On the dynamics of a toxicant-individual system

The dynamics of a toxicant-individual model where the individual is represented by von Bertalanffy dynamics and the uptake model component is one developed by Barber, Suarez & Lassiter is discussed. A sufficient condition for the death of an individual subjected to chemical stress is found. Another possible behavior of the system is an oscillatory mode of individual size and internal chemical concentration determined by a limit cycle. These fluctuations are a consequence of formulations of growth, maintenance, and the dose-response functions in the model system.     

Numerical simulation of the electrophoretic transport of a biopolymer through a synthetic nano-pore

We employed a hybrid approach to study numerically the translocation of a biopolymer through an artificial nano-pore driven by an external electric field in the presence of an explicit solvent. The motion of the polymer is simulated by the 3D Langevin dynamics technique. The hydrodynamic interactions (HI) between the polymer and the fluid are taken into account by the lattice Boltzmann equation. Our polymer chain model representing the double-stranded DNA was first validated by comparing the diffusion coefficient obtained from the numerical results with the experimental and theoretical results. Then, we conducted numerical simulations of the biopolymer's translocation process by applying a theoretical formula for the net electrophoretic force acting on the part of the polymer residing in the pore. We compared quantitatively the translocation times and the velocities of different DNA lengths with the corresponding experimental results. Our simulation results are in good agreement with the experimental ones when the HI are considered explicitly.     

Fibrillation of a cardiac region and the tachycardia mode of a two-oscillator system

The interaction between two nonlinear oscillators is discussed, each one representing a region of the heart and characterized by a specific type of phase transition curve (PTC) which has been derived from human ECG-recordings. Besides the normal conduction a tachycardia mode is studied where the excitation is reflected by each oscillator (reentry). It turns out that under specific physiologically plausible conditions this tachycardia mode cannot be terminated by an external stimulus. Under periodic stimulation the response of the tachycardia mode is chaotic. Within a sheet of nonlinear oscillators the tachycardia mode serves as an ectopic focus or a region of reentry which induces fibrillation of the whole tissue.     

Estimation of the Distribution of a Genetically Determined Enzyme Polymorphism by a Stochastical Outside Criterion

The remaining cholinesterase activity after incubation with paraoxon (as an indicator of the activity of human serumparaoxonase) shows a distribution with three clusters which could be explained, after an investigation of families, by a simple two-allele-model. A Stochastical outside criterion is given by the constellations of the values within the families. By modification of an iteration method described by FANGMEYER (1964) it is possible to estimate the distributions and frequencies of the three groups. A simulation study shows that the combination of the used method with the pure cluster analysis is advantageous.     

On the determination of the concentration over a sphere with a barrier layer

Slow synaptic potentials may occur in principle because diffusion of the neurotransmitter to the receptors on the post-junctional cell is impeded by a barrier layer. This possibility can sometimes be tested by examining the time course of responses to an agonist applied at different distances from the cell surface.     

Incorporation of a polypeptide segment into the beta-domain pore during the assembly of a bacterial autotransporter.

Bacterial autotransporters consist of an N-terminal 'passenger domain' that is transported into the extracellular space by an unknown mechanism and a C-terminal 'beta-domain' that forms a beta-barrel in the outer membrane. Recent studies have revealed that fully assembled autotransporters have an unusual architecture in which a small passenger domain segment traverses the pore formed by the beta-domain. It is unclear, however, whether this configuration forms prior to passenger domain translocation or results from the translocation of the passenger domain through the beta-domain pore. By examining the accessibility of tobacco etch virus protease sites and single-cysteine residues in the passenger domain of the Escherichia coli O157:H7 autotransporter EspP at different stages of protein biogenesis, we identified a novel pre-translocation intermediate whose topology resembles that of the fully assembled protein. This intermediate was isolated in the periplasm in cell fractionation experiments. The data strongly suggest that the EspP beta-domain and an embedded polypeptide segment are integrated into the outer membrane as a single pre-formed unit. The data also provide indirect evidence that at least some outer membrane proteins acquire considerable tertiary structure prior to their membrane integration.     

