About a three states molecular evolution model

The Eigen model of molecular evolution has recently been reconsidered by taking into account the existence of non-reproducing sequences. New results obtained with this model are presented here: several time-scales characterize the population dynamics and the location of the error threshold, shifted towards larger values of the probability of mutation, depends on both the size of the population and time. Thus this model can be used to analyse extinction events. The distribution of individuals in sequence space beyond the threshold is also discussed.     

Gap junction ultrastructure in three states of conductance

Summary Junctional conductance between the epidermal cells of the beetle Tenebrio molitor is raised after exposure to the hormone 20-hydroxyecdysone and lowered reversibly by exposure to chlorpromazine. Gap Junctional particle size, density and arrangement associated with these conductance changes were studied. We found no significant difference in particle density in gap junctions of control (2456±471 particles/m², mean ±S.D.) and hormone-treated epidermis (2490±315); however, a significant increase in packing density occurred in chlorpromazine-uncoupled epidermis (3133±665). The particles are randomly arranged in all three states of conductance. Particle size measurements show that the E-face gap junctional particles are heterogeneous with a mean diameter ±S.D. of 15.2±2.0 nm. No significant difference in particle size between controls and experimentals was detected. Although glutaraldehyde irreversibly uncoupled these cells, the absence of glutaraldehyde fixation but presence of glycerol induced marked alterations in the appearance of the gap junctions such that quantification was no longer possible. From this particle-packing data and our previous thin-section data, we estimate that there are 90000 gap junctional particles per cell (within junctional plaques). The conductance of a single gap junctional channel (assuming one population) changes from 94 pS to 213 pS after hormone treatment.     

Heart attacks, heart rate, and gel electrodes: the invention of ambulatory cardiology

Ambulatory cardiology began in 1959 in a department of pathology to answer a question raised at the autopsy table: are high heart rates in apparently healthy individuals a risk factor for developing coronary artery disease? This question led to the development of a miniature monitor and a new kind of electrode, which enabled clinicians to measure EKG signals during activity and over prolonged periods of time. These electrodes are now used universally for diagnosis and for monitoring the heart during a myriad of different activities and circumstances. The story of the development of the monitor and electrodes illustrates the ways in which ideas and discovery lead to applications and advances in medicine.     

Infant and child mortality in three culturally contrasting states of India.

Using cross-sectional, individual-level survey data from Maharashtra, Tamil Nadu and Uttar Pradesh collected under the Indian National Family Health Survey programme of 1992-93, statistical modelling was used to analyse the impact of a range of variables on the survival status of children during their first 2 years of life. Attention was focused on the potential impact of the mother's autonomy. The strongest predictors of mortality were demographic and biological factors, breast-feeding behaviour, and use and knowledge of health services. Variables that can be interpreted as being related to maternal autonomy, such as the presence of a mother-in-law in the household, did not have a significant direct effect on child survival at the individual level, and their indirect effects were very limited.     

The three states of globular proteins: acid denaturation.

We describe statistical mechanical theory that aims to predict protein stabilities as a function of temperature, pH, and salt concentration, from the physical properties of the constituent amino acids: (1) the number of nonpolar groups, (2) the chain length, (3) the temperature-dependent free energy of transfer, (4) the pKa's (including those in the native state) and their temperature dependencies. We calculate here the phase diagrams for apomyoglobin and hypothetical variant proteins. The theory captures essential features of protein stability including myoglobin's Tm vs pH as measured by P. L. Privalov [(1979) Advances in Protein Chemistry, Vol. 33, pp. 167-241] and its ionic strength vs pH phase diagram as measured by Y. Goto and A. L. Fink [(1990) Journal of Molecular Biology, Vol. 214, pp. 803-805]. The main predictions here are the following: (1) There are three stable states, corresponding to native (N), compact denatured (C), and highly unfolded (U), with transitions between them. (2) In agreement with experiments, the compact denatured state is predicted to have enthalpy closer to U than N because even though there is considerable hydrophobic "clustering" in C, this nevertheless represents a major loss of hydrophobic contacts relative to configurations (N) that have a hydrophobic "core." (3) C becomes more prominent in the phase diagram with increasing nonpolar content or decreasing chain length, perhaps thus accounting for (a) why lysozyme and alpha-lactalbumin differ in their denatured states, and (b) why shortened Staph nuclease molecules are compact. (4) Of major importance for protein calorimetry is Privalov's observation that the enthalpy of folding, delta H (T, pH) is independent of pH. The theory accounts for this through the prediction that the main electrostatic contribution to stability is not enthalpic; the main contribution is the entropy, mainly due to the different distributions of protons and small ions in the native and denatured states.     

Enzymes as a subject of invention

A patent-legal situation is analyzed which has arisen in the world in connection with the problem on protection of native enzymes as objects of invention. The objects under study are shown to correspond to the demands of novelty, essential distinctions and positive practical effect which are made by the legislation of the USSR to inventions. Possibility of legal protection of enzymes as substances with unstated structure obtained microbiologically is determined in terms of acting standard statements. A set of characters necessary and sufficient for recognition of enzymes and substantiation of their novelty is suggested for characteristics of enzymes in original papers and patent documents. General approaches to optimization of native enzyme examination for the novelty and essential characteristics are developed.     

