An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins.

Enteropathogenic Escherichia coli (EPEC) is an attaching and effacing (A/E) human pathogen that causes diarrhea during acute infection, and it can also sustain asymptomatic colonization. A/E E. coli depletes host cell DNA mismatch repair (MMR) proteins in colonic cell lines and has been detected in colorectal cancer (CRC) patients. However, until now, a direct link between infection and host mutagenesis has not been fully demonstrated. Here we show that the EPEC-secreted effector protein EspF is critical for complete EPEC-induced depletion of MMR proteins. The mechanism of EspF activity on MMR protein was posttranscriptional and dependent on EspF mitochondrial targeting. EPEC infection also induced EspF-independent elevation of host reactive oxygen species levels. Moreover, EPEC infection significantly increased spontaneous mutation frequency in host cells, and this effect was dependent on mitochondrially targeted EspF. Taken together, these results support the hypothesis that A/E E. coli can promote colorectal carcinogenesis in humans

Metabolic regulation by p53 family members

The function of p53 is best understood in response to genotoxic stress, but increasing evidence suggests that p53 also plays a key role in the regulation of metabolic homeostasis. p53 and its family members directly influence various metabolic pathways, enabling cells to respond to metabolic stress. These functions are likely to be important for restraining the development of cancer but could also have a profound effect on the development of metabolic diseases, including diabetes. A better understanding of the metabolic functions of p53 family members may aid in the identification of therapeutic targets and reveal novel uses for p53-modulating drugs

Competition and bistability of ordered undulations and undulation chaos in inclined layer convection

Experimental and theoretical investigations of undulation patterns in high-pressure, inclined layer gas convection at a Prandtl number near unity are reported. Particular focus is given to the competition between the spatiotemporal chaotic state of undulation chaos and stationary patterns of ordered undulations. In experiments a competition and bistability between the two states is observed, with ordered undulations most prevalent at higher Rayleigh number. The spectral pattern entropy, spatial correlation lengths, and defect statistics are used to characterize the competing states. The experiments are complemented by a theoretical analysis of the Oberbeck-Boussinesq equations. The stability region of the ordered undulation as a function of their wavevectors and the Rayleigh number is obtained with Galerkin techniques. In addition, direct numerical simulations are used to investigate the spatiotemporal dynamics. In the simulations both ordered undulations and undulation chaos were observed dependent on initial conditions. Experiment and theory are found to agree well.Comment: Reduced-resolution figure