Investing in success: student experiences in a structured, decelerated preclinical medical school curriculum.

PURPOSE: Many students in the Michigan State University College of Human Medicine (CHM) are non-traditional with unique needs and experiences. To meet these needs, in 1988 CHM developed a structured Extended Curriculum Program (ECP), which allows students to take longer than 2 years to complete the preclinical curriculum. This work examined the reasons why students extended their programs, their perceptions of that experience, and the outcome with respect to satisfaction and success in their careers after graduation. METHODS: The analysis used data from the college database, follow-up surveys of residency directors and graduates, surveys of graduates who extended, and the AMA Physician Masterfile. RESULTS: Graduates who responded to the survey were evenly split between those who extended for academic reasons and those who extended for other reasons. Although feelings about extending were mixed at the time of extension, nearly all respondents agreed that extending was the right decision in the long run. Extended students continued to face academic challenges having lower basic science averages, lower USMLE Step 1 and 2 first attempt pass rates, and more instances of repeated clerkships compared to those who did not extend, however, most were able to secure a residency in the specialty they desired and had comparable career satisfaction ratings. CONCLUSIONS: The ECP allows some students to complete medical school who otherwise may not have been able to do so. This analysis has provided valuable information that was used to improve the program, allowing CHM to continue its mission of training a diverse set of students to be exemplary physicians.

Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase from Lactobacillus gasseri.

Enolases are highly conserved metalloenzymes ubiquitous to cellular metabolism. While these enzymes share a large degree of sequence and structural similarity, they have been shown to possess a wide range of moonlighting functions. Recent studies showed that an enolase from Lactobacillus gasseri impedes the ability of Neisseria gonorrhoeae to adhere to epithelial cells. We present the crystal structure of this enolase, the first from Lactobacillus, with one of its Mg(2+) cofactors. Determined using molecular replacement to 2.08Å, the structure has a flexible and surface exposed catalytic loop containing lysines, and may play a role in the inhibitory function.

Expression, purification, crystallization and preliminary X-ray studies of Lactobacillus jensenii enolase.

Recombinant Lactobacillus jensenii enolase fused to a C-terminal noncleavable His tag was expressed in Escherichia coli, purified and crystallized by sitting-drop vapor diffusion. A complete data set was collected to 3.25 A resolution. The crystals belonged to space group I4, with unit-cell parameters a=b=145.31, c=99.79 A. There were two protein subunits in the asymmetric unit, which gave a Matthews coefficient VM of 2.8 A3 Da(-1), corresponding to 55.2% solvent content.

Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase.

It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6-phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not detectable in epidemic Y. pestis due to missense mutations (substitution of proline for serine at amino position 155 of Zwf and leucine for valine at position 363 of AspA). In this study, functional Zwf was found in pestoides strains E, F and G but not seven other enzootic isolates; enzymic activity was associated with retention of serine at amino acid position 155. Essentially, full AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity occurred in strains Angola and A16, which contained phenylalanine at this position. The kcat but not Km of purified AspA from strain Angola was significantly reduced. In this context, aspA of the recently described attenuated enzootic microtus biovar encodes active valine at position 363, further indicating that functional AspA is a biomarker for avirulence of Y. pestis in man.

Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery.

OBJECTIVE: To assess relations among midpregnancy vaginal defensin levels, a component of the host innate immune response, bacterial vaginosis, and risk of preterm delivery. These relations are compared across race groups because previous studies have repeatedly shown that the prevalence of bacterial vaginosis and the risk of preterm delivery are greater in African-American women compared with that in white women. METHODS: Data are from a prospective study that enrolled pregnant women from 52 clinics in five Michigan communities. In the study subcohort, defensins (human neutrophil peptides 1, 2 and 3) and bacterial vaginosis (Nugent criteria) were measured in vaginal fluid collected at enrollment (15th through 27th week of pregnancy) from 1,031 non-Hispanic white and African-American women (787 term, 244 preterm). Preterm deliveries were categorized by clinical circumstances, ie, spontaneous and medically indicated. RESULTS: Among African Americans, vaginal human neutrophil peptides 1-3 levels greater than or equal to the median were associated with bacterial vaginosis and specifically with spontaneous preterm delivery only (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.3). Once African-American women were stratified by human neutrophil peptide 1-3 levels, bacterial vaginosis added nothing to the prediction of spontaneous preterm delivery risk. None of the above associations were observed in non-Hispanic whites. CONCLUSION: The relations among human neutrophil peptide 1-3 levels, bacterial vaginosis, and preterm delivery vary by race group. In African Americans, midpregnancy human neutrophil peptide 1-3 levels were more informative to preterm delivery risk than was bacterial vaginosis, suggesting an important role for host response. In addition, elevated human neutrophil peptide 1-3 levels may be a marker for particular high-risk vaginal milieus that are not distinguished by the current bacterial vaginosis Nugent scoring system.

A missense mutation causes aspartase deficiency in Yersinia pestis.

It is established that cells of Yersinia pestis, the causative agent of bubonic plague, excrete l-aspartic acid at the expense of exogenous l-glutamic acid during expression of the low-calcium response. Results of enzymic analysis provided here suggest that a previously defined deficiency of aspartase (AspA) accounts for this phenomenon rather than an elevated oxaloacetate pool. The only known distinction between most sequenced isolates of aspA from Y. pestis and the active gene in Yersinia pseudotuberculosis (the immediate progenitor of Y. pestis) is a single base transversion (G.C-->T.A) causing replacement of leucine (encoded by UUG) for valine (encoded by GUG) at amino acid position 363. The gene from Y. pestis KIM possesses a unique second transversion (G.C-->T.A) at amino acid 146 causing substitution of aspartic acid (encoded by GAU) with tyrosine (encoded by UAU). We show in this study that Y. pestis expresses aspA as cross-reacting immunological material (CRIM). Functional and inactive aspA of Y. pseudotuberculosis PB1 and Y. pestis KIM, respectively, were then cloned and expressed in AspA-deficient Escherichia coli. After purification to near homogeneity, the products were subjected to biochemical analysis and found to exhibit similar secondary, tertiary and quaternary (tetrameric) structures as well as comparable Michaelis constants for l-aspartic acid. However, the k(cat) of the Y. pestis CRIM of strain KIM is only about 0.1 % of that determined for the active AspA of Y. pseudotuberculosis. Return of valine for leucine at position 363 of the Y. pestis enzyme restored normal turnover (k(cat) 86+/-2 s(-1)) provided that the amino acid substitution at position 146 was also reversed. These observations have important implications for understanding the nature of the stringent low-calcium response of Y. pestis and its role in promoting acute disease.

Two ABC transporter operons and the antimicrobial resistance gene mtrF are pilT responsive in Neisseria gonorrhoeae.

Retraction of type IV pili is mediated by PilT. We show that loss of pilT function leads to upregulation of mtrF (multiple transferable resistance) and two operons encoding putative ABC transporters in Neisseria gonorrhoeae MS11. This effect occurs indirectly through the transcriptional regulator FarR, which until now has been shown to regulate only farAB. L-Glutamine can reverse pilT downregulation of the ABC transporter operons and mtrF.