Living in Sofia is associated with a risk for antibiotic resistance in Helicobacter pylori: a Bulgarian study

The aim of the retrospective study was to evaluate geographic regions and residence places as possible risk factors for primary Helicobacter pylori antibiotic resistance in Bulgaria. Data from Sofia region, exhibiting the highest living density, were compared to those from other residence places. In total, 588 H. pylori strains from untreated adults who filled a questionnaire were evaluated. Strain susceptibility was assessed by a breakpoint susceptibility test. Resistance rates to metronidazole and clarithromycin have been found to increase, and that to tetracycline has been found to decrease over years. Clarithromycin resistance was 1.7-fold higher in Sofia inhabitants (23.5 %) than elsewhere (13.8 %) and 4.7-fold higher than that in villages (5.0 %). Moreover, the clarithromycin resistance rate was 2.6-fold lower in northern region (8.2 %) than in southern region (21.7 %). On multivariate analysis, sex and residence place were independent predictors for metronidazole resistance. Men were at lower risk for metronidazole resistance compared with women [odds ratio (OR) 0.703; 95 % confidence interval (CI) 0.499–0.990]. Importantly, Sofia inhabitants were at higher risk for the resistance compared with those living elsewhere (OR 1.453; 95 % CI 1.009–2.093). In conclusion, living in Sofia was associated with a risk for antibiotic resistance in H. pylori-positive adults. Living density could be associated with H. pylori resistance rates.     

Rosmarinic acid production by Lavandula vera MM cell-suspension culture

The time courses of growth and rosmarinic acid production by Lavandula vera MM cell suspension were investigated. The uptake of the main nutrients (sucrose, nitrogen, phosphorus, K, Ca, Mg) was followed during cultivation and the data on the physiology of the L. vera MM cell culture are presented. It was established that the cell culture synthesizes rosmarinic acid during the linear phase of growth for a relatively short period (between the 4th and 8th days of cultivation). The influence of sucrose concentration in the nutrient medium on cell growth and accumulation of rosmarinic acid by L. vera MM cell culture was investigated. The results showed that 7% sucrose in the nutrient medium ensured a steady growth of the cell suspension and increased the yield of rosmarinic acid (29.2 g/l dry biomass and 507.5 mg/l rosmarinic acid compared to 13.0 g/l dry biomass and 68.6 mg/l rosmarinic acid for the control cultivation with 3% sucrose). Received: 17 September 1996 / Received revision: 31 January 1997 / Accepted: 1 February 1997     

Small Molecule Antagonists of the Wnt/Beta-Catenin Signaling Pathway Target Breast Tumor-Initiating Cells in a Her2/Neu Mouse Model of Breast Cancer

Background

Recent evidence suggests that human breast cancer is sustained by a minor subpopulation of breast tumor-initiating cells (BTIC), which confer resistance to anticancer therapies and consequently must be eradicated to achieve durable breast cancer cure.

Methods/Findings

To identify signaling pathways that might be targeted to eliminate BTIC, while sparing their normal stem and progenitor cell counterparts, we performed global gene expression profiling of BTIC- and mammary epithelial stem/progenitor cell- enriched cultures derived from mouse mammary tumors and mammary glands, respectively. Such analyses suggested a role for the Wnt/Beta-catenin signaling pathway in maintaining the viability and or sustaining the self-renewal of BTICs in vitro. To determine whether the Wnt/Beta-catenin pathway played a role in BTIC processes we employed a chemical genomics approach. We found that pharmacological inhibitors of Wnt/β-catenin signaling inhibited sphere- and colony-formation by primary breast tumor cells and primary mammary epithelial cells, as well as by tumorsphere- and mammosphere-derived cells. Serial assays of self-renewal in vitro revealed that the Wnt/Beta-catenin signaling inhibitor PKF118–310 irreversibly affected BTIC, whereas it functioned reversibly to suspend the self-renewal of mammary epithelial stem/progenitor cells. Incubation of primary tumor cells in vitro with PKF118–310 eliminated their capacity to subsequently seed tumor growth after transplant into syngeneic mice. Administration of PKF118–310 to tumor-bearing mice halted tumor growth in vivo. Moreover, viable tumor cells harvested from PKF118–310 treated mice were unable to seed the growth of secondary tumors after transplant.

