Molecular Recognition of Metal Complexes by DNA: A Comparative Study of the Interactions of the Parent Complexes [PtCl(TERPY)]Cl and [AuCl(TERPY)]Cl (2) with Double Stranded DNA

The interactions of the parent complexes [AuCl(Terpy)]Cl2 and [PtCl(Terpy)]Cl with DNA were analysed by various physicochemical methods. Surprisingly, these metal complexes produce different interaction patterns with DNA in spite of their profound structural similarity. Indeed, important modifications are detected in the characteristic UV-Vis bands of [PtCl(Terpy)]Cl upon addition of ct-DNA, while the spectrum of [AuCl(Terpy)]Cl2 is almost unaffected. Gel electrophoresis studies confirm these findings: [PtCl(Terpy)]Cl — but not [AuCl(Terpy)]Cl2 — retards significantly the mobility of the supercoiled form of the pHV14 plasmid after a short incubation time. Ultrafiltration studies indicate that the affinity of [PtCl(Terpy)]Cl for ct-DNA is significantly greater than that of [AuCl(Terpy)]Cl2. On the other hand, both [AuCl(Terpy)]Cl2 and [PtCl(Terpy)]Cl induce important changes in the CD spectrum of ct-DNA, at high concentration, and increase its Tm value. Remarkably, the analysed metal-complex/DNA interaction patterns depend critically on the incubation times. We propose that [PtCl(Terpy)]Cl quickly intercalates DNA; then, formation of coordinative bonds progressively takes place with time. At variance, [AuCl(Terpy)]Cl2 first interacts electrostatically with the DNA surface, with subsequent slow formation of some coordinative bonds

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

Investigation of Coolant Mixing in Reactor VVER-1000

We present an experimental investigation of coolant mixing in downcomer and lower plenum of VVER-1000 here. The arrangement of the problem, the methodology and results are discussed. Three groups of experiments simulating coolant mixing were executed: in conditions of RCP start-up, during natural circulation recovery in the course of SB LOCA and in conditions of stable operation of different amount of RCPs. Results of experiments are used for validation of numerical codes

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

Multilevel Selection in Models of Prebiotic Evolution II: A Direct Comparison of Compartmentalization and Spatial Self-Organization

Multilevel selection has been indicated as an essential factor for the evolution of complexity in interacting RNA-like replicator systems. There are two types of multilevel selection mechanisms: implicit and explicit. For implicit multilevel selection, spatial self-organization of replicator populations has been suggested, which leads to higher level selection among emergent mesoscopic spatial patterns (traveling waves). For explicit multilevel selection, compartmentalization of replicators by vesicles has been suggested, which leads to higher level evolutionary dynamics among explicitly imposed mesoscopic entities (protocells). Historically, these mechanisms have been given separate consideration for the interests on its own. Here, we make a direct comparison between spatial self-organization and compartmentalization in simulated RNA-like replicator systems. Firstly, we show that both mechanisms achieve the macroscopic stability of a replicator system through the evolutionary dynamics on mesoscopic entities that counteract that of microscopic entities. Secondly, we show that a striking difference exists between the two mechanisms regarding their possible influence on the long-term evolutionary dynamics, which happens under an emergent trade-off situation arising from the multilevel selection. The difference is explained in terms of the difference in the stability between self-organized mesoscopic entities and externally imposed mesoscopic entities. Thirdly, we show that a sharp transition happens in the long-term evolutionary dynamics of the compartmentalized system as a function of replicator mutation rate. Fourthly, the results imply that spatial self-organization can allow the evolution of stable folding in parasitic replicators without any specific functionality in the folding itself. Finally, the results are discussed in relation to the experimental synthesis of chemical Darwinian systems and to the multilevel selection theory of evolutionary biology in general. To conclude, novel evolutionary directions can emerge through interactions between the evolutionary dynamics on multiple levels of organization. Different multilevel selection mechanisms can produce a difference in the long-term evolutionary trend of identical microscopic entities

Endophytic fungi from the roots of horseradish (Armoracia rusticana) and their interactions with the defensive metabolites of the glucosinolate myrosinase – isothiocyanate system

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