DNA interaction studies of tridentate bridged Ru(II)-Pt(II) mixed-metal supramolecules

Reported herein are studies of the concentration and temperature dependent interactions with DNA of the stereochemically defined mixed-metal supramolecular complexes, [(tpy)Ru(tppz)PtCl](PF₆)₃ and [ClPt(tppz)Ru(tppz)PtCl](PF₆)₄ (tpy = 2,2′:6′,2′′-terpyridine and tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine). These metal complexes couple a ruthenium based light absorber (LA) to the bioactive platinum sites (BAS) using a tridentate bridging ligand (BL). The complexes exhibit intense Ru → tppz(π∗) metal to ligand charge transfer (MLCT) transitions in the visible region and adopt a square planar geometry around the Pt(II) center. The effect of incubating these metal complexes with DNA on the subsequent migration of DNA through an agarose gel was found to be more dramatic than that observed for the well known anticancer drug, cis-[Pt(NH₃)₂Cl₂] (cisplatin). This effect was enhanced with increased incubation temperature. Unwinding of supercoiled plasmid DNA was found to be more pronounced for the trimetallic complex, [ClPt(tppz)Ru(tppz)PtCl](PF₆)₄, than for the bimetallic complex, [(tpy)Ru(tppz)PtCl](PF₆)₃.     

Interaction of cytochrome c with lipid monolayers

Cytochrome c was permitted to react with several lipid monolayers in which surface pressure, lipid charge and unsaturation were varied. Cytochrome c interaction with the films caused increased surface pressures, and the magnitude and rate of surface pressure change were compared under a variety of experimental conditions. Large surface pressure changes were associated with more expanded films, whereas greater rates of surface pressure change were associated with favorable charge interaction between cytochrome c and the films. Under the most favorable conditions, rates of surface pressure change were limited principally by protein diffusion to the interface. From these data, it is suggested that unsaturation in lipids of biological membranes may help stabilise non-polar protein-lipid interactions, whereas charge interaction may facilitate and direct initial binding of protein to membranes.     

Intensity of Mutualism Breakdown Is Determined by Temperature Not Amplification of Wolbachia Genes

Wolbachia are maternally transmitted intracellular bacterial symbionts that infect approximately 40% of all insect species. Though several strains of Wolbachia naturally infect Drosophila melanogaster and provide resistance against viral pathogens, or provision metabolites during periods of nutritional stress, one virulent strain, wMelPop, reduces fly lifespan by half, possibly as a consequence of over-replication. While the mechanisms that allow wMelPop to over-replicate are still of debate, a unique tandem repeat locus in the wMelPop genome that contains eight genes, referred to as the “Octomom” locus has been identified and is thought to play an important regulatory role. Estimates of Octomom locus copy number correlated increasing copy number to both Wolbachia bacterial density and increased pathology. Here we demonstrate that infected fly pathology is not dependent on an increased Octomom copy number, but does strongly correlate with increasing temperature. When measured across developmental time, we also show Octomom copy number to be highly variable across developmental time within a single generation. Using a second pathogenic strain of Wolbachia, we further demonstrate reduced insect lifespan can occur independently of a high Octomom locus copy number. Taken together, this data demonstrates that the mechanism/s of wMelPop virulence is more complex than has been previously described.     

Cell kinetics of a rat thyroid transplantable tumour

Changes in morphology and cell kinetics are described in a rat thyroid transplantable tumour (TTT) during the first few transplant generations. The growth of TTT in animals was possible only with an increased circulation level of the thyroid stimulating hormone (TSH). With serial transplantation subcutaneously in isologous animals, the morphology of TTT changed dramatically from that of a follicular tumour in the 3rd passage to become, by the 9th generation, a poorly differentiated tumour with a trabecular arrangement of cells. This change in tumour morphology was accompanied by an increase in the number of proliferating cells--mitotic index (MI), [3H]thymidine labelling index (LI), growth fraction (GF)--and cell loss factor (O) as well as a decrease in the cell cycle time (Tc) and potential population doubling time (TPD). TTT belongs to the class of tumours with a low proliferative activity and might be used in a variety of cell kinetic, radiobiological and chemotherapy studies.     

SOME SOURCES OF BIAS IN CONSUMER TESTING

Data sets from three studies were examined to determine the effects of brand identification and package design on consumer responses during product evaluation. In these studies, consumers evaluated products with or without brand identification, compared products in standardized conditions, and compared products in different package designs with different or identical product contents. Measurement of consumer responses for all studies was based on 9-point hedonic scale. The results of the study showed that consumers were less critical in their evaluation when the samples being assessed were identified by brand names. Brand identification and package design, when not concealed in the comparison of product contents, resulted in consumer response bias. Also, the popularity of a brand influenced consumer's perception of products.     

A Kinetic Model of the Inositol Trisphosphate Receptor Based on Single-Channel Data

In many cell types, the inositol trisphosphate receptor is one of the important components controlling intracellular calcium dynamics, and an understanding of this receptor is necessary for an understanding of calcium oscillations and waves. Based on single-channel data from the type-I inositol trisphosphate receptor, and using a Markov chain Monte Carlo approach, we show that the most complex time-dependent model that can be unambiguously determined from steady-state data is one with three closed states and one open state, and we determine how the rate constants depend on calcium. Because the transitions between these states are complex functions of calcium concentration, each model state must correspond to a group of physical states. We fit two different topologies and find that both models predict that the main effect of [Ca²⁺] is to modulate the probability that the receptor is in a state that is able to open, rather than to modulate the transition rate to the open state.