Maintaining Integrity Under Stress:Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

The Gram-negative bacterial envelope is an essential interface between the intracellular and harsh extracellular environment. Envelope stress responses (ESRs) are crucial to the maintenance of this barrier and function to detect and respond to perturbations in the envelope, caused by environmental stresses. Pathogenic bacteria are exposed to an array of challenging and stressful conditions during their lifecycle and, in particular, during infection of a host. As such, maintenance of envelope homeostasis is essential to their ability to successfully cause infection. This review will discuss our current understanding of the σE- and Cpx-regulated ESRs, with a specific focus on their role in the virulence of a number of model pathogens

Loss of Transgelin in Breast and Colon Tumors and in RIE-1 Cells by Ras Deregulation of Gene Expression through Raf-independent Pathways

Activated Ras but not Raf can transform RIE-1 and other epithelial cells, indicating the critical importance of Raf-independent effector function in Ras transformation of epithelial cells. To elucidate the nature of these Raf-independent activities, we utilized representational difference analysis to identify genes aberrantly expressed by Ras through Raf-independent mechanisms in RIE-1 cells. We identified a total of 22 genes, both known and novel, whose expression was either activated or abolished by Ras but not Raf. The genes up-regulated encode proteins involved in protein or DNA synthesis, regulation of protease activity, or ligand binding, whereas those genes down-regulated encode actin cytoskeletal-, extracellular matrix-, and gap junction-associated proteins, and transmembrane receptor- or cytokine-like proteins. These results suggest that a key function of Raf-independent signaling involves deregulation of gene expression. We further characterized transgelin as a gene whose expression was abolished by Ras. Transgelin was identified previously as a protein whose expression was lost in virally transformed cell lines. We show that this loss is regulated at the level of gene expression and that both Raf-dependent and Raf-independent pathways are required to cause Ras down-regulation of transgelin in RIE-1 cells, whereas Raf alone is sufficient to cause its loss in NIH 3T3 fibroblasts. We also found that Ras-dependent and Ras-independent mechanisms can cause the down-regulation of transgelin in human breast and colon carcinoma cells lines and patient-derived tumor samples. We conclude that loss of transgelin gene expression may be an important early event in tumor progression and a diagnostic marker for breast and colon cancer development

Summation formulas associated with a class of Dirichlet series

The Poisson summation formula, which gives, under suitable conditions on f(x), and expression for sums of the form ^(n_2)Σ_(n=n_1) f(n) 1 ≤ n_1 < n_2 ≤ ∞ can be derived from the functional equation for the Riemann zeta-function (s). In this thesis a class of Dirichlet series is defined whose members have properties analogous to those of s(s); in particular, each series in the class, written in the form Ø(s) = ^∞Σ_(n=1) a(n) λ ^(-s)_n defines a meromorphic function Ø(s) which satisfies a relation analogous to the functional equation of s(s). From this relation an identity for sum of the form Σ_(^λn^(≤x) a(n) (x - λ_n)^q is derived. This identity in turn leads, in a quite simple fashion, to summation formulas which give expressions for sums of the form ^(n_2)Σ_(n=n_1) a(n) f(λ_n) 1 ≤ n_1 ≤ n_2 The summation formulas thus derived include the Poisson and other well-known summation formulas as special cases and in addition embrace many expressions that are new. The formulas are not only of interest in themselves, but also provide a tool for investigating many problems that arise in analytic number theory