Marie-Ève Gagné

Effect of mutations K97A and E128A on RNA binding and self assembly of papaya mosaic potexvirus coat protein

Papaya mosaic potexvirus (PapMV) coat protein (CP) was expressed (CPΔN5) in Escherichia coli and showed to self assemble into nucleocapsid like particles (NLPs). Twenty per cent of the purified protein was found as NLPs of 50 nm in length and 80% was found as a multimer of 450 kDa (20 subunits) arranged in a disk. Two mutants in the RNA binding domain of the PapMV CP, K97A and E128A showed interesting properties. The proteins of both mutants could be easily purified and CD spectra of these proteins showed secondary and tertiary structures similar to the WT protein. The mutant K97A was unable to self assemble and bind RNA. On the contrary, the mutant E128A showed an improved affinity for RNA and self assembled more efficiently in NLPs. E128A NLPs were longer (150 nm) than the recombinant CPΔN5 and 100% percent of the protein was found as NLPs in bacteria. E128A NLPs were more resistant to digestion by trypsin than the CPΔN5 but were more sensitive to denaturation by heat. We discuss the possible role of K97 and E128 in the assembly of PapMV.

Using dual task walking as an aid to assess executive dysfunction ecologically in neurological populations: A narrative review

Within rehabilitation, clinical assessment plays a crucial role in diagnosis, prognostication and making decisions about return to function. The ecological validity of the assessment of executive dysfunction has become a particular focus in neuropsychology and is gaining interest in mobility research and neurological rehabilitation of acquired brain injury or degenerative neurological diseases. In this narrative review, we look at how the task of walking and the inseparable cognitive demands and interference of the surrounding environment are exploited in dual task walking (DTW) paradigms to expose executive dysfunction. While quite a number of studies and reviews have recently focused on the utility of DTW for gait assessment, particularly to assess fall risk, very little consideration has been given to the level of ecological validity required. This paper directly addresses this issue with discussion of evidence and lacunas related to task, personal and technological factors that should be addressed in order to exploit fully DTW paradigms as an ecological assessment tool.

Executive dysfunction following a mild traumatic brain injury revealed in early adolescence with locomotor-cognitive dual-tasks

Abstract Objective: To compare gait parameters between children in early adolescence (EA) with and without a mild traumatic brain injury (mTBI) during dual-task walking (DTW). Methods: Children in EA with mTBI (n = 14; six girls) were compared to those without (n = 13; five girls) while walking in different combinations of obstacle avoidance and cognitive dual-tasks. Gait speed and fluidity and their related dual-task costs (DTC) were analysed along with foot clearance and proximity to the obstacle. Results: No group effects were found for gait speed, proximity or clearance, but were found for fluidity DTC, specifically during the dual Stroop task and when crossing the deeper obstacle. There were also group differences for fluidity during the planning of obstacle avoidance for the narrow obstacle combined with the verbal fluency task and the deep obstacle with no cognitive task. Finally, gait fluidity showed group differences across unobstructed dual-task situations. Conclusions: Gait fluidity may be a more sensitive variable than gait speed for revealing executive dysfunction following mTBI in EA. Assessing DTW in level walking also seems to show a potential to reveal executive dysfunctions in this age group. These results provide direction for future research on clinical assessment using DTW post-mTBI in adolescents.

Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine

The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6-14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.

Correlates of cognitive functioning in independent elderly patients discharged home from the emergency department after a minor injury

BACKGROUND The objective of this study was to explore correlates of cognitive functioning of older adults visiting the emergency department (ED) after a minor injury. METHODS These results are derived from a large prospective study in three Canadian EDs. Participants were aged ≥ 65 years and independent in basic activities of daily living, visiting the ED for minor injuries and discharged home within 48 hours (those with known dementia, confusion, and delirium were excluded). They completed the Montreal Cognitive Assessment (MoCA). Potential correlates included sociodemographic and injury variables, and measures of psychological and physical health, social support, mobility, falls, and functional status. RESULTS Multivariate analyses revealed that male sex, age ≥ 85 years, higher depression scores, slower walking speed, and self-reported memory problems were significantly associated with lower baseline MoCA scores. CONCLUSIONS These characteristics could help ED professionals identify patients who might need additional cognitive evaluations or follow-ups after their passage through the ED. Obtaining information on these characteristics is potentially feasible in the ED context and could help professionals alter favorably elderlys trajectory of care. Since a significant proportion of elderly patients consulting at an ED have cognitive impairment, the ED is an opportunity to prevent functional and cognitive decline.

Obstacles à l’inclusion scolaire des enfants d’âge préscolaire ayant des besoins spéciaux

RésuméLe présent article vise d’abord à identifier les obstacles à l’inclusion scolaire de jeunes enfants ayant des besoins spéciaux. Par la suite, il propose de nouvelles stratégies pour préparer et soutenir les intervenants impliqués lors de la transition et de l’inclusion en milieu scolaire. Pour ce faire, treize personnes provenant de différents environments (parents, éducateurs en milieux de garde, enseignants, gestionnaires) ont participé à un groupe de discussion dirigée. Cette démarche a permis de préciser les différentes composantes d’un plan de transition.AbstractThis article first intends to identify the obstacles young children with special needs face when trying to integrate school. It also proposes new strategies to prepare and support the personnel involved during the transition and inclusion in the school setting. In order to do so, thirteen people from different environments (parents, care center educators, teachers, administrators) participated in a directed discussion group, which resulted in the detailing of a transition plan.ResumenEl presente artículo trata, en primer lugar, de identificar los obstáculos que enfrentan los niños con necesidades educativas especiales para integrarse a la vida escolar. Luego, propone nuevas estrategias para preparar y sostener a los educadores implicados en la transición y en la inregración escolar. Para su realización, trece personas provenientes de diferentes medios (padres, educadores de párvulos, profesores, administradores) participaron en un grupo de discusión dirigida, lo que permitió precisar los diferentes componentes de un plan de transición.