Abstract: We propose a spatial structure for the tricarboxylic acid cycle enzyme complex (tricarboxylic acid cycle metabolon). The structure is based on an analysis of data on the interaction between tricarboxylic acid cycle enzymes and the mitochondrial inner membrane, as well as on data on enzyme-enzyme interactions. The alpha-ketoglutarate dehydrogenase complex, adsorbed along one of the 3-fold symmetry axes of the mitochondrial inner membrane, plays a key role in formation of the metabolon. In the interaction with the membrane, two association sites of the alpha-ketoglutarate dehydrogenase complex participate, placed on opposite sides of the complex. The tricarboxylic acid cycle enzyme complex contains one molecule of the alpha-ketoglutarate dehydrogenase complex and six molecules of each of the other enzymes of the tricarboxylic acid cycle, as well as aspartate aminotransferase and nucleoside-diphosphate kinase. Succinate dehydrogenase, which is the integral protein of the mitochondrial inner membrane, is a component of the anchor site responsible for the assembly of the metabolon on the membrane. The molecular mass of the complex (without regard to succinate dehydrogenase) is 8 x 10(6) Da. The metabolon symmetry corresponds to the D3 point symmetry group.

Abstract: Three components of a brain model operating on neuromolecular computing principles are described. The first component comprises neurons whose input-output behavior is controlled by significant internal dynamics. Models of discrete enzymatic neurons, reaction-diffusion neurons operating on the basis of the cyclic nucleotide cascade, and neurons controlled by cytoskeletal dynamics are described. The second component of the model is an evolutionary learning algorithm which is used to mold the behavior of enzyme-driven neurons or small networks of these neurons for specific function, usually pattern recognition or target seeking tasks. The evolutionary learning algorithm may be interpreted either as representing the mechanism of variation and natural selection acting on a phylogenetic time scale, or as a conceivable outogenetic adaptation mechanism. The third component of the model is a memory manipulation scheme, called the reference neuron scheme. In principle it is capable of orchestrating a repertoire of enzyme-driven neurons for coherent function. The existing implementations, however, utilize simple neurons without internal dynamics. Spatial navigation and simple game playing (using tic-tac-toe) provide the task environments that have been used to study the properties of the reference neuron model. A memory-based evolutionary learning algorithm has been developed that can assign credit to the individual neurons in a network. It has been run on standard benchmark tasks, and appears to be quite effective both for conventional neural nets and for networks of discrete enzymatic neurons. The models have the character of artificial worlds in that they map the hierarchy of processes in the brain (at the molecular, neuronal, and network levels), provide a task environment, and use this relatively self-contained setup to develop and evaluate learning and adaptation algorithms.

Abstract: In eukaryotic cells, protein biosynthesis is controlled at the level of polypeptide chain initiation. During the initiation process, eukaryotic initiation factor 2 (eIF-2) catalyzes the binding of Met-tRNA f and GTP to the 40S ribosomal subunit. In a later step, eIF-2 is released from the ribosomal initiation complex, most likely as an eIF-2 · GDP complex, and another initiation factor termed eIF-2B is necessary to recycle eIF-2 by displacing GDP by GTP. In rabbit reticulocytes, inhibition of protein synthesis is accompanied by the phosphorylation of the α-subunit of eIF-2, a process that does not render eIF-2 inactive, but prevents it from being recycled by eIF-2B. First described in rabbit reticulocytes as inhibitors of translation, two distinct eIF-2α kinases are known: the haemin-controlled kinase (termed HCI) and the double-stranded RNA-activated kinase (termed DAI). eIF-2α phosphorylation appears to be a reversible control mechanism since corresponding phosphatases have been described. Recent reports indicate a correlation between eIF-2α phosphorylation and the inhibition of protein synthesis in several mammalian cell types under a range of physiological conditions. In this review, the physical and functional features of the known eIF-2α kinases are described with respect to their role in mammalian cells and the mode of activation by cellular signals. Furthermore, the possible impact of the eIF-2/eIF-2B ratio and of the subcellular compartmentation of these factors (and the eIF-2α kinases) on mammalian protein synthesis is discussed.

Abstract: Discrete-time growth-dispersal models readily exhibit diffusive instability. In some instances, this diffusive instability parallels that found in continuous-time reaction-diffusion equations. However, if a sufficiently eruptive prey is held in check by a predator, predator overdispersal may also lead to one or a series of diffusion-driven period-doubling bifurcations. Quite common discrete-time predator-prey models exhibit this new brand of diffusive instability.

