Cytotoxic and antimitotic effects of N-containing Monascus metabolites studied using immortalized human kidney epithelial cells

Recently the first Monascus metabolites with a pyridine ring were detected, the monascopyridines A and B. They are formally dehydrogenated derivatives of the red rice pigments rubropunctamine and monascorubramine. Because of their structural similarity, the toxicological effects of these secondary metabolites were studied using immortalized human kidney epithelial cells. The cytotoxicity was determined with the following different endpoint detection methods: metabolic activity, trypan blue exclusion, and electronic cell counting. The compounds led to EC(50) values between 11 and 31 micromol/L but the pigments caused a stronger reduction of the cell viability. Also, the apoptotic potential was examined by measuring caspase 3 activity and detecting apoptotic bodies, but none of the tested compounds induced apoptosis. All four substances caused a rise of the mitotic index to about 9% (100 micromol/L monascopyridine A and B) and 20% (25 micromol/L rubropunctamine and monascorubramine). The significant decrease of the ratio of cells in the ana- and telophase to cells in the prometa- and metaphase proved a stop of the mitosis at the meta- to anaphase control point. The compounds caused mitotic arrest and the formation of structural damages like c-mitosis through interaction with the mitotic spindle. These effects point to an aneuploidy inducing potential, which is linked to cancer formation.     

New Monascus metabolites: structure elucidation and toxicological properties studied with immortalized human kidney epithelial cells

Monascus sp. are used for the production of red yeast rice, which has been applied in Asian food and medicine for centuries. The fungi form several secondary metabolites, among others the monascopyridines A and B. We have now detected two new monascopyridines (named C and D) with similar UV absorption spectra and maxima at 306-307 nm in red rice fermented with M. purpureus. The new monascopyridines have the same chromophores as the already known and differ in a missing gamma-lactone ring only. Monascopyridine C has a hexanoyl side chain, whereas monascopyridine D is the higher homologue with an octanoyl side chain. The toxicological properties of monascopyridines were studied using immortalized human kidney epithelial cells, displaying cytotoxic effects in micromolar concentrations with median effective concentration values between 20.7 and 43.2 micromol/L, depending on the compound and method used. The monascopyridines C and D did not induce apoptosis. However, they caused a rise of the mitotic index from 3.21 +/- 0.27% (control) to maximum 8.14 +/- 0.89% (monascopyridine D) by an accumulation of cells in the metaphase with a simultaneous decrease of cells in the ana- and telophase. Monascopyridine-induced metaphase arrest is caused by a partial or complete loss of the spindle apparatus as indicated by the occurrence of abnormal metaphases and immunological staining of alpha-tubulin. These effects are indicating an aneuploidic potential and therefore the monascopyridines C and D might contribute to tumor formations.     

Iceberg lettuce as suggested source of a nationwide outbreak caused by two Salmonella serotypes, Newport and Reading, in Finland in 2008

A nationwide outbreak of Salmonella enterica serotypes Newport and Reading occurred between 17 October and 28 November 2008 in Finland. A total of 77 culture-confirmed Salmonella Newport and 30 Salmonella Reading cases, including one case with a double infection, were reported. All strains isolated from the patients were subtyped using serotyping, microbial resistance profiling, and pulsed-field gel electrophoresis (PFGE). Here, the PFGE patterns of the studied Salmonella Newport strains were identical, whereas four different PFGE profiles were found among the Salmonella Reading strains. Two elderly patients died within 2 weeks of the onset of symptoms. Three geographical clusters of cases with an epidemiological link were identified. The traceback investigation suggested that the factor connecting the cases was ready-chopped iceberg lettuce available for mass catering use. However, none of the tested food, environmental samples, or the samples taken from the staff of the processing plant contained Salmonella bacteria. Tracing back to outbreak sources with a short shelf life can be complex.     

Implementation of Machine Learning for Autonomic Capabilities in Self-Organizing Heterogeneous Networks

The 3GPP’s self-organizing networks (SONs) standards are a huge step towards the autonomic networking concept. They are the response to the increasing complexity and size of the mobile networks. This paper proposes a novel scheme for SONs. This scheme is based on machine learning techniques and additionally adopting the concept of abstraction and modularity. The implementation of these concepts in a machine learning scheme allows the usage of independent vendor and technology algorithms and reusability of the proposed approach for different optimization tasks in a network. The scheme is tested for solving an energy saving optimization problem in a heterogeneous network. The results from simulation experiments show that such an approach could be an appropriate solution for developing a full self-managing future network.     

Modellierung des Single Burning Item Tests

Modelling the Single Burning Item Test Harmonisation in Europe led to new standards, tests and classification of building products in fire safety. The Single Burning Item (SBI) test is the new reaction to fire test for the intermediate level. In the test a developing fire caused by a single burning item, e.g. a burning waste paper basket, is simulated. Numerical investigations of the SBI test have been performed by the Federal Institute for Materials Research and Testing (BAM) in cooperation with Technical University Berlin. Two CFD (Computational Fluid Dynamics) codes, Fluent and FDS, have been used to develop models of the SBI test. Data of our own experiments and literature has been used to validate the numerical models. Variation of ventilation in the burning room and variation of ambient air temperature lead to significant changes in temperatures and flow velocities in the burning room. The SBI standard EN 13823 allows the ventilation and ambient air temperature to be in a range. New experiments are necessary to show the effect of one single parameter like ambient air temperature. But the used data and the numerical results give reason to think about narrowing the ranges for ventilation and ambient air temperature in the standard.     

Terminal and transient drop rise velocity of single toluene droplets in water

The knowledge of the drop rise velocity in dispersed systems is of fundamental importance. Especially, the residence time is needed for calculation of mass transfer rates in extraction columns. This work deals with fluid dynamic measurements of toluene droplets rising in water ranging from 1.0 to 7.0 mm, with the premise of high purity of the used chemicals. The toluene/water‐system is widely used as a test system with high interfacial tension. A semiempirical correlation for pure systems to predict the terminal velocity of single rising/falling droplets based on experimental data is presented. Results show that a distinction between maximum and characteristic mean values of the drop rise velocity is necessary, especially in the diameter range 2.4–3.0 mm where unexpected velocity fluctuations occur. Two distinct terminal rise velocities were observed for 3 mm droplets. Furthermore, comparisons of the Weber‐Reynolds‐correlation and the drag coefficient with correlations from literature show good agreement. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

Predicting and tuning physicochemical properties in lead optimization: amine basicities

This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based organocatalysis.