The starvation-stress response (SSR) of Salmonella typhimurium includes gene products necessary for starvation avoidance, starvation survival and virulence for this bacterium. Numerous genetic loci induced during carbon-source starvation and required for the long-term-starvation survival of this bacterium have been identified. The SSR not only protects the cell against the adverse effects of long-term starvation but also provides cross-resistance to other environmental stresses, e.g. thermal challenge (55 mC) or acid-pH challenge (pH 28). One carbon-starvation-inducible lac fusion, designated stiA was previously reported to be a σ S -dependent SSR locus that is phosphatestarvation, nitrogen-starvation and H 2 O 2 inducible, positively regulated by (p)ppGpp in a relA-dependent manner, and negatively regulated by cAMP :cAMP receptor protein complex and OxyR. We have discovered through sequence analysis and subsequent biochemical analysis that the stiA ::lac fusion, and a similarly regulated lac fusion designated sti-99, lie at separate sites within the first gene (narZ) of an operon encoding a cryptic nitrate reductase (narZYWV) of unknown physiological function. In this study, it was demonstrated that narZ was negatively regulated by the global regulator Fnr during anaerobiosis. Interestingly, narZ(YWV) was required for carbonstarvation-inducible thermotolerance and acid tolerance. In addition, narZ expression was induced "20-fold intracellularly in Madin-Darby canine kidney epithelial cells and "16-fold in intracellular salts medium, which is believed to mimic the intracellular milieu. Also, a narZ1 knock-out mutation increased the LD 50 "10-fold for S. typhimurium SL1344 delivered orally in the mouse virulence model. Thus, the previously believed cryptic and constitutive narZYWV operon is in fact highly regulated by a complex network of environmental-stress signals and global regulatory functions, indicating a central role in the physiology of starved and stressed cells.

Pure invasive lobular carcinomas can present as a hyperechoic mass or with substantial hyperechoic component. All sonographic lesion characteristics should be evaluated and biopsy recommended when there are suspicious features, even in a lesion that is predominantly hyperechoic.

The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Rasmediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short-and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences.

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