Abstract: The only epistemic relations between the world and organisms are established through evolution by natural selection, and learning by observation and measurement. In physics, measurements map an open domain of physical structure to a closed set of symbols. A basic problem in simulating evolution and measurement is that neither activity can be adequately formalized. Artificial world models based on programmable computers require a formalized domain of symbols in which the concepts of evolution and measurement are limited. The measurement problem also bears on the questions of the relation of computation to physics and to formal symbol systems and on what sense dissipationless computation is a useful concept.

Abstract: Cyclic nucleotide injection in neurons shows that cAMP controls a new type of membrane permeability. The neuron response to cAMP has a short delay, unusual bioenergetics and is blocked by drugs binding with the regulatory subunit of protein kinase. These data are interpreted in terms of the hypothesis that the controlling system of the living cell is a molecular (DNA, RNA, protein operators with complementary addresses), holographic (quick changeable lattice--cytoskeleton), quantum (each phonon examines whole lattice), hypersound (with wave length 100-10,000 A that does not destroy molecules) system with an inner point of view (molecular coding of questions and answers about quantum processing). Neither an electron, nor a macroscopic computer has an inner point of view.

Abstract: The mathematical relations developed by various researchers for the oxygen dissociation curve are reviewed. Using well-known mechanisms of chemical kinetics of various species in the blood, we have developed a mathematical formula to compute the oxygen dissociation curve in the blood showing its dependence on the pH and PCO2. The functional form, proposed here, is much simpler in comparison to those available in the literature for use in the mathematical modelling of O2 transport in the pulmonary and systemic circulations. In the process, the well-known Hill's equation has been generalized showing an explicit dependence on PCO2 and pH. It is shown that the oxygen dissociation curve computed from our comparatively simpler equation, fits in fairly well with the documented data and shows realistic shift with PCO2 and pH.

Abstract: The genus Ginkgo is a north temperate gymnosperm taxon represented by fossilized leaves and wood from the early Jurassic through the Pliocene, and by the living species G. biloba native to eastern China. Seeds produced by this widely cultivated tree consist of an odoriferous, vesicatory coat surrounding a hard-shelled “nut.” Dispersal of ginkgo seeds is a two step process: repulsion of predators by the toxic coat, followed by attraction of dispersers by the edible “nut.” Based on anatomical and distributional evidence, extinct mammalian multituberculates in the genus Ptilodus are plausible consumers and dispersers of ginkgo seeds during the Paleocene and the Eocene. From the Oligocene through Pleistocene, seed-caching rodents are the most likely dispersal agents of ginkgo. Among extant genera in the class Coniferopsida which produce fleshy, animal-dispersed seeds, there appear to be two distinct evolutionary lines: (1) those with relatively large (> 20 mm), odoriferous diaspores dispersed primarily by mammals; and (2) those with relatively small (< 10 mm), visually attractive diaspores dispersed primarily by birds.

Abstract: A temporary flagellate (mastigote) stage has been observed in several isolates of the vahlkampfiid amoeba Willaertia magna In an Australian isolate studied in detail, flagellates appeared synchronously, although later than in Naegleria fowleri or N lovaniensis under similar conditions (half-maximal time, t50 = 168 min at 37°C) The flagellates initially have four flagella and lack a cytostome, but undergo several successive divisions, the first of them synchronous, resulting in progressive reduction in cell volume New flagella appear during and after division, and the number of flagella in daughter cells of later divisions is rather variable Comparison of these observations with descriptions of other amoeboflagellates confirms that Willaertia is a valid genus A likely sequence of morphological changes in the evolution of Willaertia and Naegleria from a hypothetical ancestral vahlkampfiid is proposed

Abstract: Artificial worlds models of evolutionary systems are computer models that map the essential logical structure of ecological systems, defined as self-sustaining biological organizations. The artificial world comprises an artificial environment, with mass components, energy input, and physical states. It also comprises artificial organisms, including a genome, a phenome, and a (developmental) map that connects the genome to the phenome. Mass components are cycled and space is limited. The evolution process results, as in nature, from genetic variation combined with natural selection imposed by the finiteness of the environment. The selection criteria (fitness values) are not imposed, but rather emerge from the interactions of the organisms with each other and with the environment. The dynamics at the population level also emerges from these basic interactions. In this paper we describe the comparative properties of the EVOLVE family of artificial worlds models.