Conclusions

These studies demonstrate that inhibitors of Wnt/β-catenin signaling eradicated BTIC in vitro and in vivo and provide a compelling rationale for developing such antagonists for breast cancer therapy.     

A Suite of Models to Support the Quantitative Assessment of Spread in Pest Risk Analysis

Pest Risk Analyses (PRAs) are conducted worldwide to decide whether and how exotic plant pests should be regulated to prevent invasion. There is an increasing demand for science-based risk mapping in PRA. Spread plays a key role in determining the potential distribution of pests, but there is no suitable spread modelling tool available for pest risk analysts. Existing models are species specific, biologically and technically complex, and data hungry. Here we present a set of four simple and generic spread models that can be parameterised with limited data. Simulations with these models generate maps of the potential expansion of an invasive species at continental scale. The models have one to three biological parameters. They differ in whether they treat spatial processes implicitly or explicitly, and in whether they consider pest density or pest presence/absence only. The four models represent four complementary perspectives on the process of invasion and, because they have different initial conditions, they can be considered as alternative scenarios. All models take into account habitat distribution and climate. We present an application of each of the four models to the western corn rootworm, Diabrotica virgifera virgifera, using historic data on its spread in Europe. Further tests as proof of concept were conducted with a broad range of taxa (insects, nematodes, plants, and plant pathogens). Pest risk analysts, the intended model users, found the model outputs to be generally credible and useful. The estimation of parameters from data requires insights into population dynamics theory, and this requires guidance. If used appropriately, these generic spread models provide a transparent and objective tool for evaluating the potential spread of pests in PRAs. Further work is needed to validate models, build familiarity in the user community and create a database of species parameters to help realize their potential in PRA practice.     

Copper removal from aqueous solution using Aspergillus niger mycelia in free and polyurethane-bound form

This study assesses the ability of mycelia of Aspergillus niger B-77 (both free and immobilized on polyurethane foam) to remove copper from single-ion solution. All experiments were conducted using 0.5 mM solutions of CuSO4.5H2O. Mycelia immobilized on polyurethane foam cells showed a three-fold increase in uptake, compared with that of free cells. The efficiency of copper removal (mg Cu2+ removed/mg Cu2+ added) in a column system reached more than 99% before the break-through point was attained.     

Ultracytochemical localization of ATP-hydrolysing activity in vegetative cells, spores and isolated cytoplasmic membranes of Bacillus subtilis 168

The localization of ATP-hydrolysing activity in vegetative cells, spores and isolated membranes of Bacillus subtilis 168 was studied by a cytochemical method combined with electron microscopy. The activity was located mainly in the cytoplasmic membrane and the mesosomes, and was also found in the inner layer of the cell wall facing the cytoplasmic membrane. Activity was also detected in the cross-membranes of dividing cells and in spore coats. The product of the reaction was observed either as fine electron-dense granules incorporated into the membranes, or as high-contrast lead precipitates on the surfaces of the membranes.     

Preliminary study on biomarkers for the fungal resistance in Vitis vinifera leaves

We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites – - and γ-tocopherol, squalene, -amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis.     

Release of rosmarinic acid by Lavandula vera MM cell suspension in two-phase culture systems

Studies were conducted on the cultivation of Lavandula vera MM cell suspensions in different culture systems for the release of extracellular rosmarinic acid (RA). It was established that during cultivation with Amberlite XAD-4 as a second phase, 6.4% of the total content of RA was adsorbed. When L. vera MM cell suspension was cultivated in an aqueous two-phase system formed by adding 4% polyethylene glycol (MW 20,000) and 7.5% dextran (MW 70,000), 11.8% of the total RA content was released into the top polyethylene glycol phase.     

The influence of phenylalanine on accumulation of rosmarinic and caffeic acids by Lavandula vera MM cell culture

Lavandula vera MM cell suspension culture was grown in Linsmayer-Skoog medium with different concentrations of phenylalanine. Adding phenylalanine to the medium (0.1–0.5 g/l) enhanced accumulation of caffeic acid in parallel with rosmarinic acid. When 0.3 g phenylalanine/l was added, the yield of rosmarinic and caffeic acids reached 87 mg/l and 60 mg/l respectively, compared with 68 mg/l and 4 mg/l in controls (without phenylalanine).