Optical properties of a plasma produced by the tunneling ionization of atoms of a matter in the field of a circularly polarized wave

General features of the absorption and reflection of a test wave by a nonequilibrium plasma produced in the tunneling ionization of atoms of a matter by a circularly polarized laser pulse are described. Because of the highly anisotropic distribution of photoelectrons, the optical properties of a nonequilibrium plasma differ considerably from those of a plasma with a Maxwellian electron velocity distribution. Physically, an anomalous behavior of the absorption coefficient and of the phase shift stems from the fact that electron kinetics in the skin layer is modified by the alternating magnetic field of the test wave.     

Collapse of a polypeptide chain as a result of the intramolecular formation of antiparallel beta-sheets

The folded nature of an intramolecular antiparallel β-sheet suggests that the introduction of this structure into a statistical coil might be accompanied by a contraction of the chain. The magnitude of the contraction, and the conditions that produce the maximum contraction, have been assessed by the combination of generator matrices with an earlier formulation for the configuration partition function. The results show that the mean square dimensions do indeed pass through a minimum upon the transition from a statistical coil to an antiparallel β-sheet. The depth of the minimum is relatively insensitive to the values of δ and τ, provided the assignments are within the physically sensible range. (The borders of the ordered region are assumed to be of higher energy than the interior.) In contrast with the depth of the minimum, the β-sheet content that produces the minimum is quite sensitive to plausible variation in δ and τ. A much greater collapse of the chain can be produced by antiparallel β-sheet formation than that found in the course of the helix–coil transition. The collapse may cause the volume pervaded by the chain to come within an order of magnitude of the volume characteristic of the globular state.     

The effect of error fields on the dynamics of a tearing mode in a tokamak

The features of the tearing mode dynamics in a tokamak that manifest themselves in an irregular mode rotation are demonstrated by using an algorithm for data processing that is based on the concept of the instantaneous frequency of an analytic signal. A model is developed in which the tearing mode is treated as an object to be controlled by means of an external quasistatic magnetic field with an appropriate spatial structure. It is shown that the model dynamics of the mode agrees well with the dynamics of tearing modes observed in experiments in which they are influenced by the magnetic field of the halo current.     

Replacement of a phosphoenolpyruvate-dependent phosphotransferase by a nicotinamide adenine dinucleotide-linked dehydrogenase for the utilization of mannitol

Mannitol is dissimilated by Aerobacter aerogenes via an inducible pathway initiated by a phosphotransferase system dependent upon phosphoenolpyruvate as the phosphoryl donor. A mutational block in this pathway can be suppressed either at the phenotypic level by induction of d-arabitol dehydrogenase, an enzyme fortuitously capable of converting mannitol to fructose, or genotypically by a constitutive mutation in the d-arabitol system.     

Augmentation is a potentiation of the exocytotic process

Short-term synaptic enhancement is caused by an increase in the probability with which synaptic terminals release transmitter in response to presynaptic action potentials. Since exocytosed vesicles are drawn from a readily releasable pool of packaged transmitter, enhancement must result either from an increase in the size of the pool or an elevation in the fraction of releasable vesicles that undergoes exocytosis with each action potential. We show here that at least one major component of enhancement, augmentation, is not caused by an increase in the size of the readily releasable pool but is instead associated with an increase in the efficiency with which action potentials induce the exocytosis of readily releasable vesicles.     

Toward the engineering of a super efficient enzyme

The catalytic activity of a mutant of Photobacterium leiognathi Cu, Zn superoxide dismutase in which the Glu59 residue, conserved in most bacterial variants of the enzyme, has been replaced by glutamine was investigated by pulse radiolysis. At neutral pH the enzyme was found to have a kcat/KM of 1.0 +/- 0.1 x 10(10) M-1s-1 the highest value ever found for any superoxide dismutase. Brownian dynamics simulation suggests that such a high value is due to an enhanced substrate attraction by the modified electric field distribution. The mutant is also characterized by an active-site widely accessible for the solvent, since iodide is able to interact with the copper atom with an affinity constant twice as high as that found in the native enzyme. The large solvent accessible surface of the copper site together with a favorable distribution of the protein-generated electric field gives rise to the most efficient enzyme ever found with activity close to the diffusion limit.     

