Reduction of Vector and Axial--Vector Fields in a Bosonized Nambu--Jona--Lasinio Model

We derive the effective action for pseudoscalar mesons by integrating out vector and axial--vector collective fields in the generating functional of the bosonized NJL--model. The corresponding modifications of the nonlinear effective Lagrangian and the bosonized currents, arising at $O(p^4)$, are discussed.Comment: 30p. 1 fig. on reques

On the p4p^4--corrections to K→3πK \to 3\pi decay amplitudes in nonlinear and linear chiral models

The calculations of isotopic amplitudes and their results for the direct $CP$--violating charge asymmetry in $K^\pm \to 3\pi$ decays within the nonlinear and linear ($\sigma$--model) chiral Lagrangian approach are compared with each other. It is shown, that the latter, taking into account intermediate scalar resonances, does not reproduce the $p^4$--corrections of the nonlinear approach introduced by Gasser and Leutwyler, being saturated mainly by vector resonance exchange. The resulting differences concerning the $CP$ violation effect are traced in some detail.Comment: 14 page

Uropathogenic Escherichia coli virulence and innate immune responses during urinary tract infection

Urinary tract infections (UTI) are among the most common infectious diseases of humans and are the most common nosocomial infections in the developed world. It is estimated that 40-50% of women and 5% of men will develop a UTI in their lifetime, and UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenses each year in the USA. Uropathogenic Escherichia coli (UPEC) is the primary cause of UTI. This review presents an overview of recent discoveries related to the primary virulence factors of UPEC and major innate immune responses to infection of the lower urinary tract. New and emerging themes in UPEC research are discussed in the context of the interface between host and pathogen

Calculation of Heat-Kernel Coefficients and Usage of Computer Algebra

The calculation of heat-kernel coefficients with the classical DeWitt algorithm has been discussed. We present the explicit form of the coefficients up to $h_5$ in the general case and up to $h_7^{min}$ for the minimal parts. The results are compared with the expressions in other papers. A method to optimize the usage of memory for working with large expressions on universal computer algebra systems has been proposed.Comment: 12 pages, LaTeX, no figures. Extended version of contribution to AIHENP'95, Pisa, April 3-8, 199

On the Origin of the Enhancementof CP-violating Charge Asymmetries in K→3πK \rightarrow 3\pi Decays Predicted from Chiral Theory

We present an analysis of the enhancement of CP-violating charge asymmetries in $K \rightarrow 3\pi$ decays. Calculations of decay amplitudes are performed on the basis of bosonized strong and weak Lagrangians derived from QCD-motivated quark Lagrangians. We show that the interplay of fourth-order contributions of chiral Lagrangians for strong interactions and penguin operators in weak interactions significantly enhances the charge asymmetries.Comment: DESY 92-106, 15

The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions

© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. Urinary tract infections (UTI) are among the most common infections in humans. Uropathogenic Escherichia coli (UPEC) can invade and replicate within bladder epithelial cells, and some UPEC strains can also survive within macrophages. To understand the UPEC transcriptional programme associated with intramacrophage survival, we performed host-pathogen co-transcriptome analyses using RNA sequencing. Mouse bone marrow-derived macrophages (BMMs) were challenged over a 24h time course with two UPEC reference strains that possess contrasting intramacrophage phenotypes: UTI89, which survives in BMMs, and 83972, which is killed by BMMs. Neither of these strains caused significant BMM cell death at the low multiplicity of infection that was used in this study. We developed an effective computational framework that simultaneously separated, annotated and quantified the mammalian and bacterial transcriptomes. Bone marrow-derived macrophages responded to the two UPEC strains with a broadly similar gene expression programme. In contrast, the transcriptional responses of the UPEC strains diverged markedly from each other. We identified UTI89 genes up-regulated at 24h post-infection, and hypothesized that some may contribute to intramacrophage survival. Indeed, we showed that deletion of one such gene (pspA) significantly reduced UTI89 survival within BMMs. Our study provides a technological framework for simultaneously capturing global changes at the transcriptional level in co-cultures, and has generated new insights into the mechanisms that UPEC use to persist within the intramacrophage environment

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1 beta (IL-1 beta) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin a-hemolysin mediated a substantial proportion of CFT073-triggered IL-1 beta secretion in mousebut nothumanmacrophages. There wasalso a more substantial alpha-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely alpha-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an alpha-hemolysin-independent IL-1 beta secretion pathway in human macrophages. This has important implications for understanding UTI in humans

Progastrin Represses the Alternative Activation of Human Macrophages and Modulates Their Influence on Colon Cancer Epithelial Cells

Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influence of these peptides on the phenotype of macrophages differentiated from human peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was similar in tumoral and normal surrounding tissue, but the number of M2 macrophages (CD206+ cells) was significantly higher in the tumor. However, the number of these tumor-associated M2 macrophages correlated negatively with the immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages differentiated from human peripheral monocytes in the presence of progastrin showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers (CD86, IL12). Progastrin induced similar effects in mature macrophages treated with IL4 to obtain a M2-phenotype or with LPS plus IFNγ to generate M1-macrophages. Macrophages differentiated in the presence of progastrin presented a reduced expression of Wnt ligands and decreased the number and increased cell death of co-cultured colorectal cancer epithelial cells. Our results suggest that progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This effect exerted on tumor associated macrophages may modulate cancer progression and should be taken into account when analyzing the therapeutic value of gastrin immunoneutralization