Biology subjects

Perron, M.

Publications and source records attributed to Perron, M..

13 recordsLinked to original sources

bioRxiv2026

Non-Linear Dorsolateral Prefrontal Recruitment During Speech-in-Noise Perception in Aging

Age-related speech-in-noise difficulties have been associated with increased activity in prefrontal regions. Whether this upregulation reflects adaptive compensation, neural inefficiency, or changes in task engagement as listening demands increase remains unresolved. Most studies have relied on linear contrasts of task difficulty, limiting our understanding of how the role of prefrontal recruitment evolves with listening demand. The present study examined these competing accounts within a non-linear framework. Using functional near-infrared spectroscopy, we measured activity in the dorsolateral prefrontal cortex (DLPFC) while 36 young and 34 older adults performed a sentence-in-noise task across five signal-to-noise ratio conditions. We tested whether DLPFC recruitment followed a quadratic trajectory across listening demands and whether its relationship with performance changed accordingly. Dorsomedial and ventrolateral prefrontal activity was also recorded to assess regional specificity. Bilateral DLPFC responses followed an inverted U-shaped pattern, increasing from easier to intermediate conditions before declining at the most difficult levels. Greater left DLPFC activation was associated with poorer performance in older adults across the ascending and peak portions of the demand-response function. High-performing older adults showed more youth-like recruitment profiles characterized by lower overall activation. Within the older adult group, higher left DLPFC activation was associated with greater age but not with hearing or global cognition. These results clarify the neural mechanisms underlying age-related speech-in-noise difficulties, suggesting that the shape of DLPFC recruitment reflects a demand-sensitive trajectory broadly preserved across age groups, while the level of activation in older adults may reflect neural processing efficiency, with greater upregulation associated with poorer performance.

neuroscience↗

bioRxiv2025

Variation in bud phenology, frost tolerance and non-structural carbohydrates among white spruce seed sources on climate-contrasted test sites: implications for assisted migration

To assess the potential impacts of climate change on white spruce local adaptation, six seed sources were evaluated seven years after plantation on two test sites with contrasting growing conditions and latitude in Quebec. Bud set, frost tolerance and analysis of non-structural carbohydrates (NSC) content showed important effects of test sites, seed sources, and their interactions on bud set phenology and growth. The average bud set initiation occurred one week later in the southern site compared to the northern site, whereas the late stage of bud set was similar between sites. Significant differences were observed between seed sources for some phenological stages. Frost tolerance was significantly lower in the southern site and below -12 {degrees}C for all seed sources sampled at the beginning of October. The trend in fructose and glucose content was opposite between sites in September. It decreased from September to October in the southern site and increased in the northern site, while sucrose content showed an opposite pattern, with the southwestern seed source harboring the lowest sucrose content. NSC content was also correlated to frost tolerance. Our study highlighted the crucial role of NSC in cold hardiness to early fall frosts and local adaptation. Implications for assisted migration are discussed.

plant biology↗

bioRxiv2025

Optimizing marker density for maximizing the accuracy of genomic prediction and heritability estimates in three major North American and European spruce species

Genomic prediction, also called genomic selection (GS), is being increasingly used in tree breeding with aim to accelerate genetic gains by shortening the long breeding cycles. However, high genotyping costs remain a challenge. This study aimed to determine the optimal marker density in genome coverage, to maximize GS accuracy and precision of heritability estimates for growth and wood quality traits. Thousands of SNPs representative of the exome of three major spruce species were used: 18,275 SNPs for black spruce (representing 10,894 distinct gene loci), 11,328 SNPs for white spruce (8647 gene loci), and 116,765 SNPs for Norway spruce (20,695 gene loci). For each species, a similar experimental design was used with related full-sib families replicated on two sites, and GBLUP prediction models were developed. The effect of varying the number of SNPs was examined by re-sampling subsets from 500 to 100,000 SNPs. Results indicated that plateaus in heritability estimates were reached as the marker density increased, stabilizing between 4000 to 8000 SNPs for a spruce genome size of around 2000 centimogans, a trend consistent across all traits and species. Predictive ability and prediction accuracy both increased with the number of SNPs up to a similar level, beyond which further improvements were marginal. Such optimal marker density should be financially attainable for most spruce breeding programs, striking a balance between the need for maximizing accuracy and that for minimizing genotyping costs. These findings should support the further deployment of GS in conifer breeding programs, with high selection precision and by reducing the financial burden of very high-density SNP coverage, even for conifers characterized by large giga-genomes.

