Biology subjects

Boucher, A.

Publications and source records attributed to Boucher, A..

3 recordsLinked to original sources

bioRxiv2023

Fucosylated glycoproteins and fucosylated glycolipids play opposing roles in cholera intoxication

Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout of B3GNT5, the enzyme required for synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. Knockout (KO) of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins, and leads to increased CT binding and intoxication. Knockout of B3GNT5 in B3GALT5 KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into molecular determinants regulating CT sensitivity of host cells.

biochemistry↗

bioRxiv2021

Snrpb, the gene mutated in CCMS, is haploinsufficient and required for proper morphogenesis and splicing

Heterozygous mutations in SNRPB, an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for Cerebrocostomandibular Syndrome (CCMS). We show that Snrpb heterozygous embryos arrest shortly after implantation. Additionally, heterozygous deletion of Snrpb in the developing brain and neural crest cells models craniofacial malformations found in CCMS, and results in death shortly after birth. RNAseq analysis of mutant heads prior to morphological defects revealed increased exon-skipping and intron-retention in association with increased 5 splice site strength. We found increased exon-skipping in negative regulators of the P53-pathway, increased levels of nuclear P53, P53-target genes. However, removing TrP53 in Snrpb heterozygous mutant neural crest cells did not completely rescue craniofacial development. We also found a small but significant increase in exon-skipping of several transcripts required for head and midface development, including Smad2 and Rere. Furthermore, mutant embryos exhibited ectopic or missing expression of Fgf8 and Shh, which are required to coordinate face and brain development. Thus, we propose that mis-splicing of transcripts that regulate P53-activity and craniofacial-specific genes both contribute to craniofacial malformations.

developmental biology↗

bioRxiv2018

Examining Academic Leaders work in implementing Competency-based Medical Education (CBME) using Organizational Learning Theory

ContextCompetency-based medical education (CBME) implementation is being carried out in many medical schools worldwide. Academic Leadership is a strategy where selected Faculty act to influence peers to adopt change. The Universite de Montreal medical school, has adopted this strategy to implement CBME.\n\nPurposeThis paper aims to describe the work of Academic Leaders in the process of CBME implementation and to explore relevance of the Nonaka and Toyama organizational learning theory to map implementation progress.\n\nMethodBecause knowledge creation model focuses on the relationships between leaders and social structures, embedded case study was selected. Diverse sampling method was used to select three departments: internal medicine, surgery and psychiatry, based on the number of CBME training activities. Data collection was at two intervals, two years apart. Semi-structured interviews (individual and group) were conducted with Department Heads and Academic Leaders. Thematic analysis was conducted on the 15 interview transcriptions.\n\nResultsAs implementation begins, Leaders critically revisit accepted teaching routines and develop a common conception of CBME. This enables leaders to communicate with a wider audience and work within existing committees and working groups where they \"break down\" CBME into practical concepts. This practical understanding, disseminated through Entrustable Professional Activities, enables observable change.\n\nConclusionLeaders roles evolved from an \"expert\" that disseminates knowledge about CBME through lectures, to a responsive and pragmatic supporting role by developing and writing practical tools in collaboration with peers and program directors.

scientific communication and education↗