Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.

Certain Escherichia coli (E. coli) strains are attaching and effacing (A/E) lesion pathogens that primarily infect intestinal epithelial cells. They cause actin restructuring and polymerization within the host cell to create an actin-rich protrusion below the site of adherence, termed the pedestal. Although there is clarity on the pathways initiating pedestal formation, the underlying purpose(s) of the pedestal remains ambiguous. The conservation of pedestal-forming activity across multiple pathogens and redundancy in formation pathways indicate a pathogenic advantage. However, few decisive conclusions have been drawn, given that the results vary between model systems. Some research argues that the pedestal increases the colonization capability of the bacterium. These studies utilize A/E pathogens specifically deficient in pedestal formation to evaluate adhesion and intestinal colonization following infection. There have been many proposed mechanisms for the colonization benefit conferred by the pedestal. One suggested benefit is that the pedestal allows for direct cytosolic anchoring through incorporation of the established host cortical actin, causing a stable link between the pathogen and cell structure. The pedestal may confer enhanced motility, as enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are better able to migrate on the surface of host cells and infect neighboring cells in the presence of the pedestal. Additionally, some research suggests that the pedestal improves effector delivery. This review will investigate the purpose of pedestal formation using evidence from recent literature and will critically evaluate the methodology and model systems. Most importantly, we will contextualize the proposed functions to reconcile potential synergistic effects.

The galanin system in cancer.

Many tumours of neuroendocrine origin, and also an increasing number of non-neuroendocrine cancers, have been shown to express neuropeptides and/or their corresponding receptors. These peptides and receptors represent the molecular basis for in vivo diagnostic or therapeutic targeting of cancer with radiolabelled or cytotoxic peptide analogues. Galanin is a classical neuropeptide that functions in diverse physiological processes such as food intake, nociception, and blood pressure regulation, and it can also act as a growth factor for neurons. Expression of galanin peptide has been detected in pheochromocytoma, pituitary adenoma, neuroblastic tumours, gastrointestinal cancer, squamous cell carcinoma, brain tumours, melanoma, breast cancer and embryonal carcinoma. In several cancers and tumour cell lines expression of galanin receptors--three are known (GalR1, 2 and 3)--has been shown as well. Expression of peptide or receptors has been correlated with tumour stage or subtypes of pituitary adenoma, neuroblastic tumours, colon carcinoma and squamous cell carcinoma. Galanin treatment has tumour-reducing effects in murine models of gastrointestinal cancer, whereas in animal experiments on adenoma formation, galanin seems to act as a growth factor, promoting both proliferation and tumour formation. In cell culture experiments on tumour cell lines, galanin has shown growth promoting or inhibiting effects. Activation of GalR1 is generally anti-proliferative, whereas activation of GalR2 can have pro- or anti-proliferative effects. Therefore, galanin and its receptors are promising targets for diagnosis and treatment of several types of tumours.

MMP-9 haplotypes and carotid artery atherosclerosis: an association study introducing a novel multicolour multiplex RealTime PCR protocol.

BACKGROUND: Among other matrix metalloproteinases (MMPs), gelatinase B (MMP-9) is discussed to be associated with the pathogenesis of vascular diseases. Two single nucleotide polymorphisms (SNPs) of the MMP-9 gene, C-1562T in the promoter region and a G/A transition in exon 6 (R + 279Q), have been addressed in previous association studies which, however, produced conflicting results. MATERIAL AND METHODS: A novel multiplex RealTime PCR protocol for the fast and simultaneous detection of both polymorphisms is presented, which was used for genotyping 1737 participants of a prospective study investigating genetic factors influencing the progression of atherosclerosis. RESULTS: Haplotype analysis revealed -1562C/+279Q as the major haplotype in this population. Allelic distribution of the C-1562T polymorphism was consistent with data published for similar cohorts; however, we found that R + 279Q allelic distribution appears to vary significantly among Caucasian populations. Considering clinical data available from 1487 participants, we found significant associations between the presence of atherosclerotic plaque and the CA-haplotype in men (P = 0.028, phi = 0.08), and between the AG variant of exon 6 and common carotid artery intima-media thickness (CIMT) in women (P = 0.004, Eta(2) = 0.019). CONCLUSIONS: In summary, our results demonstrate associations of MMP-9 genotypes with different stages of carotid atherosclerosis.