32 research outputs found

    Supporting Indigenous Students: A Critical Analysis of the Sociocultural Context of Nursing Education

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    The purpose of this study was to critically examine the sociocultural context of nursing education as an institution. Using a postcolonial feminist theoretical framework and institutional ethnography, I illuminated the institutional complex of nursing education. This study addressed the following research questions: 1) How do practices, programs, and policies coordinate social relations within the institution of nursing education; and 2) How are Indigenous students’ everyday lives shaped by the institution of nursing education? Multiple methods were used to collect data, including: interviews, observations, and text analysis. Interviews were conducted with students, educators, and administrators and others involved in nursing education. Observations were conducted both formally, during interviews and meetings and informally, during my daily work within nursing education. Texts were collected to further explicate the institutional complex. The findings from this study revealed that race and class ruled the institution. Analysis exposed two irreconcilable social relations: Identifying as Indigenous and Identifying as a Nurse, that were central work processes within nursing education. The intersection of race and class was organized around Cultural Competence that was prevalent throughout institutional discourse. Cultural competence reproduced colonial ideology that provided the basis for dominant knowledge and shaped inclusionary/exclusionary practices. Thus, idealized practices that were aimed at the inclusion of Indigenous students ran contrary to intentions, as students were socially stratified based upon race and class relations. The findings illuminate the need to cultivate additional attentiveness and action related to social inequities within nursing education. Recommendations have been made related to education, policy, and research

    Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

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    To understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Therefore, to generate new insights into gene–environment interactions and complex behaviour, we examined the influence of variable prenatal stress (PNS) on two mouse lines with mutations in synaptosomal-associated protein of 25 kDa (Snap-25): the blind-drunk (Bdr) point mutant and heterozygous Snap-25 knockout mice. Neonatal development was analysed in addition to an assessment of adult behavioural phenotypes relevant to the psychotic, cognitive and negative aspects of schizophrenia. These data show that PNS influenced specific anxiety-related behaviour in all animals. In addition, sensorimotor gating deficits previously noted in Bdr mutants were markedly enhanced by PNS; significantly, these effects could be reversed with the application of anti-psychotic drugs. Moreover, social interaction abnormalities were observed only in Bdr animals from stressed dams but not in wild-type littermates or mutants from non-stressed mothers. These results show for the first time that combining a synaptic mouse point mutant with a controlled prenatal stressor paradigm produces both modified and previously unseen phenotypes, generating new insights into the interactions between genetics and the environment relevant to the study of psychiatric disease

    Rational Design of Protein Stability: Effect of (2S,4R)-4-Fluoroproline on the Stability and Folding Pathway of Ubiquitin

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    BACKGROUND: Many strategies have been employed to increase the conformational stability of proteins. The use of 4-substituted proline analogs capable to induce pre-organization in target proteins is an attractive tool to deliver an additional conformational stability without perturbing the overall protein structure. Both, peptides and proteins containing 4-fluorinated proline derivatives can be stabilized by forcing the pyrrolidine ring in its favored puckering conformation. The fluorinated pyrrolidine rings of proline can preferably stabilize either a C(γ)-exo or a C(γ)-endo ring pucker in dependence of proline chirality (4R/4S) in a complex protein structure. To examine whether this rational strategy can be generally used for protein stabilization, we have chosen human ubiquitin as a model protein which contains three proline residues displaying C(γ)-exo puckering. METHODOLOGY/PRINCIPAL FINDINGS: While (2S,4R)-4-fluoroproline ((4R)-FPro) containing ubiquitinin can be expressed in related auxotrophic Escherichia coli strain, all attempts to incorporate (2S,4S)-4-fluoroproline ((4S)-FPro) failed. Our results indicate that (4R)-FPro is favoring the C(γ)-exo conformation present in the wild type structure and stabilizes the protein structure due to a pre-organization effect. This was confirmed by thermal and guanidinium chloride-induced denaturation profile analyses, where we observed an increase in stability of -4.71 kJ·mol(-1) in the case of (4R)-FPro containing ubiquitin ((4R)-FPro-ub) compared to wild type ubiquitin (wt-ub). Expectedly, activity assays revealed that (4R)-FPro-ub retained the full biological activity compared to wt-ub. CONCLUSIONS/SIGNIFICANCE: The results fully confirm the general applicability of incorporating fluoroproline derivatives for improving protein stability. In general, a rational design strategy that enforces the natural occurring proline puckering conformation can be used to stabilize the desired target protein
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