genomics↗

bioRxiv2025

Development and validation of an exome-wide SNP genotyping array for genomic prediction, GWAS and assessment of introgressive hybridization between black and red spruces, and transferability to white and Norway spruces

Introgressive hybridization plays a major role in shaping the evolutionary dynamics and adaptive potential of forest trees. In this study, we developed and validated an exome-wide bispecific SNP genotyping array (Pmr25k) for the closely related species black spruce (Picea mariana) and red spruce (Picea rubens), two ecologically and economically important North American conifers that form a widespread hybrid zone in eastern Canada. Exome capture and sequencing of pooled red spruce samples yielded over 25,000 high-quality SNPs, which were used in conjunction with a previously developed black spruce gene SNP resource of over 97,000 high-quality SNPs, to construct the bispecific genotyping array. The final array comprised 21,573 successfully manufactured SNPs, representing 14,200 distinct gene loci, of which 85% were segregating when both species were considered together. More than 4000 segregating SNPs could also be successfully used and genotyped in each of white spruce (Picea glauca) and Norway spruce (Picea abies), highlighting the conserved nature of DNA attachment sites and presence of homologous SNPs for many gene loci. The Pmr25k array thus provides an efficient and reliable high-throughput genotyping tool to investigate introgression, genetic adaptation at the gene level, and to assist genomic-based prediction for breeding and conservation efforts in boreal spruces.

genomics↗

bioRxiv2024

Spruce hybrids show superior cumulative growth and intermediate response to climate anomalies, as compared to their ecologically divergent parental species

Climate change brings new constraints to which trees will have to adapt, including more frequent weather extremes. Black spruce and red spruce are phylogenetically close but adapted to different ecological conditions, and they form a natural hybrid zone where their distributions come into contact. Thus, they represent an interesting model to study the effect of introgressive hybridization in the context of climate change, given that interspecific gene flow could affect their capacity to adapt where their natural distributions overlap. Using a common-garden field test gathering 20-year-old progeny trees resulting from rigorous controlled crosses including previously verified genetic identity of the parents, growth patterns and wood density differences could be observed between species and between them and their F1 hybrids. A dendroecological analytical approach relying on wood cores was used and revealed similar wood responses to climatic variations between species, both through lifetime climate sensitivity and through episodic stress response indexes. They were however differentially expressed in early- and latewood between black spruce and red spruce, differences likely driven by diverging cambial phenology adaptations to different growing season lengths. F1 hybrids exhibited hybrid vigor for cumulative growth under the test site conditions, but showed intermediate values for traits related to climate response. These results offer new perspectives for understanding the dynamics of adaptation in hybrid zones in the context of climate change, as well as for guiding conservation and genetic improvement efforts. HighlightsO_LIF1 cumulative growth is higher than their ecologically contrasted parents. C_LIO_LIHybrids had intermediate climate responses C_LIO_LIParental species responded similarly to climate anomalies, but in various intra-ring part. C_LIO_LICambial phenology likely drives divergences in wood reaction to climate anomalies C_LI

plant biology↗

bioRxiv2024

Discovery and Synthesis of GS-7682, a Novel Prodrug of a 4'-CN-4-Aza-7,9-Dideazaadenosine C-Nucleoside with Broad-Spectrum Potency Against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys.

