Analysing Dynamical Behavior of Cellular Networks via Stochastic Bifurcations

The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types

New Hydrazinothiazole Derivatives of Usnic Acid as Potent Tdp1 Inhibitors.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective

Interaction of Copper-Based Nanoparticles to Soil, Terrestrial, and Aquatic Systems: Critical Review of the State of the Science and Future Perspectives

In the past two decades, increased production and usage of metallic nanoparticles (NPs) has inevitably increased their discharge into the different compartments of the environment, which ultimately paved the way for their uptake and accumulation in various trophic levels of the food chain. Due to these issues, several questions have been raised on the usage of NPs in everyday life and has become a matter of public health concern. Among the metallic NPs, Cu-based NPs have gained popularity due to their cost-effectiveness and multifarious promising uses. Several studies in the past represented the phytotoxicity of Cu-based NPs on plants. However, comprehensive knowledge is still lacking. Additionally, the impact of Cu-based NPs on soil organisms such as agriculturally important microbes, fungi, mycorrhiza, nematode, and earthworms are poorly studied. This review article critically analyses the literature data to achieve a more comprehensive knowledge on the toxicological profile of Cu-based NPs and increase our understanding of the effects of Cu-based NPs on aquatic and terrestrial plants as well as on soil microbial communities. The underlying mechanism of biotransformation of Cu-based NPs and the process of their penetration into plants has also been discussed herein. Overall, this review could provide valuable information to design rules and regulations for the safe disposal of Cu-based NPs into a sustainable environment

Gold microelectrode ensembles: cheap, reusable and stable electrodes for the determination of arsenic (V) under aerobic conditions

The determination of total arsenic through As(V) anodic stripping voltammetry (ASV) is, in some cases, preferable over As(III) ASV. The As(V) ASV procedure has no chemical reduction step from As(V) into As(III), which results in decreased analysis time and no contamination from reducting reagents. A simple and reliable procedure of As(V) determination is proposed. Anodic stripping determination of trace As(V) at gold microelectrode ensembles in diluted HCl solution in the presence of dissolved oxygen is shown. The electrode is based on a carbon black (30%)-polyethylene composite. The sensor was prepared by gold electrodeposition on the surface of the composite electrode. The given sensor is cheap, reliable and stable, especially when electrochemical activation is employed. The experimental parameters for the electrochemical determination were optimized, namely 0.005M HCl as the background electrolyte, the deposition potential -2.2V (versus Ag/AgCl in 1M KCl) and 180mVs-1 linear scan rate. Calibration curves were obtained and were linear in [As(V)] over the 1.5-45 μgL-1 range, with a LOD of 0.5 μgL-1. The effect of common interfering species is studied. The electrochemical behaviour of As(III) form is studied in the same experimental conditions. It was found that As(III) is deposited at lower potentials (starting at -0.6 V) and the sensitivity of As(III) detection is higher, but dependant on the presence of dissolved oxygen. The speciation of inorganic forms of arsenic is discussed. © 2013 Taylor and Francis