RESUMEN
BACKGROUND: Given the importance of the selection process, many medical schools are reviewing their selection criteria. The traditional pathway for post-graduate medicine has been from science-based undergraduate degrees, however some programs are expanding their criteria. In this study we investigated academic success across all years and themes of the Deakin University medical degree, based on the type of degree undertaken prior to admission. We evaluated whether the traditional pathway of biomedical science into medicine should remain the undergraduate degree of choice, or whether other disciplines should be encouraged. METHODS: Data from 1159 students entering the degree from 2008 to 2016 was collected including undergraduate degree, grade point average (GPA), Graduate Medical Schools Admission Test (GAMSAT) score and academic outcomes during the 4 years of the degree. Z-scores were calculated for each assessment within each cohort and analysed using a one sample t-test to determine if they differed from the cohort average. Z-scores between groups were analysed by 1-way ANOVA with LSD post-hoc analysis correcting for multiple comparisons. RESULTS: The majority of students had Science (34.3%) or Biomedical Science (31.0%) backgrounds. 27.9% of students had a Health-related undergraduate degree with smaller numbers of students from Business (3.5%) and Humanities (3.4%) backgrounds. At entry, GPA and GAMSAT scores varied significantly with Biomedical Science and Science students having significantly higher scores than Health students. Health students consistently outperformed students from other disciplines in all themes while Biomedical Science students underperformed. CONCLUSIONS: Our data suggest that a Health-related undergraduate degree results in the best performance throughout medical school, whereas a Biomedical Science background is associated with lower performance. These findings challenge the traditional Biomedical Science pathway into medicine and suggest that a health background might be more favourable when determining the selection criteria for graduate entry into medicine.
Asunto(s)
Rendimiento Académico , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Educación de Pregrado en Medicina/métodos , Evaluación Educacional , Criterios de Admisión Escolar , Facultades de Medicina , EstudiantesRESUMEN
Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrhea in infants in developing countries. We have identified a functional type II secretion system (T2SS) in EPEC that is homologous to the pathway responsible for the secretion of heat-labile enterotoxin by enterotoxigenic E. coli. The wild-type EPEC T2SS was able to secrete a heat-labile enterotoxin reporter, but an isogenic T2SS mutant could not. We showed that the major substrate of the T2SS in EPEC is SslE, an outer membrane lipoprotein (formerly known as YghJ), and that a functional T2SS is essential for biofilm formation by EPEC. T2SS and SslE mutants were arrested at the microcolony stage of biofilm formation, suggesting that the T2SS is involved in the development of mature biofilms and that SslE is a dominant effector of biofilm development. Moreover, the T2SS was required for virulence, as infection of rabbits with a rabbit-specific EPEC strain carrying a mutation in either the T2SS or SslE resulted in significantly reduced intestinal colonization and milder disease.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Escherichia coli Enteropatógena/fisiología , Escherichia coli Enteropatógena/patogenicidad , Proteínas de Escherichia coli/metabolismo , Factores de Virulencia/metabolismo , Animales , Membrana Celular , Escherichia coli Enteropatógena/citología , Escherichia coli Enteropatógena/genética , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Mutación , Conejos , Especificidad por Sustrato , Virulencia , Factores de Virulencia/genéticaRESUMEN
The gene cluster gspCDEFGHIJKLM codes for various structural components of the type II secretion pathway which is responsible for the secretion of heat-labile enterotoxin by enterotoxigenic Escherichia coli (ETEC). In this work, we used a variety of molecular approaches to elucidate the transcriptional organization of the ETEC type II secretion system and to unravel the mechanisms by which the expression of these genes is controlled. We showed that the gspCDEFGHIJKLM cluster and three other upstream genes, yghJ, pppA, and yghG, are cotranscribed and that a promoter located in the upstream region of yghJ plays a major role in the expression of this 14-gene transcriptional unit. Transcription of the yghJ promoter was repressed 168-fold upon a temperature downshift from 37 degrees C to 22 degrees C. This temperature-induced repression was mediated by the global regulatory proteins H-NS and StpA. Deletion mutagenesis showed that the promoter region encompassing positions -321 to +301 relative to the start site of transcription of yghJ was required for full repression. The yghJ promoter region is predicted to be highly curved and bound H-NS or StpA directly. The binding of H-NS or StpA blocked transcription initiation by inhibiting promoter open complex formation. Unraveling the mechanisms of regulation of type II secretion by ETEC enhances our understanding of the pathogenesis of ETEC and other pathogenic varieties of E. coli.
Asunto(s)
Enterotoxinas/genética , Escherichia coli K12/genética , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos/genética , Familia de Multigenes/genética , Proteínas Bacterianas/genética , Secuencia de Bases , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Enterotoxinas/metabolismo , Escherichia coli K12/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Calor , Chaperonas Moleculares/metabolismo , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Proteínas Represoras/metabolismo , Transcripción GenéticaRESUMEN
The low-molecular-mass rhoptry complex of Plasmodium falciparum consists of three proteins, rhoptry-associated protein 1 (RAP1), RAP2, and RAP3. The genes encoding RAP1 and RAP2 are known; however, the RAP3 gene has not been identified. In this study we identify the RAP3 gene from the P. falciparum genome database and show that this protein is part of the low-molecular-mass rhoptry complex. Disruption of RAP3 demonstrated that it is not essential for merozoite invasion, probably because RAP2 can complement the loss of RAP3. RAP3 has homology with RAP2, and the genes are encoded on chromosome 5 in a head-to-tail fashion. Analysis of the genome databases has identified homologous genes in all Plasmodium spp., suggesting that this protein plays a role in merozoite invasion. The region surrounding the RAP3 homologue in the Plasmodium yoelii genome is syntenic with the same region in P. falciparum; however, there is a single gene. Phylogenetic comparison of the RAP2/3 protein family from Plasmodium spp. suggests that the RAP2/3 duplication occurred after divergence of these parasite species.
Asunto(s)
Genes Protozoarios , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , ADN Protozoario/genética , Eritrocitos/parasitología , Marcación de Gen , Genoma de Protozoos , Humanos , Datos de Secuencia Molecular , Filogenia , Plasmodium falciparum/patogenicidad , Homología de Secuencia de AminoácidoRESUMEN
Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.