Acute respiratory viral infections (ARVI), such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1) a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV EC50 = 3-46 nM, human metapneumovirus (hMPV) EC50 = 210 {+/-} 50 nM, human rhinovirus (RV) EC50 = 54-61 nM, and enterovirus (EV) EC50 = 83-90 nM. Prodrug optimization for cellular potency and lung cell metabolism identified the 5-methyl((S)-hydroxy(phenoxy)phosphoryl)-L-alaninate in combination with 2,3-diisobutyrate promoieties as optimal for high intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together these finding support additional evaluation of 1 and its analogs as a potential therapeutic for pneumo- and picornaviruses.

biochemistry↗

bioRxiv2024

Assessing Cognitive Functions Remotely Using a Music-Game-Like Program

There is a growing need to develop ways of assessing cognitive functions remotely and providing interventions using a web-based approach. The Ipsilon Test is a music-based cognitive assessment and training tablet application. On each trial, it presents simplified musical notation with colours, spatial cues, and gestural references so that users can translate spatial information into motor actions by tapping on the screen. In this study, we examined the correlation between the performance of a group of healthy older adults on the Ipsilon test and standard measures of cognitive function--a total of 30 participants aged 58 and over were recruited for the study. Before and after one week of training using the web-based program Ipsilon, all participants completed an online version of the Montreal Cognitive Assessment (MoCA) and the visual Stroop task. Of the participants recruited, 22 participants completed the Ipsilon training and cognitive testing. In our sample, performance on the Ipsilon test was generally high, with all participants scoring above the chance level. Importantly, we found a correlation between Ipsilon test performance and pre-Ipsilon MoCA scores. In addition, participants who scored higher on the Ipsilon test also showed improvement in the visual Stroop task after Ipsilon training, particularly in the ability to inhibit irrelevant information. These results suggest the Ipsilon test is a practical web-based cognitive assessment and training tool. Future research will explore its relationship with other cognitive tests and its diagnostic power for differentiating individuals with normal cognition from those with cognitive disorders.

neuroscience↗

bioRxiv2023

Regeneration from three cellular sources and ectopic mini-retina formation upon neurotoxic retinal degeneration in Xenopus

Regenerative abilities are not evenly distributed across the animal kingdom. Interestingly, the underlying modalities are also highly variable, even among closely related species. In fish or amphibians, retinal repair can involve the mobilization of different cellular sources, including stem cells of the ciliary marginal zone (CMZ), retinal pigmented epithelial (RPE) cells, or Muller glia. The mechanisms that trigger the recruitment of one cell type over another remain elusive. To investigate whether the magnitude of retinal damage might influence the regeneration modality of the Xenopus retina, we developed a model based on cobalt chloride (CoCl2) intraocular injection, allowing for a dose-dependent control of cell death extent. Analyses in Xenopus laevis revealed that limited CoCl2-mediated neurotoxicity only triggers cone cell loss and results in a few Muller glia cells reentering the cell cycle, without affecting CMZ cell activity or recruiting RPE cells. Conversely, we found that severe CoCl2-induced retinal degeneration not only potentializes the proliferative response of Muller cells, but also enhances CMZ cell proliferation and, unexpectedly triggers an RPE reprogramming event. Although Muller glia could not regenerate cones under these conditions, both CMZ and RPE-derived proliferative cells could. Strikingly, RPE reprogrammed cells self-organized into an ectopic layered mini retina-like structure laid on top of the original retina. It is thus likely that the injury paradigm determines the awakening of different stem-like cell populations exhibiting distinct neurogenic capacities. Besides, we surprisingly found that Xenopus tropicalis also has the ability to recruit Muller cells and reprogram its RPE following CoCl2-induced damage, whereas only CMZ cell proliferation was reported in previously examined degenerative models. Altogether, these findings highlight the critical role of the injury paradigm and reveal that three cellular sources can be reactivated in the very same degenerative model.

developmental biology↗

bioRxiv2022

Awakening adult neural stem cells: NOX signalling as a positive regulator of quiescence to proliferation transition in the Xenopus retina

