Alterations to the protein profile of bladder carcinoma cell lines induced by plant extract MINA-05 in vitro.

Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile.

Divergence and redundancy of transport and metabolic rate-yield strategies in a single Escherichia coli population.

The energetic efficiency of nutrient uptake and conversion into biomass is a key factor in the ecological behavior of microorganisms. The constraints shaping the metabolic rate-yield trade-off in bacteria are not well understood. To examine whether metabolic rate-yield settings and physiological strategies evolve toward a particular optimum in a constant environment, we studied multiple Escherichia coli isolates evolving in a glucose-limited chemostat population.

Clonal adaptive radiation in a constant environment.

The evolution of new combinations of bacterial properties contributes to biodiversity and the emergence of new diseases. We investigated the capacity for bacterial divergence with a chemostat culture of Escherichia coli. A clonal population radiated into more than five phenotypic clusters within 26 days, with multiple variations in global regulation, metabolic strategies, surface properties, and nutrient permeability pathways.

Genotype-by-environment interactions influencing the emergence of rpoS mutations in Escherichia coli populations.

Polymorphisms in rpoS are common in Escherichia coli. rpoS status influences a trade-off between nutrition and stress resistance and hence fitness across different environments. To analyze the selective pressures acting on rpoS, measurement of glucose transport rates in rpoS+ and rpoS bacteria was used to estimate the role of F(nc), the fitness gain due to improved nutrient uptake, in the emergence of rpoS mutations in nutrient-limited chemostat cultures.

The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli growing under glucose limitation.

Escherichia coli changes its metabolism in response to environmental circumstances, and metabolic adaptations are evident in hungry bacteria growing slowly in glucose-limited chemostats. The role of isocitrate lyase (AceA) was examined in E. coli growing under glucose limitation.

The multifactorial influences of RpoS, Mlc and cAMP on ptsG expression under glucose-limited and anaerobic conditions.

The ptsG gene encodes the high-affinity glucose receptor component of the PEP:glucose phosphotransferase system. PtsG is the major glucose transporter in Escherichia coli under glucose-excess conditions but its regulation under glucose limitation or anaerobiosis is poorly defined. Using a ptsG-lacZ transcriptional fusion, ptsG expression was found to peak with low (micromolar) external glucose levels in glucose-limited chemostats, so PtsG is primed to contribute to glucose scavenging under hunger response conditions.

The influence of cellular physiology on the initiation of mutational pathways in Escherichia coli populations.

The factors affecting the direction of evolutionary pathways and the reproducibility of adaptive responses were investigated under closely related but non-identical conditions. Replicate chemostat cultures of Escherichia coli were compared when adapting to partial or severe glucose limitation. Four independent populations used a reproducible sequence of early mutational changes under both conditions, with rpoS mutations always occurring first before mgl.

Enrichment and elimination of mutY mutators in Escherichia coli populations.

The kinetics of mutator sweeps was followed in two independent populations of Escherichia coli grown for up to 350 generations in glucose-limited continuous culture. A rapid elevation of mutation rates was observed in both populations within 120-150 generations, as was apparent from major increases in the proportion of the populations with unselected mutations in fhuA. The increase in mutation rates was due to sweeps by mutY mutators.

Regulation of mutY and nature of mutator mutations in Escherichia coli populations under nutrient limitation.

Previous analysis of aerobic, glucose-limited continuous cultures of Escherichia coli revealed that G:C-to-T:A (G:C-->T:A) transversions were the most commonly occurring type of spontaneous mutation. One possible explanation for the preponderance of these mutations was that nutrient limitation repressed MutY-dependent DNA repair, resulting in increased proportions of G:C-->T:A transversions. The regulation of the mutY-dependent DNA repair system was therefore studied with a transcriptional mutY-lacZ fusion recombined into the chromosome.