Interaction of delta sleep-inducing peptide and its analogues with cellular membranes: A structure-function analysis

The possibility of a correlation between the membrane properties of the delta sleep-inducing peptide (DSIP) and its analogues and their biological activity in vivo was examined by a comparative study of the membrane effects of these peptides. The peptides exhibiting biological activity in vivo were shown to cause a statistically reliable disordering of lipids in thrombocyte plasma membranes similar to the effect of DSIP. The membrane effect of the D-Val²-, D-Tyr²-, and Tyr¹, Pro² analogues of DSIP had the same bimodal dose dependence characteristic of natural DSIP. Only a slight nonspecific lipid disordering was registered for Trp-Asp-Ala-Ser-Gly-Glu, a biologically inactive hexapeptide analogue. These results indicate a correlation between the biological activity of the peptides during in vivo tests and their membrane properties in vitro. The structure-function relationship was studied within the group of DSIP analogues examined in vitro. The DSIP modeling effect, especially pronounced under the action of stress factors, was suggested to be directly associated with the ability of DSIP to change the dynamic structure of biological membranes.     

Compaction of single supercoiled DNA molecules adsorbed onto amino mica

A model of possible conformational transitions of supercoiled DNA in vitro in the absence of proteins under the conditions of increasing degree of compaction was developed. A 3993-bp pGEMEX supercoiled DNA immobilized on various substrates (freshly cleaved mica, standard amino mica, and modified amino mica with a hydrophobicity higher than that of standard amino mica) was visualized by atomic force microscopy in air. On the modified amino mica, which has an increased density of surface positive charges, single molecules with an extremely high degree of compaction were visualized in addition to plectonemic DNA molecules. As the degree of DNA supercoiling increased, the length of the first-order superhelical axis of molecules decreased from 570 to 370 nm, followed by the formation of second-and third-order superhelical axes about 280 and 140 nm long, respectively. The compaction of molecules ends with the formation of minitoroids about 50 nm in diameter and molecules of spherical shape. It was shown that the compaction of single supercoiled DNA molecules immobilized on amino mica to the level of minitoroids and spheroids is due to the shielding of mutually repulsing negatively charged phosphate groups of DNA by positively charged amino groups of the amino mica, which has a high charge density of its surface.     

A synthesis of cinnamoyloxyisoflavones

Interaction of 7-hydroxyisoflavonones with cinnamoyl chloride results in cinnamoyloxyisoflavonones.     

Similarities,Differences and Synergisms Between HERA and LCA—An Analysis at Three Levels

Linkages between Human and Environmental Risk Assessment (HERA) and Life-Cycle Assessment (LCA) can be analyzed at three levels: the basic equations to describe environmental behavior and dose-response relationships of chemicals; the overall model structure of these tools; and the applications of the tools. At level 1 few differences exist: both tools use essentially the same fate and effect models, including their coefficients and data. At level 2 distinctive differences emerge: regional or life-cycle perspective, emission pulses or fluxes, scope of chemicals and types of impacts, use of characterization factors, spatial and temporal detail, aggregation of effects, and the functional unit as basis of the assessment. Although the two tools typically differ in all these aspects, only the functional unit issue renders the tools fundamentally different, expressing itself also in some main characteristics of the modeling structure. This impedes full integration, which is underpinned in mathematical terms. At level 3 the aims of the tools are complementary: quantified risk estimates of chemicals for HERA versus quantified product assessment for LCA. Here, beneficial synergism is possible between the two tools, as illustrated by some cases. These also illustrate that where full integration is suggested, in practice this is not achieved, thus in fact supporting the conclusions.     

Methods for Identifying a Default Cross-Species Scaling Factor

The need to identify “toxicologically equivalent” doses across different species is a major issue in toxicology and risk assessment. In this article, we describe an approach for establishing default cross-species extrapolation factors used to scale oral doses across species for non-carcinogenic endpoints. This work represents part of an on-going effort to harmonize the way animal data are evaluated for carcinogenic and non-carcinogenic endpoints. In addition to considering default scaling factors, we also discuss how chemical-specific data (e.g., metabolic or mechanistic data) can be incorporated into the dose extrapolation process. After first examining the required properties of a default scaling methodology, we consider scaling approaches based on empirical relationships observed for particular classes of compounds and also more theoretical approaches based on general physiological principles (i.e, allometry). The available data suggest that the empirical and allometric approaches each provide support for the idea that toxicological risks are approximately equal when daily oral doses are proportional to body weight raised to the 3/4-power. We also discuss specific challenges for dose scaling related to different routes of exposure, acute versus chronic toxicity, and extrapolations related to particular life stages (e.g., childhood).     

Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities, serum trace elements (Se, Cu, Zn) and cardiovascular risk factors in subjects from the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago, Portugal

Activities of whole blood glutathione peroxidase (GSH-Px) and erythrocyte superoxide dismutase (SOD) and serum levels of selenium (Se), copper (Cu) and zinc (Zn) were measured in 118 apparently healthy subjects aged 20-60 years from the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago, Portugal. Data were analysed by age/gender, lipid profile and blood pressure as cardiovascular risk factors searching for their relevance when assessing reference values for antioxidant biomarkers. GSH-Px was in the same range, but SOD was significantly lower than in other Portuguese populations. Neither activity differed with gender. GSH-Px activity increased with age, namely in normolipidemic men versus the hyperlipidemic group in which a decrease was observed. This suggests a progressive impairment of GSH-Px with age caused by an enhanced production of oxidant species in hyperlipidemia. GSH-Px was 30% lower in male hypertensives versus normotensives. SOD activity did not relate to age or blood pressure but was 17% higher in the hyperlipidemic men versus the normolipidemic group, suggesting a better antioxidant protection by SOD than by GSH-Px in hyperlipidemia and hypertension. Se was higher in men versus women, particularly in the older subjects, and partly related to hyperlipidemia. Zn levels showed a similar dependency on gender, not related to age or lipid profile. Cu levels were much higher in women than in men in all age or lipid profile classes and decreased in hyperlipidemia. They were lowered with age in both genders, particularly in normolipidemic women. The present research therefore suggests that hyperlipidemia and hypertension do affect antioxidant status and should be considered when assessing antioxidant biomarkers in blood.     

A Brownian ratchet for protein translocation including dissociation of ratcheting sites

We study a model for the translocation of proteins across membranes through a nanopore using a ratcheting mechanism. When the protein enters the nanopore it diffuses in and out of the pore according to a Brownian motion. Moreover, it is bound by ratcheting molecules which hinder the diffusion of the protein out of the nanopore, i.e. the Brownian motion is reflected such that no ratcheting molecule exits the pore. New ratcheting molecules bind at rate γ. Extending our previous approach (Depperschmidt and Pfaffelhuber in Stoch Processes Appl 120:901–925, 2010) we allow the ratcheting molecules to dissociate (at rate δ) from the protein (Model I). We also provide an approximate model (Model II) which assumes a Poisson equilibrium of ratcheting molecules on one side of the current reflection boundary. Using analytical methods and simulations we show that the speeds of both models are approximately the same. Our analytical results on Model II give the speed of translocation by means of a solution of an ordinary differential equation. This speed gives an approximation for the time it takes to translocate a protein of given length.