Generalized quasispecies model on finite metric spaces: isometry groups and spectral properties of evolutionary matrices

The quasispecies model introduced by Eigen in 1971 has close connections with the isometry group of the space of binary sequences relative to the Hamming distance metric. Generalizing this observation we introduce an abstract quasispecies model on a finite metric space X together with a group of isometries \(\Gamma \) acting transitively on X. We show that if the domain of the fitness function has a natural decomposition into the union of tG-orbits, G being a subgroup of \(\Gamma \), then the dominant eigenvalue of the evolutionary matrix satisfies an algebraic equation of degree at most \(t\cdot \mathrm{rk}_{\mathbf {Z}} R\), where R is the orbital ring that is defined in the text. The general theory is illustrated by three detailed examples. In the first two of them the space X is taken to be the metric space of vertices of a regular polytope with the natural “edge” metric, these are the cases of a regular m-gon and of a hyperoctahedron; the final example takes as X the quotient rings \(\mathbf {Z}/p^n\mathbf {Z}\) with p-adic metric.

     

Membrane binding motif of the P-type cardiotoxin

Carditoxins (CTXs) from cobra snake venoms, the basic 60-62 residue all-beta sheet polypeptides, are known to bind to and impair the function of cell membranes. To assess the membrane induced conformation and orientation of CTXs, the interaction of the P-type cardiotoxin II from Naja oxiana snake venom (CTII) with perdeuterated dodecylphosphocholine (DPC) was studied using ( 1 )H-NMR spectroscopy and diffusion measurements. Under conditions where the toxin formed a well-defined complex with DPC, the spatial structure of CTII with respect to the presence of tightly bound water molecules in loop II, was calculated using the torsion angle dynamics program DYANA. The structure was found to be similar, except for subtle changes in the tips of all three loops, to the previously described "major" form of CTII in aqueous solution illustrated by the "trans" configuration of the Val7-Pro8 peptide bond. No "minor" form with the "cis" configuration of the above bond was found in the micelle-bound state. The broadening of the CTII backbone proton signals by 5, 16-doxylstearate relaxation probes, together with modeling based on the spatial structure of CTII, indicated a periphery mode of binding of the toxin molecule to the micelle and revealed its micelle interacting domain. The latter includes a hydrophobic region of CTII within the extremities of loops I and III (residues 5-11, 46-50), the basement of loop II (residues 24-29,31-37) and the belt of polar residues encircling these loops (lysines 4,5,12,23,50, serines 11,46, histidine 31, arginine 36). It is suggested that this structural motif and the mode of binding can be realized during interaction of CTXs with lipid and biological membranes.     

alpha-Neurotoxins and alpha-conotoxins--nicotinic cholinoreceptor blockers

The review is devoted to the competitive blockers of different nicotinic acetylcholine receptors, alpha-neurotoxins from snake venoms, and alpha-conotoxins from marine snails of the Conidae family. The relationship between the structure and function of these toxins is discussed. Recent data on the mechanism of alpha-neurotoxin and alpha-conotoxin interaction with the nicotinic acetylcholine receptor are presented.     

Large-scale determination of the methylation status of retrotransposons in different tissues using a methylation tags approach

A technique for simultaneous determination of the methylation status of numerous loci containing retroelements (REs) is reported. It is based on the observation that methylated and unmethylated areas in the genome are usually extended, and therefore the methylation of particular methyl-sensitive restriction endonuclease recognition sites might reflect the methylation status of DNA regions around them. The method includes dot-blot hybridization of repeat flanking sequences arrayed on a solid support with specifically amplified flanking regions of presumably unmethylated repeats. A multitude of flanking regions of REs adjacent to unmethylated restriction sites are amplified simultaneously, providing a complex hybridization probe. The technique thus allows the determination of the methylation status of restriction sites, which serve as tags of the methylation status of the surrounding regions. The validity of the technique was confirmed by various means, including bisulfite sequencing. The technique was successfully applied to the identification of methylation patterns of the regions surrounding 38 human-specific HERV-K(HML-2) long terminal repeats in cerebellum- and lymph node-derived genomic DNAs. The described technique can be readily adapted to the use of DNA microarray technology.     

Comparison of methods for the identification of coagulase-negative staphylococci

Coagulase-negative staphylococci (CNS) species identification is still difficult for most clinical laboratories. The scheme proposed by Kloos and Schleifer and modified by Bannerman is the reference method used for the identification of staphylococcal species and subspecies; however, this method is relatively laborious for routine use since it requires the utilization of a large number of biochemical tests. The objective of the present study was to compare four methods, i.e., the reference method, the API Staph system (bioMérieux) and two methods modified from the reference method in our laboratory (simplified method and disk method), in the identification of 100 CNS strains. Compared to the reference method, the simplified method and disk method correctly identified 100 and 99% of the CNS species, respectively, while this rate was 84% for the API Staph system. Inaccurate identification by the API Staph method was observed for Staphylococcus epidermidis (2.2%), S. hominis (25%), S. haemolyticus (37.5%), and S. warneri (47.1%). The simplified method using the simple identification scheme proposed in the present study was found to be efficient for all strains tested, with 100% sensitivity and specificity and proved to be available alternative for the identification of staphylococci, offering, higher reliability and lower cost than the currently available commercial systems. This method would be very useful in clinical microbiology laboratory, especially in places with limited resources.     

DNA structure and dynamics

This review primarily outlines the most recent atomic force microscopy (AFM) studies of DNA structure and dynamics. Sample preparation techniques allowing reliable and reproducible imaging of various DNA topologies are reviewed. Such important issues as imaging of supercoiled DNA conformations at different ionic conditions and detection of local alternative structures that are stabilized by negative DNA supercoiling are discussed in length in the article. The possibility of imaging DNA structural dynamics at different levels is another major focus of the article. Using time-lapse AFM imaging mode of nondried samples, such extensive DNA dynamic processes as transition of one local structure into another (H-DNA to B-form transition), the conformational transitions of DNA Holliday junctions and their branch migration were observed. Potential future applications of this single-molecule dynamics mode of AFM to analyses of various biochemical processes involving DNA are discussed.     

Molecular characterization of the <Emphasis Type="Italic">singed wings</Emphasis> locus of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

Hormones frequently guide animal development via the induction of cascades of gene activities, whose products further amplify an initial hormonal stimulus. In Drosophila the transformation of the larva into the pupa and the subsequent metamorphosis to the adult stage is triggered by changes in the titer of the steroid hormone 20-hydroxyecdysone. singed wings (swi) is the only gene known in Drosophila melanogaster for which mutations specifically interrupt the transmission of the regulatory signal from early to late ecdysone inducible genes.