Biology subjects

Berry, I.

Publications and source records attributed to Berry, I..

6 recordsLinked to original sources

bioRxiv2026

Metallothionein loss in cancer cells contributes to increased mutations through defective DNA repair and metabolic imbalance

Understanding which genes are involved in mutagenesis is essential for developing cancer prevention and treatment strategies; establishing protectors of the genome has revolutionized cancer biology. Here, we describe metallothionein (MT) proteins as previously uncharacterized protectors against mutagenesis. MT is a heavy metal binding protein essential for zinc homeostasis and protection against heavy metal cytotoxicity. Because zinc binds approximately 10-15% of the proteome and is critical for processes such as DNA repair and mitochondrial health, MT loss is expected to disrupt these processes. We hypothesized that MT loss induces genomic instability by impairing DNA repair and mitochondrial function. In this study, the consequences of MT deficiency in high-grade serous ovarian cancer (HGSC) were investigated by knockdown of the most highly expressed MT, MT2A. Loss of MT2A resulted in the impaired DNA repair pathway base excision repair (BER), leading to increased mutagenesis. MT2A deficiency produced mitochondrial dysfunction, characterized by a decrease in mitochondrial membrane potential, glycolysis, oxidative phosphorylation, amino acids, and an imbalance of nucleobases. Together, these defects reflect cellular states associated with increased cancer aggressiveness. These findings identify MT as a fundamental hub maintaining genomic and metabolic integrity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/736843v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1af4adeorg.highwire.dtl.DTLVardef@15c588forg.highwire.dtl.DTLVardef@1ba5181org.highwire.dtl.DTLVardef@13d150b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Cerebral Bases and Neural Dynamics of Audiovisual Temporal Binding Window: a TMS study

The temporal binding window (TBW) refers to the time interval within which two stimuli, typically visual and auditory, are perceived as synchronous. Neural bases underlying this process consistently implicate a large-scale network with superior temporal sulcus (STS) as a central hub, alongside contributions from primary auditory and visual cortices and higher-order areas including prefrontal and posterior parietal cortex. This study aimed to provide causal evidence for the involvement of superior temporal gyrus (STG) and intraparietal sulcus (IPS) in the simultaneity judgment (SJ) task using MRI-guided transcranial magnetic stimulation (TMS). In particular, we aimed to clarify temporal dynamics of these regions in audiovisual synchrony perception. Forty adults performed an SJ task in which they had to determine whether stimuli were synchronous or asynchronous. Single-pulse TMS was applied over bilateral IPS, STG, or the vertex at different delays following stimulus offset. Early stimulation of left IPS and right STG increased the proportion of "synchronous" responses. In contrast, later stimulation of bilateral STG was associated with reduced synchrony perception. These findings provide causal evidence for a dynamic interplay between parietal and temporal regions in audiovisual temporal integration. Early IPS and STG involvement facilitates temporal integration, while later STG activity promotes perceptual segregation.

neuroscience↗

bioRxiv2025

Modality-Agnostic Decoding of Vision and Language from fMRI

Humans perform tasks involving the manipulation of inputs regardless of how these signals are perceived by the brain, thanks to representations that are invariant to the stimulus modality. In this paper, we present modality-agnostic decoders that leverage such modality-invariant representations to predict which stimulus a subject is seeing, irrespective of the modality in which the stimulus is presented. Training these modality-agnostic decoders is made possible thanks to our new large-scale fMRI dataset SemReps-8K, released publicly along with this paper. It comprises 6 subjects watching both images and short text descriptions of such images, as well as conditions during which the subjects were imagining visual scenes. We find that modality-agnostic decoders can perform as well as modality-specific decoders, and even outperform them when decoding captions and mental imagery. Further, a searchlight analysis revealed that large areas of the brain contain modality-invariant representations. Such areas are also particularly suitable for decoding visual scenes from the mental imagery condition.

