Patched 1 expression correlates with biochemical relapse in high-risk prostate cancer patients

There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, as the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa. In this study potential associations between Hh pathway protein expression and clinico-pathological factors, including time to biochemical recurrence (BCR), were investigated using a tissue microarray constructed from benign and malignant prostate samples from 75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh signaling activity was found to differ between benign and malignant prostate tissue, with a greater amount of active Hh signaling present in malignant than benign prostate epithelium. High expression of PTCH1 in malignant prostate epithelium was found to be an independent predictor of BCR in high-risk PCa patients. GLI1 may potentially represent a clinically useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling activity in PCa patients may be useful for risk-stratification, and epithelial PTCH1 expression in particular may be a prognostic marker for BCR in high-risk PCa patients

Regulatory Feedback Loop of Two phz Gene Clusters through 5′-Untranslated Regions in Pseudomonas sp. M18

BACKGROUND: Phenazines are important compounds produced by pseudomonads and other bacteria. Two phz gene clusters called phzA1-G1 and phzA2-G2, respectively, were found in the genome of Pseudomonas sp. M18, an effective biocontrol agent, which is highly homologous to the opportunistic human pathogen P. aeruginosa PAO1, however little is known about the correlation between the expressions of two phz gene clusters. METHODOLOGY/PRINCIPAL FINDINGS: Two chromosomal insertion inactivated mutants for the two gene clusters were constructed respectively and the correlation between the expressions of two phz gene clusters was investigated in strain M18. Phenazine-1-carboxylic acid (PCA) molecules produced from phzA2-G2 gene cluster are able to auto-regulate expression itself and activate the expression of phzA1-G1 gene cluster in a circulated amplification pattern. However, the post-transcriptional expression of phzA1-G1 transcript was blocked principally through 5'-untranslated region (UTR). In contrast, the phzA2-G2 gene cluster was transcribed to a lesser extent and translated efficiently and was negatively regulated by the GacA signal transduction pathway, mainly at a post-transcriptional level. CONCLUSIONS/SIGNIFICANCE: A single molecule, PCA, produced in different quantities by the two phz gene clusters acted as the functional mediator and the two phz gene clusters developed a specific regulatory mechanism which acts through 5'-UTR to transfer a single, but complex bacterial signaling event in Pseudomonas sp. strain M18

Rhamnolipids: diversity of structures, microbial origins and roles

Rhamnolipids are glycolipidic biosurfactants produced by various bacterial species. They were initially found as exoproducts of the opportunistic pathogen Pseudomonas aeruginosa and described as a mixture of four congeners: α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-Rha-C10-C10), α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoate (Rha-Rha-C10), as well as their mono-rhamnolipid congeners Rha-C10-C10 and Rha-C10. The development of more sensitive analytical techniques has lead to the further discovery of a wide diversity of rhamnolipid congeners and homologues (about 60) that are produced at different concentrations by various Pseudomonas species and by bacteria belonging to other families, classes, or even phyla. For example, various Burkholderia species have been shown to produce rhamnolipids that have longer alkyl chains than those produced by P. aeruginosa. In P. aeruginosa, three genes, carried on two distinct operons, code for the enzymes responsible for the final steps of rhamnolipid synthesis: one operon carries the rhlAB genes and the other rhlC. Genes highly similar to rhlA, rhlB, and rhlC have also been found in various Burkholderia species but grouped within one putative operon, and they have been shown to be required for rhamnolipid production as well. The exact physiological function of these secondary metabolites is still unclear. Most identified activities are derived from the surface activity, wetting ability, detergency, and other amphipathic-related properties of these molecules. Indeed, rhamnolipids promote the uptake and biodegradation of poorly soluble substrates, act as immune modulators and virulence factors, have antimicrobial activities, and are involved in surface motility and in bacterial biofilm development

Peat-based organic growbags as a solution to the mineral wool waste problem

The vast amount of solid waste produced each year is one of the greatest problems associated with greenhouse horticulture in some European countries. In particular, the disposal of used growing media arising from the soil-less cultivation of vegetables in mineral wool creates serious difficulties. The non-biodegradability of these mainly inorganic substrates causes environmental concern and has prompted the search for alternative growing media such as cocos derivatives, perlite and resin foam (Fytocell®). Organic substrates in combination with biodegradable material such as plastic, rope and clippings have the advantage that re-use or recycling of the waste is easier, cheaper and more environmentally friendly than for mineral wool. However, the differing physical and chemical characteristics of the alternative substrates may affect yield significantly. Substrates based respectively on peat and peat with cocos derivatives were tested against a mineral wool control for the production of tomato in three consecutive years. Both organic substrates were placed in biodegradable plastic bags. Greenhouse experiments demonstrated that plants grown in the pure peat substrate rooted more easily than plants grown in the peat-cocos substrate or mineral wool, and that they developed less blossom-end rot in both peat substrates than in mineral wool. Due to the buffering capacity of the organic substrates, the electrical conductivity of the draining water appeared to be more stable during cultivation. The total yield of tomato fruits was similar for all substrates, and no differences between substrates could be observed in the quality of the fruits produced. On the other hand, flavour tests demonstrated that plants grown on peat substrate produced more tasty fruits under certain conditions. The results of this study show that organic growbags are promising and competitive alternatives to mineral wool