« Premier de la classe » : discours sur l’équité liés aux nominations des directeurs de département dans une école de médecine canadienne

Purpose: Equitable appointments of departmental leaders in medical schools have lagged behind other Equity, Diversity, and Inclusion (EDI) advancements. The purpose of this research was to 1) analyze how policy documents communicate changing ideas of EDI, employment equity, and departmental leadership; and 2) investigate department heads’ perspectives on EDI policies and practices. Methods: We conducted a critical discourse analysis to examine underlying assumptions shaping EDI and departmental leadership in one Canadian medical school. We created and analyzed a textual archive of EDI documents (n = 17, 107 pages) and in-depth interviews with past (n = 6) and current (n = 12) department heads (830 minutes; 177 pages). Results: Documents framed EDI as: a legal requirement; an aspiration; and historical reparation. In interviews, participants framed EDI as: affirmative action; relationships; numerical representation; and relinquishing privilege. We noted inconsistent definitions of equity-deserving groups. Conclusions: Change is slowly happening, with emerging awareness of white privilege, allyship, co-conspiracy, and the minority tax. However, there is more urgent work to be done. This work requires an intersectional lens. Centering the voices, and taking cues from, equity-deserving leaders and scholars, will help ensure that EDI pathways, such as those used to cultivate department leaders, are more inclusive, effective, and aligned with intentions.Objectif : La nomination des directeurs de département dans les facultés de médecine n’a pas connu les mêmes avancements en matière d’équité, de diversité et d’inclusion (EDI) que d’autres domaines. L’objectif de cette recherche était 1) d’analyser dans quelle mesure les documents de politique reflètent l’évolution des idées liées à l’EDI, à l’équité en matière d’emploi et au leadership départemental; et 2) de sonder le point de vue des directeurs de département sur les politiques et les pratiques en matière d’EDI. Méthodes : Empruntant le cadre d’analyse critique du discours, nous avons examiné les conceptions sous-jacentes qui façonnent l’EDI et le leadership des DD dans une faculté de médecine canadienne. Nous avons créé et analysé un corpus de documents relatifs à l’EDI (n=17, 107 pages) et d’entrevues approfondies avec des directeurs de département anciens (n=6) et actuels (n=12) (830 minutes; 177 pages). Résultats : Les documents décrivent l’EDI comme une obligation légale, une aspiration et une réparation historique. Lors des entretiens, pour définir l’EDI, les participants ont évoqué l’action positive, les relations, la représentation numérique et l’abandon des privilèges. Nous avons noté des incohérences quant à la définition de « groupe privé d’équité ». Conclusions : Le changement s’opère lentement, avec une prise de conscience des notions de privilège blanc, d’allié, de complicité et de fardeau – celui assumé par les groupes minoritaires pour mener le changement (« taxe pour les minorités »). Cependant, il y a un travail plus urgent à accomplir. Ce travail nécessite une perspective intersectionnelle. Le fait d’écouter les leaders et les universitaires en quête d’équité et de leur accorder une place centrale fera en sorte que les voies de l’EDI, comme celles empruntées pour cultiver le leadership dans les départements, soient plus inclusives, plus efficaces et plus en adéquation avec les objectifs

Kalirin Decreases Bone Mass Through Effects in Both Osteoclasts and Osteoblasts

poster abstractBone homeostasis is maintained by the balance between osteoclasts which degrade bone and osteoblasts, which form new bone. When the activity of either of these cells is dysregulated, bone loss can ensue, leading to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. The activity of osteoclasts and osteoblasts is regulated by local and systemic factors, as well as by key signaling proteins expressed in these cells. Kalirin is a novel GTP-exchange factor protein that plays a role in signaling pathways leading to cytoskeletal remodeling and dendritic spine formation in neurons, but its function in other cells is unknown. Western blotting and real time PCR confirmed that Kalirin is expressed in osteoclasts and osteoblasts, suggesting it may play a role in regulating bone cell function and bone mass. We used micro-CT to examine the bone phenotype of 14 week old female mice lacking Kalirin in all tissues (Kal-KO). Kal-KO mice exhibited a 40% lower trabecular bone volume in the distal femur compared to wild-type (WT) mice (n=9/group, p<0.05). We next quantified osteoclasts in histological sections by counting multinucleated cells expressing tartrate-resistant acid phosphatase (TRAP), a marker of mature osteoclasts. We found 48% higher osteoclast surface/bone surface in trabecular bone of Kal-KO mice, compared to WT mice (n=6/group, p<0.05). Osteoclast differentiation is controlled by osteoblasts, which secrete receptor activator of NF-kB ligand (RANKL), macrophage colony stimulating factor (MCSF) and osteoprotegerin (OPG), a decoy receptor for RANKL. We examined if Kalirin could regulate osteoclast differentiation in vitro. Osteoclasts were generated from the bone marrow of WT or Kal-KO mice by incubation with RANKL and MCSF for 7 days, and TRAP+ multinucleated cells were counted. Consistent with our in vivo studies, osteoclast number was significantly higher in cultures from Kal-KO mice, compared to WT mice. We next examined if Kalirin altered the ratio of secreted RANKL and OPG secreted by osteoblasts. Osteoblasts were generated from the calvaria of 2 day old neonates and the level of secreted RANKL and OPG in conditioned media was quantified by ELISA. Consistent with increased osteoclast differentiation, we found a higher RANKL/OPG ratio in conditioned media from Kal-KO osteoblasts, compared to WT cells. These data confirm a role for Kalirin in the regulation of trabecular bone mass through effects in both osteoclasts and osteoblasts

Saturation of SERCA's lipid annulus may protect against its thermal inactivation.

The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca2+ into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybean oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting.Analyses supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to PJL. The in vivo portion of the study was funded by start-up funding from Brock University to WEW. VAF was supported through a Canadian Institutes of Health Research (CIHR) Doctoral Award; NT and PM were both supported through CIHR Master's Awards; LC was supported through an Ontario Graduate Scholarship. WEW holds a Canada Research Chair in Bone and Muscle Development

Isolation of bacterial extrachromosomal DNA from human dental plaque associated with periodontal disease,using transposonaided capture (TRACA)

The human oral cavity is host to a complex microbial community estimated to comprise > 700 bacterial species, of which at least half are thought to be not yet cultivable in vitro. To investigate the plasmids present in this community, we used a transposon-aided capture system, which allowed the isolation of plasmids from human oral supra- and subgingival plaque samples. Thirty-two novel plasmids and a circular molecule that could be an integrase-generated circular intermediate were isolated

Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse

The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β peptide and for its role in Alzheimer's disease. Much less is known, however, on the physiological roles of APP in the development and plasticity of the central nervous system. We have used phage display of a peptide library to identify high-affinity ligands of purified recombinant human sAPPα695 (the soluble, secreted ectodomain from the main neuronal APP isoform). Two peptides thus selected exhibited significant homologies with the conserved extracellular domain of several members of the semaphorin (Sema) family of axon guidance proteins. We show that sAPPα695 binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPα695 inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (Kd≤8·10−9 M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPα binding and its inhibitory action on Sema3A function. These two peptides are comprised within a domain previously shown to be involved in binding of Sema3A to its cellular receptor, suggesting a competitive mechanism by which sAPPα modulates the biological action of semaphorins