Biology subjects

Duchesne, E.

Publications and source records attributed to Duchesne, E..

6 recordsLinked to original sources

bioRxiv2026

Three-Year Longitudinal Analysis of Splicing Changes in Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion in the 3' untranslated region of the DMPK gene that results in the expression of expanded CUG RNA which trap splicing factors resulting in widespread alternative splicing dysregulation. A panel of these splicing events, or splicing index (SI), is currently used to measure splicing dysregulation in DM1 patients. Despite significant interest in splicing, little is known about its progression over time in DM1. The objective of this study was to evaluate the changes in SI over 3 years in a well-phenotyped cohort of DM1 participants and identify factors contributing to these changes. RNA was extracted from vastus lateralis (VL) biopsies of 20 DM1 participants taken 3 years apart and the SI score was measured using targeted RNA sequencing. Baseline SI scores correlated with percent predicted muscle strength of the ankle dorsiflexors, knee extensors and hand grip. On average, SI scores worsened over 3 years, but the progression varied markedly among participants. Adult/juvenile phenotypes and lower baseline SI scores were among the factors associated with higher progression of SI scores over time. These findings emphasize the importance of integrating clinical phenotype and baseline molecular severity when interpreting longitudinal SI change, particularly in the context of clinical trials.

bioinformatics↗

bioRxiv2025

Aligning gene trees with family trees

Relatedness between individuals can be measured at the genealogical level (by describing shared ancestors in a pedigree) or at a genetic level (by describing shared haplotypes across the genome). The shared haplotype structure can be conveniently summarized as a sequence of trees along the genome, where each tree describes the last shared genetic ancestors between individuals at a locus. While many tools exist to infer tree sequences from genetic data, and many large pedigree datasets are available, few tools exist to identify the relationship between the two - finding which genetic ancestor corresponds to which pedigree ancestor, and conversely. In this paper, we propose an algorithm to solve this problem by providing, for each genetic tree, the list of all consistent ancestry paths within a genealogical tree. We also provide variants of the algorithm with moderate robustness to both tree sequence and pedigree errors. We demonstrate the scalability of our approach on the BALSAC genealogical dataset, which includes millions of individuals in Quebec, Canada. We find that 20 carriers usually provide enough information to reliably identify a common ancestor 15 generations ago or find the parent of origin of alleles among probands, but the number of possible ancestry paths within the pedigree can remain large. We apply the method to reconstruct the inheritance of a causal allele for type 1 myotonic dystrophy.

bioinformatics↗

bioRxiv2025

Experimental and field evidence indicate that islet-nesting tundra birds experience reduced nest predation and benefit indirectly from high snow goose densities

Landscape features can shape the occurrence and strength of predator-prey interactions by influencing predation risk and prey distribution. In the High Arctic, some bird species select nesting sites with physical features that limit the access by their main terrestrial predator, the arctic fox, though these features do not always provide full protection. We investigated how nest microhabitat characteristics and prey availability modulate nest survival in tundra birds that select pond and lake islets as breeding sites. Over four summers, we analyzed the survival of 132 cackling goose and 55 glaucous gull nests located on islets or on pond and lake shores within a 150 km2 area occupied by a snow goose colony on Bylot Island, Nunavut, Canada. We also analyzed survival of 537 artificial nests deployed over three summers. We found that islets act as partial prey refuges, with higher nest survival rates on islets than on pond and lake shores. Nest survival generally increased with islet distance from shore, but we found little evidence of this effect for cackling geese and glaucous gulls, which avoided nesting on islets near shore. Moreover, water depth surrounding islets had little to no influence for any nest type. Nest mortality was much higher in a year with relatively low snow goose nest density, suggesting a short-term positive indirect effect of this colonial nesting bird on species nesting on islets. Since the arctic fox was virtually the sole predator of artificial nests, our findings indicate that annual variation in nest survival on islets were driven by a shift in fox foraging behavior in response to changes in prey availability across the landscape. Our study, which integrates multi-year monitoring and field experiments, highlights the interplay between microhabitat selection and predator-multi-prey dynamics in the arctic tundra.

