Recent Findings Regarding Maintenance of Enzootic Variants of Yersinia pestis in Sylvatic Reservoirs and Their Significance in the Evolution of Epidemic Plague

Despite the widespread presence of bubonic plague in sylvatic reservoirs throughout the world, the causative agent (Yersinia pestis) evolved in its present form within the last 20,000 years from enteropathogenic Yersinia pseudotuberculosis. Comparison of the genomes from the two species revealed that Y. pestis possesses only a few unique plasmid-encoded genes that contribute to acute disease, whereas this organism has lost about 13% of the chromosomal genes that remain active in Y. pseudotuberculosis. These losses reflect readily detectable additions, deletions, transpositions, inversions, and acquisition of about 70 insertion sequence (IS) inserts, none of which are likely to promote increased virulence. In contrast, major enzymes of intermediary metabolism, including glucose 6-phosphate dehydrogenase (Zwf ) and aspartase, are present but not catalytically functional due to the presence of missense mutations. The latter are generally not detectable by the technology of bioinformatics and, in the case of Y. pestis, result in radical changes in the metabolic flow of carbon. As an important consequence, plague bacilli exhibit a stringent low-calcium response characterized by conversion of L-glutamate (and metabolically related amino acids) to L-aspartate with secretion of the latter into supernatant fluid at 37°C in culture media containing Na+ but lacking added Ca2+. This phenomenon also occurs in vivo and likely adversely affects the bioenergetics of host amino acid pools. Curiously, aspartase is functional in all tested enzootic (pestoides) strains of Y. pestis. These isolates are typically restricted to the ancient plague reservoirs of Central Asia and Africa and are fully virulent in members of the rodent Superfamily Muroidea but avirulent in guinea pigs and man. The implications of these findings for the distribution and ecology of Y. pestis could be significant

Reproductive factors and hormone use and risk of adult gliomas

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n=619) and controls (n=650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ years old versus 12–13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02 –1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11–2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53–0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37–0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use are needed to confirm findings