Reactive oxygen species (ROS) are both harmful molecules sustaining the pathogenesis of several diseases and essential modulators of cell behaviours. In particular, a growing wealth of data suggest that ROS-dependent signalling pathways might be critical in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ROS production and scavenging, and how ROS in turn contribute to stemness remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared to progenitors and retinal neurons and express a set of specific antioxidant genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase (NOX)-dependent ROS production increases the proportion of quiescent RSCs. This is surprisingly accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NOX signalling to limit quiescence and fine-tune their proliferation rate.

developmental biology↗

bioRxiv2022

Late-onset glaucoma in Yap conditional knockout mouse

Glaucoma is an optic neuropathy often referred to as "the silent thief of sight", due to its late diagnosis, which is generally made when degeneration of the optic nerve and retinal ganglion cells is already well under way. It is thus of utmost importance to have a better understanding of the disease, and to investigate more deeply the early causes of glaucoma. The transcriptional coactivator YAP recently emerged as an important regulator of eye homeostasis and is drawing attention in the glaucoma research field. Here we show that Yap conditional knockout mice (Yap cKO), in which the deletion of Yap is induced in both Muller glia (i.e. the only retinal YAP-expressing cells) and the non-pigmented epithelial cells of the ciliary body, exhibit breakdown of the aqueous-blood barrier accompanied by progressive collapse of the ciliary body as we observed in human uveitic patients. In addition, aged Yap cKO mice harbor glaucoma features, including alteration of glutamate recycling, deregulation of key homeostatic Muller-derived proteins, retinal vascular defects, optic nerve degeneration, and retinal ganglion cell death. Together, our findings reveal the essential role of YAP in preserving the ciliary body and the retinal ganglion cells, thereby preventing the onset of glaucoma features.

neuroscience↗

bioRxiv2021

A non-transcriptional function of Yap orchestrates the DNA replication program

In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signaling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and that Yap depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. Furthermore, we identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that both Yap and Rif1 depletion trigger an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as breaks to control the DNA replication program in early embryos and post-embryonic stem cells. HighlightsO_LIYap is recruited to chromatin during DNA replication dependent on pre-replicative complex assembly. C_LIO_LIYap controls DNA replication dynamics by limiting origin firing. C_LIO_LIThe replication timing regulatory factor 1, Rif1, is a novel Yap binding-partner. C_LIO_LIBoth Yap and Rif1 regulate the length of the first embryonic cell cycles. C_LIO_LILike Yap, Rif1 controls retinal stem cell DNA replication timing. C_LI

developmental biology↗

bioRxiv2020

Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Muller glia. We first discovered an unexpected temporal dynamic of gene compensation. At post-natal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterized by EGFR signalling potentiation and delayed cell cycle exit of retinal progenitors. In contrast, Yap+/- adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Muller glia dysfunction, late-onset cone degeneration and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Muller cell specific conditional Yap knockout mice. Together, this study highlights a novel YAP function in Muller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/953943v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@166de41org.highwire.dtl.DTLVardef@898b74org.highwire.dtl.DTLVardef@22ad92org.highwire.dtl.DTLVardef@b189dc_HPS_FORMAT_FIGEXP M_FIG C_FIG Main Points O_LIThis study finds unsuspected dynamics of YAP compensatory mechanisms in the retina of Yap+/- mice C_LIO_LIYap haploinsufficiency results in Muller glia dysfunction in aged mice, leading to late-onset cone dystrophy C_LI

neuroscience↗

bioRxiv2018

Linking YAP to Müller glia quiescence exit in the degenerative retina

Contrasting with fish or amphibian, retinal regeneration from Muller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Muller cells following retinal injury. We report that conditional Yap deletion in Muller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Muller glia cell cycle re-entry, we further show that in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Muller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Muller cell response to injury and highlight a novel YAP-EGFR axis by which Muller cells exit their quiescence state, a critical step towards regeneration.

developmental biology↗