On the theory of Cherenkov emission in a plasma

The Cherenkov emission of transverse-longitudinal waves in an anisotropic plasma is considered by applying a Hamiltonian method and by drawing an analogy between the equations for the Cherenkov emission of purely transverse and purely longitudinal waves in isotropic media and the equations for the emission of transverse-longitudinal electromagnetic waves in a highly anisotropic medium (a magnetized plasma). A formula for the emitted power is derived, as well as an expression for the directional pattern of the emitted waves in an anisotropic plasma.     

A Note on the Development of a Technique for Regeneration of a Degenerated Culture

In a heterogeneous degenerated culture the method of in situ screening of established agar colonies (the number screened being limited) cannot reveal the presence of an antibiotic-producing organism even after mutagenic treatment, whereas the close-range parallel streak method can succeed. Streaking a pour-plate culture of an antibiotic-sensitive organism by parallel streaks of mutagen-treated inactive culture of the once producer afforded a better chance for regeneration of a degenerated culture.     

Vitrosin: a member of the collagen class

Vitrosin, a fibrous protein obtained from the vitreous humor of the eye in the form of an indefinitely long fibril about 100 to 150 A in diameter, has been identified as a member of the collagen class of proteins. It is characterized by the collagen wide-angle x-ray diffraction pattern, and axial periodicity of about 640 A determined by electron microscopy and small-angle x-ray diffraction, an amino acid pattern characteristic of collagen as determined by paper chromatography, and a hydroxyproline and glycine content also typical of collagen. The glycine-hydroxyproline ratio is somewhat lower than that for most vertebrate collagens.     

Evolution of a multigene family that encodes the Kunitz chymotrypsin inhibitor in winged bean: a possible intermediate in the generation of a new gene with a distinct pattern of expression

Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates in an organ-specific and temporally regulated manner. The protein is encoded by a multigene family that includes at least four putative inhibitor-coding genes and three pseudogenes. The structure of the WCI genes indicates that an insertion at a 5′ proximal site occurred after duplication of the ancestral WCI gene and that several gene conversion events subsequently contributed to the evolution of this gene family. Analysis of the promoter activity of the 5′ regions of the WCI genes in transgenic tobacco showed that only the 5′ regions of the WCI-3a and WCI-3b genes, which encode the major WCI protein in winged bean, promoted the organ-specific and temporally regulated expression of a reporter gene. The 5′ region of a pseudogene, the WCI-P1 gene which contains frameshift mutations, exhibited constitutive promoter activity in tobacco, an indication that the 5′ region of the WCI-P1 gene might spontaneously have acquired new regulatory sequences during evolution. Since gene conversion is a relatively frequent event and since the homology between the WCI-P1 and WCI-3a/b genes is disrupted at a 5′ proximal site by remnants of an inserted sequence, the WCI-P1 gene appears to be a possible intermediate that could be converted into a new functional gene with a distinct pattern of expression by a single gene-conversion event. Received: 17 April 1996 / Accepted: 23 October 1996     

Determination of the genotoxic status of a chemical

Before a non-genotoxic mechanism of action is proposed for a rodent carcinogen, or predicted for an untested chemical, adequate knowledge of the genotoxic status of the chemical must exist. The current absence of absolute agreement on the set of assays to use when evaluating genotoxicity suggests that a practical approach should be adopted, as outlined, for example, by Arni et al. (1988). In that approach, the chemical is evaluated for gene mutagenicity to Salmonella, for its ability to induce chromosomal aberrations in cultured mammalian cells, and if appropriate, gene mutations in cultured mammalian cells. Consideration of the chemical structure and the expected metabolism of the test chemical also contribute to the classification of an agent as a putative non-genotoxin. Judgement is required when interpreting isolated positive test responses generated in peripheral short-term tests. When attempting to study the mode of action of an established rodent carcinogen that is thought to operate by a non-genotoxic mechanism of action, genotoxicity data generated in vivo, if possible in the target tissue, are of great value. Compounds defined as non-genotoxic by these methods then become candidates for the study of those non-genotoxic toxicities that may predict or explain non-genotoxic rodent carcinogenesis.     