neuroscience↗

bioRxiv2025

Motion processing in visual cortex of maculopathy patients

Previous studies on animal models suggested that visual areas involved in motion processing could undergo important cortical reorganizations following retinal damages. This could have major implications for patients suffering from macular degeneration (MD), one leading cause of vision loss. Here, we performed fMRI recordings in a group of maculopathy patients (including individuals suffering from age-related macular degeneration or from Stargardts Disease) and a control group to characterize the motion processing cortical network in MD patients and determine whether this network is modified following the onset of the scotoma. We used an experimental protocol based on random-dot kinematograms (RDKs) classically employed to characterize motion-selective areas in the brain. To ensure that the visual information processed by the two groups was equivalent, the visual field in each control participant was masked using an artificial scotoma directly derived from clinical measurements in their paired patient. We found that in MD patients, translational motion elicited significant and robust activations in a restricted cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas (V1, V2 and V3) connected to peripheral vision. Importantly, the same patterns of responses were also observed in control participants. Moreover, the extent and strength of activation within these motion-selective areas did not differ significantly between the two groups. Altogether, these results suggest that in humans, the motion-selective network does not undergo significant large-scale cortical reorganizations following the onset of MD. Significance statementMotion processing in the visual cortex of patients with macular degeneration has never been characterized. Here, we performed fMRI recordings in 7 maculopathy patients and found robust motion-selective activations in a cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas connected to peripheral vision. These activations closely align with those reported in participants with normal vision in the literature and do not significantly differ from those measured in a group of age and gender-matched control participants who viewed the motion stimuli with a matched artificial scotoma. Altogether, our results suggest that the motion-selective network does not undergo significant large-scale reorganizations in maculopathy patients following the onset of the scotoma.

neuroscience↗

bioRxiv2021

Auditory cortex activation is modulated nonlinearly by stimulation duration: A functional near-infrared spectroscopy (fNIRS) study

Functional near-infrared spectroscopy (NIRS) is an increasingly popular method in hearing research. However, few studies have considered efficient stimulation parameters for fNIRS auditory experimental design. The objectives of our study are (1) to characterize the auditory hemodynamic responses to trains of white noise with increasing stimulation durations (8s, 10s, 15s, 20s) in terms of amplitude and response linearity; (2) to identify the most-efficient stimulation duration using fNIRS; and (3) to generalize results to more ecological environmental stimuli. We found that cortical activity is augmented following the increments in stimulation durations and reaches a plateau after about 15s of stimulation. The linearity analysis showed that this augmentation due to stimulation duration is not linear in the auditory cortex, the non-linearity being more pronounced for longer durations (15s and 20s). The 15s block duration that we propose as optimal precludes signal saturation, is associated with a high response amplitude and a relatively short total experimental duration. Moreover, the 15s duration remains optimal independently of the nature of presented sounds. The sum of these findings suggests that 15s stimulation duration used in the appropriate experimental setup allows researchers to acquire optimal fNIRS signal quality.

neuroscience↗

bioRxiv2021

Interpreting TMEM67 missense variants of uncertain significance (VUS) in an animal model

PurposeBetter methods are required to interpret the pathogenicity of disease-associated variants of uncertain significance (VUS), which cannot be actioned clinically. In this study, we explore the use of a tractable animal model (Caenorhabditis elegans) for in vivo interpretation of missense VUS alleles of TMEM67, a cilia gene associated with ciliopathies. MethodsCRISPR/Cas9 gene editing was used to generate homozygous knock-in C. elegans worm strains carrying TMEM67 patient variants engineered into the orthologous gene (mks-3). Quantitative phenotypic assays of sensory cilia structure and function measured if the variants affect mks-3 gene function. Results from worms were validated by a genetic complementation assay in a human TMEM67 knock-out hTERT-RPE1 cell line that tests a TMEM67 signaling function. ResultsAssays in C. elegans accurately distinguished between known benign (Asp359Glu, Thr360Ala) and known pathogenic (Glu361Ter, Gln376Pro) variants. Analysis of eight missense VUS generated evidence that three are benign (Cys173Arg, Thr176Ile, Gly979Arg) and five are pathogenic (Cys170Tyr, His782Arg, Gly786Glu, His790Arg, Ser961Tyr). ConclusionEfficient genome editing and quantitative functional assays in C. elegans make it a tractable in vivo animal model that allows rapid, cost-effective interpretation of ciliopathy-associated missense VUS alleles.

genetics↗