a reporter cassette (GSG-3xFlag-P2A-tdTomato) between the coding sequence of exon 2 and 3UTR of the Tmem119 gene using CRISPR/Cas9 technology, we generated a Tmem119-tdTomato knock-in mouse strain. Gene expression assay showed no difference of endogenous Tmem119 mRNA level in the CNS of Tmem119tdTomato/+ relative to control Wild-type mice. The cells expressing tdTomato-were recognized by immunofluorescence staining using commercially available anti-TMEM119 antibodies. Using immunofluorescence and flow cytometry techniques, tdTomato+ cells were detected throughout the CNS, but not in peripheral tissues of adult Tmem119tdTomato/+ mice. In addition, aging does not seem to influence TMEM119 expression as tdTomato+ cells were detectable in the CNS of older mice (300 and 540 days old). Further immunofluorescence characterization shows that the tdTomato+ cells were highly colocalized with Iba1+ cells (microglia and macrophages) in the brain, but not with NeuN- (neurons), GFAP- (astrocytes) or Olig2- (oligodendrocytes) labeled cells. Moreover, flow cytometry analysis of brain tissues of adult mice demonstrates that the majority of microglial CD45lowCD11b+ cells (96.6%) are tdTomato positive. Functionally, using a laser-induced injury model, we measured time-lapse activation of tdTomato-labeled microglia by transcranial two-photon microscopy in live Tmem119tdTomato/+ mice. Taken together, the Tmem119-tdTomato reporter mouse model will serve as a valuable tool to specifically study the role of microglia in health and disease.

immunology↗