ecology↗

bioRxiv2025

Timing matters: phenological constraints and predation shape Arctic community structure

Top-down and bottom-up controls of animal populations are key elements of niche and coexistence theories, but there is still little empirical evidence on how these forces determine species distribution and community assemblies. In Arctic ecosystems, spring snowmelt sets the timing and duration of the snow-free period, thereby controlling food availability, while predation often imposes additional constraints on prey species. The relative importance of these abiotic and biotic filters on distribution is also susceptible to vary with body size. Using 10 years of high-resolution data on all major members of an Arctic vertebrate community and their shared predator, we tested how snowmelt timing interacts with predation to shape species occurrence and community structure. Species occurrence declined with later snowmelt dates, with larger-bodied species being particularly constrained by short snow-free periods. Predation further modulated species occurrence, with responses varying according to body mass. Our findings highlight the combined influence of the phenology of food availability and predation as important filters shaping local community structure. Building on species contrasted responses, we propose a conceptual framework for how phenological constraints and predation jointly shape community assembly in highly seasonal environments.

ecology↗

bioRxiv2022

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1.

Muscle weakness and atrophy are clinical hallmarks of myotonic dystrophy type 1 (DM1). Muscle stem cells, which contribute to skeletal muscle growth and repair, are also affected in this disease. However, the molecular mechanisms leading to this defective activity and the impact on the disease severity are still elusive. Here, we explored through an unbiased approach the molecular signature leading to myogenic cell defects in DM1. Single cell RNAseq data revealed the presence of a specific subset of DM1 myogenic cells expressing a senescence signature, characterized by the high expression of genes related to senescence-associated secretory phenotype (SASP). This profile was confirmed using different senescence markers in vitro and in situ. Accumulation of intranuclear RNA foci in senescent cells, suggest that RNA-mediated toxicity contribute to senescence induction. High expression of IL-6, a prominent SASP cytokine, in the serum of DM1 patients was identified as a biomarker correlating with muscle weakness and functional capacity limitations. Drug screening revealed that the BCL-XL inhibitor (A1155463), a senolytic drug, can specifically target senescent DM1 myoblasts to induce their apoptosis and reduce their SASP. Removal of senescent cells re-established the myogenic function of the non-senescent DM1 myoblasts, which displayed improved proliferation and differentiation capacity in vitro; and enhanced engraftment following transplantation in vivo. Altogether this study presents a well-defined senescent molecular signature in DM1 untangling part of the pathological mechanisms observed in the disease; additionally, we demonstrate the therapeutic potential of targeting these defective cells with senolytics to restore myogenesis.

cell biology↗

bioRxiv2020

The predator activity landscape predicts the anti-predator behavior and distribution of prey in a tundra community

Predation shapes communities through consumptive and non-consumptive effects, where in the latter prey respond to perceived predation risk through risk management strategies occurring at different spatial and temporal scales. The landscape of fear concept is useful to better understand how predation risk affects prey behavioral decisions and distribution, and more generally the spatial dimension of predator-prey relationships. We assessed the effects of the predation risk landscape in a terrestrial Arctic community, where arctic fox is the main predator of ground-nesting bird species. Using high frequency GPS data, we developed a predator activity landscape resulting from fox space use patterns, and validated with an artificial prey experiment that it generated a predation risk landscape. We then investigated the effects of the fox activity landscape on multiple prey, by assessing the anti-predator behavior of a primary prey (snow goose) and the nest distribution of several incidental prey. Areas highly used by foxes were associated with a stronger level of nest defense by snow geese. We further found a lower probability of occurrence of incidental prey nests in areas highly used by foxes, but only for species nesting in habitats easily accessible to foxes. Species nesting in refuges consisting of micro-habitats limiting fox accessibility, like islets, did not respond to the fox activity landscape. Consistent with the scale of the fox activity landscape, this result reflected the capacity of refuges to allow bird nesting without regard to predation risk in the surrounding area. We demonstrated the value of using predator space use patterns to infer spatial variation in predation risk and better understand its effects on prey in landscape of fear studies. We also exposed the diversity of prey risk management strategies, hence refining our understanding of the mechanisms driving species distribution and community structure.

ecology↗