Biology subjects

Maillard, L.

Publications and source records attributed to Maillard, L..

8 recordsLinked to original sources

bioRxiv2026

In vivo isogenic modelling unveils a TP53-mediated relapse phenotype in T-cell acute lymphoblastic leukemia

Many patients with T-cell acute lymphoblastic leukemia (T-ALL) relapse into a treatment-resistant disease. The mechanisms driving relapse remain largely elusive, in part due to the lack of faithful experimental models. Here, we leveraged patient-derived xenograft (PDX) pairs generated from diagnosis and relapse T-ALLs to functionally address the cellular mechanisms driving TP53-altered relapse. Beyond inter-T-ALL variability, comparative analyses revealed a unique, cell-intrinsic relapse phenotype that includes greater leukemia-initiating capacity and that can be conferred to diagnosis cells by TP53 silencing. Transcriptomic profiling linked the relapse phenotype to deregulated OXPHOS metabolism and MYC signaling. Integration of single-cell profilings uncovered TP53-wildtype cell populations at diagnosis expressing a relapse profile, possibly reflecting a pre-existing modulation of TP53 signaling. These cells sequentially evolved towards biallelic TP53 inactivation at relapse. Collectively, our findings support a model in which T-ALL relapses emerge from a selected pre-existing transcriptional state characterized by deregulated metabolism that favors subsequent TP53 inactivation.

cancer biology↗

bioRxiv2025

Choosing the best or avoiding the worst: complementary and opponent value signals in the human brain

Whether the brain encodes the subjective value of pleasant and unpleasant situations via a single integrated circuit or through distinct pathways remains unresolved. It is also unclear how neural value signals guide choices when the context involves choosing the most favorable option or avoiding the most unfavorable one. To address these questions, we recorded intracerebral activity from 27 participants as they first rated pleasant and unpleasant scenarios and then made binary choices across all combinations of item domain (pleasant/unpleasant) and choice frame (choose best/worst). Ventromedial prefrontal cortex (vmPFC) broadband gamma activity (BGA, 50-150 Hz) tracked the value of pleasant items during rating and pre-choice, correlating positively with the most pleasant item irrespective of choice frame. Similarly, anterior insula (aIns) BGA tracked the value of unpleasant items during rating and pre-choice, correlating negatively with the most unpleasant item irrespective of choice frame. The difference in relative value correlations between the vmPFC and aIns was larger for choices involving a conflict between item domain and choice frame, consistent with slower response times and choices less aligned with value differences in these trials. These findings reveal dissociable yet complementary neural systems for pleasant and unpleasant valuation and highlight how such signals may guide flexible decision-making across contexts.

neuroscience↗

bioRxiv2024

Dissecting the dynamics of coordinated active transcriptional repression in a multicellular organism

Refining transcriptional levels via active repression in an euchromatic context represents a critical regulatory process. While the molecular players of active repression are well described, their dynamics remain obscure. Here, we used snail expression dynamics as a paradigm to uncover how repression, mediated by the Snail (Sna) repressor, can be imposed within a developing tissue. Combining live imaging and mathematical modeling, we show that Sna-mediated repression is cooperative and that cooperativity is primarily mediated by the distal enhancer. Repression shifts transcription bursting dynamics from a two-state ON/OFF regime to a three-state repressed regime with two temporally distinct OFF states. Mutating Sna binding sites suggests that repression introduces the long-lasting inactive state, which is stabilized by cooperativity. Our approach offers quantitative insights into the dynamics of repression and how transcription factor cooperativity coordinates cell fate decisions within a tissue.

molecular biology↗

bioRxiv2022

Mechanical properties of breast, kidney, and thyroid tumours measured by AFM: relationship with tissue structure

The mechanical properties of the extracellular matrix are essential for regulating cancer cell behaviour, but how they change depending on tumour type remains unclear. The aim of the current study was to determine how the mechanical properties of tumours that frequently metastasize to bones were affected depending on histological type. Human breast, kidney, and thyroid specimens containing tumour and normal tissue were collected during surgery. The elastic modulus and elastic fraction of each sample were characterised using atomic force microscopy and compared with histopathological markers. We observed that tumour mechanical properties were differentially affected depending on organ and histological type. Indeed, clear cell renal carcinoma and poorly differentiated thyroid carcinoma displayed a decrease in the elastic modulus compared to their normal counterpart, while breast tumours, papillary renal carcinoma and fibrotic thyroid tumours displayed an increase in the elastic modulus. Elastic fraction decreased only for thyroid tumour tissue, indicating an increase in the viscosity. These findings suggest a unique mechanical profile associated with each subtype of cancer. Therefore, viscosity could be a discriminator between tumour and normal thyroid tissue, while elasticity could be a discriminator between the subtypes of breast, kidney and thyroid cancers. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/495321v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1372cddorg.highwire.dtl.DTLVardef@1628197org.highwire.dtl.DTLVardef@2a0103org.highwire.dtl.DTLVardef@1a89b3a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Low and high frequency intracranial neural signals match in the human associative cortex

In vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (<30 Hz, LF) and broadband activity in the higher end of the frequency spectrum (>30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure selective responses to complex ecologically salient visual stimuli - human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.

neuroscience↗

bioRxiv2021

Intracerebral mechanisms explaining the impact of incidental feedback on mood state and risky choice

Identifying factors whose fluctuations are associated with choice inconsistency is a major issue for rational decision theory. Here, we investigated the neuro-computational mechanisms through which mood fluctuations may bias human choice behavior. Intracerebral EEG data were collected in a large group of participants (n = 30), while they were performing interleaved quiz and choice tasks. Neural baseline activity preceding choice onset was confronted first to mood level, estimated by a computational model integrating the feedbacks received in the quiz task, and then to the weighting of option attributes, in a computational model predicting risk attitude in the choice task. Results showed that 1) elevated broadband gamma activity (BGA) in the ventromedial prefrontal cortex (vmPFC) and dorsal anterior insula (daIns) was respectively signaling periods of high and low mood, 2) increased vmPFC and daIns BGA respectively promoted and tempered risk taking by overweighting gain versus loss prospects. Thus, incidental feedbacks induce brain states that correspond to different moods and bias the comparison of safe and risky options. More generally, these findings might explain why people experiencing positive (or negative) outcome in some part of their life tend to expect success (or failure) in any other.

neuroscience↗

bioRxiv2020

Dissociated face- and word-selective intracerebral responses in the human ventral occipito-temporal cortex

The extent to which faces and written words share neural circuitry in the human brain is actively debated. Here we compared face-selective and word-selective responses in a large group of patients (N = 37) implanted with intracerebral depth electrodes in the ventral occipito-temporal cortex (VOTC). Both face-selective (i.e., significantly different responses to faces vs. nonface visual objects) and word-selective (i.e., significantly different responses to words vs. pseudofonts) neural activity is isolated through frequency-tagging. Critically, this sensitive approach allows to objectively quantify category-selective neural responses and disentangle them from general visual responses. About 70% of significant contacts show either only face-selectivity or only word-selectivity, with the expected right and left hemispheric dominance, respectively. Spatial dissociations are also found within core regions of face and word processing, with a medio-lateral dissociation in the fusiform gyrus (FG) and surrounding sulci, while a postero-anterior dissociation is found in the inferior occipital gyrus (IOG). Only 30% of the significant contacts show both face- and word-selective responses. Critically, in these contacts, across the VOTC or in the FG and surrounding sulci, between-category selective-amplitudes (faces vs. words) showed no-to-weak correlations, despite strong correlations in both the within-category selective amplitudes (face-face, word-word) and the general visual responses to words and faces. Overall, we conclude that category-selectivity for faces and written words is largely dissociated in the human VOTC. Significance StatementIn modern human societies, faces and written words have become arguably the most significant stimuli of the visual environment. Despite extensive research in neuropsychology, electroencephalography and neuroimaging over the past three decades, whether these two types of visual signals are recognized by similar or dissociated processes and neural networks remains unclear. Here we provide an original contribution to this outstanding scientific issue by directly comparing frequency-tagged face- and word-selective neural responses in a large group of epileptic patients implanted with intracerebral electrodes covering the ventral occipito-temporal cortex. While general visual responses to words and faces show significant overlap, the respective category-selective responses are neatly dissociated in spatial location and magnitude, pointing to largely dissociated processes and neural networks.

neuroscience↗

bioRxiv2017

A Face Identity Hallucination (Palinopsia) Generated By Intracerebral Stimulation Of The Face-Selective Right Lateral Fusiform Cortex

We report the case of a patient (MB, young female human subject) who systematically experiences confusion between perceived facial identities when electrically stimulated inside the lateral section of the right fusiform gyrus. In the presence of a face stimulus (an experimenter or a photograph), intracerebral electrical stimulation in this region generates a perceptual hallucination of an individual facial part integrated within the whole perceived face, i.e. facial palinopsia. In the presence of a distracting stimulus (visual scene or object picture), the patient also experiences an individual face percept superimposed on the non-face stimulus. The stimulation site evoking this category-selective transient palinopsia is localized in a region showing highly selective responses to faces both with functional magnetic resonance imaging (\"Fusiform Face Area\", \"FFA\") and intracerebral electrophysiological recordings during fast periodic visual stimulation (FPVS). Importantly, the largest electrophysiological response to fast periodic changes of facial identity is also found at this location. Altogether, these observations suggest that a local face-selective region of the right lateral fusiform gyrus suffices to generate a vivid percept of an individual face, supporting the active role of this region in individual face representation.

neuroscience↗