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Beaudoin, M.

Publications and source records attributed to Beaudoin, M..

3 recordsLinked to original sources

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↗

Pooled CRISPR screens identify genes and non-coding genomic regions that regulate red blood cell density

Genome-wide association studies have identified >1,000 loci associated with clinically important red blood cell (RBC) traits, such as hemoglobin concentration and cell volume. However, few of these associations have been characterized at the molecular level such that most causal genes and variants remain elusive. Here, we performed pooled CRISPR screens in an erythroid cell line to identify genes and regulatory non-coding sequences that control RBC density. We perturbed 556 candidate genes and genomic sequences near 2,114 GWAS variants. We used a density gradient to detect the impact of these CRISPR perturbations on cell density. After validation, we found 17 genes and 13 regions near GWAS variants that regulate cell density. Some of these genes have previously been implicated in RBC biology (e.g. ATP2B4, CCND3, EPOR) although many are novel (e.g. CHTF8, CTU2, DNASE2). We confirmed that deletions in the osmotic stress response kinase gene OXSR1 increase cell density, and a phosphoproteome analysis in OXSR1-depleted cells indicated that this phenotype is accompanied with a dephosphorylation of the upstream kinase WNK1 and the downstream target KCC3 (SLC12A6). We also combined CRISPR perturbations and RNA-sequencing to show how a non-coding genomic sequence near rs13255015 regulates the expression of the transcription factor ZFAT in cis and SLC4A1 in trans. SLC4A1 encodes Band3, a known regulator of RBC hydration and volume. Our results suggest experimental strategies to characterize GWAS findings and provide new molecular insights into the regulation of complex RBC traits.

genomics↗

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

Genome-wide association studies have identified 161 genetic variants associated with coronary artery disease (CAD), but the causal genes and biological pathways remain unknown at most loci. Here, we used CRISPR knockout, inhibition and activation to target 1998 variants at 83 CAD loci to assess their effect on six vascular endothelial cell phenotypes (E-selectin, ICAM1, VCAM1, nitric oxide, reactive oxygen species, calcium signalling). We identified 42 significant variants located within 26 CAD loci. Detailed characterization of the RNA helicase DHX38 and CRISPR activation at the FURIN/FES, CCDC92/ZNF664 and CNNM2 loci revealed a strong effect on vascular endothelial cell senescence.

genomics↗