Patterns of antennal sensilla of Panstrongylus megistus from three Brazilian states

The objective of the present study was to analyze and describe the phenotype of the antennal sensilla of Panstrongylus megistus, one of the epidemiologically most important species of triatomines in Brazil. Specimens from the Brazilian states of Goiás (GO), Minas Gerais (MG), and Rio Grande do Sul (RS) were compared, based on studies of four types of sensilla on three antennal segments: thick-walled trichoid (TK), thin-walled trichoid (TH), bristles (BR), and basiconica (BA). Discriminant analysis allowed the separation of the RS specimens from those of GO and MG. Multivariate discriminant analysis demonstrated that the sensilla of males differed from those of females, the variables with greatest weight being the BA of all three segments and the TK of flagellum 1. The basiconica sensilla were significantly more abundant in females, on all three segments. Antennal sensilla patterns also demonstrated significant differences among P. megistus specimens.     

Characterization of three regulatory states of the striated muscle thin filament

The troponin-tropomyosin-linked regulation of striated muscle contraction occurs through allosteric control by both Ca(2+) and myosin. The thin filament fluctuates between two extreme states: the inactive "off" state and the active "on" state. Intermediate states have been proposed from structural studies and transient kinetic measurements. However, in contrast to the well-characterised, on and off states, the mechanochemical properties of the intermediate states are much less well understood because of the instability of those states. In the present study, we have characterized a myosin-induced intermediate that is stabilized by cross-linking myosin motor domains (S1) to actin filaments (with a maximum of one S1 molecule for 50 actin monomers). A single S1 molecule is known to interact with two adjacent actin monomers. A detailed analysis revealed that thin filaments containing S1 molecules cross-linked to just one actin monomer (actin(1)-S1 complexes) are regulated with a 79% inhibition of the ATPase in the absence of Ca(2+). In contrast, filaments containing S1 molecules cross-linked at two positions, to two adjacent actin monomers (actin(2)-S1 complexes) totally lose their regulation in a highly cooperative manner. This loss of regulation was due both to an enhancement of the ATPase activity without calcium and an inhibition of the ATPase with calcium. Filaments containing actin(2)-S1 complexes, with significant ATPase activity in the absence of calcium (about 50%), did not move on a myosin-coated surface unless calcium was present. This partial uncoupling between the ATPase activity and in vitro motility in the absence of calcium demonstrates that the mechanical steps require actin-myosin contacts, which take place only in the on state and not in the off or intermediate states. These data provide new insights concerning the difference in cooperativity of Ca(2+) regulation that exists between the biochemical and mechanical cycles of the actin-myosin motor.     

Proton activities for three states of cytochrome P-450cam.

Changes in proton concentration during the binding of dioxygen, carbon monoxide, and for the exchange of dioxygen by carbon monoxide, at ferrous-cytochrome P-450cam were measured by direct titration. Insufficient proton release was observed to support protonation-deprotonation of an axial cysteinyl sulfur donor as a mechanism for generation of hyper spectra in only the carbonylated ferrous state. Measurement of the $\text{P}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ value for CO binding as a function of pH (the carbon monoxide Bohr effect) confirms the direct titration data.     

Animals and the invention of the Phanerozoic Earth system

Animals do not just occupy the modern biosphere, they permeate its structure and define how it works. Their unique combination of organ-grade multicellularity, motility and heterotrophic habit makes them powerful geobiological agents, imposing myriad feedbacks on nutrient cycling, productivity and environment. Most significantly, animals have 'engineered' the biosphere over evolutionary time, forcing the diversification of, for example, phytoplankton, land plants, trophic structure, large body size, bioturbation, biomineralization and indeed the evolutionary process itself. This review surveys how animals contribute to the modern world and provides a basis for reconstructing ancient ecosystems. Earlier, less animal-influenced biospheres worked quite differently from the one currently occupied, with the Ediacaran-Cambrian radiation of organ-grade animals marking a fundamental shift in macroecological and macroevolutionary expression.     

Structures of nitroreductase in three states: effects of inhibitor binding and reduction.

The crystal structure of the nitroreductase enzyme from Enterobacter cloacae has been determined for the oxidized form in separate complexes with benzoate and acetate inhibitors and for the two-electron reduced form. Nitroreductase is a member of a group of enzymes that reduce a broad range of nitroaromatic compounds and has potential uses in chemotherapy and bioremediation. The monomers of the nitroreductase dimer adopt an alpha+beta fold and together bind two flavin mononucleotide prosthetic groups at the dimer interface. In the oxidized enzyme, the flavin ring system adopts a strongly bent (16 degrees ) conformation, and the bend increases (25 degrees ) in the reduced form of the enzyme, roughly the conformation predicted for reduced flavin free in solution. Because free oxidized flavin is planar, the induced bend in the oxidized enzyme may favor reduction, and it may also account for the characteristic inability of the enzyme to stabilize the one electron-reduced semiquinone flavin, which is also planar. Both inhibitors bind over the pyrimidine and central rings of the flavin in partially overlapping sites. Comparison of the two inhibitor complexes shows that a portion of helix H6 can flex to accommodate the differently sized inhibitors suggesting a mechanism for accommodating varied substrates.     

Fritz Jahr: the invention of bioethics and beyond

Since the discovery of his work in 1997, Fritz Jahr (1895-1953) has slowly become recognized as the author of the term and concept of bioethics. Jahr's ideas on bioethics were partly different from those shaped by Van Rensselaer Potter in the 1970s and, therefore, might be helpful for the further reform and broadening of modern bioethics. In this article, the authors elucidate ideas from lesser-known works by Jahr, especially those considering animal protection and teaching.