Fast ignition upon the implosion of a thin shell onto a precompressed deuterium-tritium ball

Fast ignition of a precompressed inertial confinement fusion (ICF) target by a hydrodynamic material flux is investigated. A model system of hydrodynamic objects consisting of a central deuterium-tritium (DT) ball and a concentric two-layer shell separated by a vacuum gap is analyzed. The outer layer of the shell is an ablator, while the inner layer consists of DT ice. The igniting hydrodynamic flux forms as a result of laser-driven acceleration and compression of the shell toward the system center. A series of one-dimensional numerical simulations of the shell implosion, the collision of the shell with the DT ball, and the generation and propagation of thermonuclear burn waves in both parts of the system are performed. Analytic models are developed that describe the implosion of a thin shell onto a central homogeneous ball of arbitrary radius and density and the initiation and propagation of a thermonuclear burn wave induced by such an implosion. Application of the solution of a model problem to analyzing the implosion of a segment of a spherical shell in a conical channel indicates the possibility of fast ignition of a spherical ICF target from a conical target driven by a laser pulse with an energy of 500?C700 kJ.     

Bcs1, a AAA protein of the mitochondria with a role in the biogenesis of the respiratory chain

The family of AAA+ proteins in eukaryotes has many members in various cellular compartments with a broad spectrum of functions in protein unfolding and degradation. The mitochondrial AAA protein Bcs1 plays an unusual role in protein translocation. It is involved in the topogenesis of the Rieske protein, Rip1, and thereby in the biogenesis of the cytochrome bc(1) complex of the mitochondrial respiratory chain. Bcs1 mediates the export of the folded FeS domain of Rip1 across the mitochondrial inner membrane and the insertion of its transmembrane segment into an assembly intermediate of the cytochrome bc(1) complex. We discuss structural elements of the Bcs1 protein compared to other AAA proteins in an attempt to understand the mechanism of its function. In this context, we discuss human diseases caused by mutations in Bcs1 that lead to different properties of the protein and subsequently to different symptoms.     

Generation of the BfiI restriction endonuclease from the fusion of a DNA recognition domain to a non-specific nuclease from the phospholipase D superfamily

The BfiI endonuclease cleaves DNA at fixed positions downstream of an asymmetric sequence. Unlike other restriction enzymes, it functions without metal ions. The N-terminal half of BfiI is similar to Nuc, an EDTA-resistant nuclease from Salmonella typhimurium that belongs to the phosphoplipase D superfamily. Nuc is a dimer with one active site at its subunit interface, as is BfiI, but it cuts DNA non-specifically. BfiI was cleaved by thermolysin into an N-terminal domain, which forms a dimer with non-specific nuclease activity, and a C-terminal domain, which lacks catalytic activity but binds specifically to the recognition sequence as a monomer. On denaturation with guanidinium, BfiI underwent two unfolding transitions: one at a relatively low concentration of guanidinium, to a dimeric non-specific nuclease; a second at a higher concentration, to an inactive monomer. The isolated C-terminal domain unfolded at the first (relatively low) concentration, the isolated N-terminal at the second. Hence, BfiI consists of two physically separate domains, with catalytic and dimerisation functions in the N terminus and DNA recognition functions in the C terminus. It is the first example of a restriction enzyme generated by the evolutionary fusion of a DNA recognition domain to a phosphodiesterase from the phospholipase D superfamily. BfiI may consist of three structural units: a stable central core with the active site, made from two copies of the N-terminal domain, flanked by relatively unstable C-terminal domains, that each bind a copy of the recognition sequence.