Abstract: The evolutionary variations of nuclear structure of animals, plants, fungi and protoctists were studied with electron microscopy by using techniques preferentially staining ribonucleoprotein (RNP) particles and chromatin. A remarkable similarity in the general morphological features of the RNP particles and chromatin arrangement is found in animals, plants and fungi. Important variations of these features were found in protoctists. These observations suggest that major evolutionary changes in the nuclear structure predate the acquisition of plastids by the ancestors of green plants. Once evolved, the nuclear structural pattern is conserved in plants and animals. Among protoctists studied, Kinetoplastida, Cryptomonadida and Volvocida have RNP particles and chromatin arrangement resembling those of plants and animals. These similarities may indicate a common ancestor. Important differences in the nuclear structure among Euglenida, Amebida, Cryptomonadida, Volvocida and Kinetoplastida support the view that Sarcomastigophora is a polyphyletic taxon. For the same reason Kinetoplastida and Euglenida must not be grouped in a monophyletic taxon. We propose that the variations of RNP particles may be related to the initial evolution of post-transcriptional processing.

Abstract: The oscillatory state of glycolysis in yeast extracts has been analysed by methods known from electronic circuit studies. The time course of the reactions are calculated by the method of least squares from experimentally determined sets of the concentrations of most of the metabolites. The dynamics of the glycolytic network of reactions can then be represented in terms of flow versus driving force (current versus voltage in the corresponding electronic circuit). The analysis of the dynamics leads to the conclusion that glycolysis is switched on and off in a pulsed manner during the oscillatory state. The resulting pulsed flow cannot only be measured with glycolytic end products, like carbon dioxide or ethanol, but can also readily be demonstrated by diagrams of reaction rates of single enzymic steps even in the initial stages of the glycolytic sequence. An analytic method widely applied to electronic circuits also proved to be useful in the study of the dynamics of a complex enzymic network.

Abstract: The bending motions of an ATP-activated actin filament and a flagellar axoneme of starfish spermatozoon exhibit a one-to-many correspondence between the displacement of the medium and the force actualized in the medium, demonstrating sharp contrast to the one-to-one correspondence in classical mechanics. Uniqueness of the actualized forces is lacking. Cell motility suggests the absence of a completely specifiable boundary condition that would unambiguously control the dynamics of generating mechanical forces in motile cells. The one-to-many relationship between the displacement of the medium and the force actualized in the medium necessitates a materialistic capacity for making choices on the part of molecules and cells in transforming future possibilities into actualized reality, the latter of which again serves as the source of the further future possibilities.

Abstract: In living organsims 20 amino acids along with the terminator value(s) are encoded by 64 codons giving a degeneracy of the codons as described by the genetic code. A basic theoretical problem of genetic codes is to explain the particular distribution of degeneracies of partitions involved in the codes. In this work the degeneracy problem is considered in the framework of information theory. It is shown by direct numerical evaluation of a certain degeneracy information function associated with the genetic code that the degeneracy of the codes is observed to be related to the optimization of this function.

Abstract: The scientific simplicity principle (OCCAM's razor) has always been strongly enforced by the available modelling tools. Moreover, the concept of simplicity itself is shaped by these (classical) tools. Computer models are less subject to simplicity constraints than other models are. It may be argued that complexity is the preeminent property for biological systems to study. In this paper we discuss our MIRROR modelling methodology in which (a concept of) simplicity is reconciled with biological complexity. Simplicity resides in the simple "TODO" ("do what there is to do") of the "individuals" (molecules, cells, organisms) which inhabit the model universe. The complexity appears in the multiple (levels of) individuals and the multiple levels of observable behavior of the universe. Examples are given of the development of complex, self-regulating social structures by simple interactions of individuals, and the adaptability of TODO based entities is compared to that of evolving entities. On the basis of these examples we sketch a slightly unconventional image of the evolution of complexity in biotic systems and discuss observations on the molecular record of biotic evolution which seem to fit this image.

Abstract: In biological systems, the processing and use of information has evolved out of the need for survival in the face of an uncertain environment. As a consequence, the information-function relationship in these systems is shaped by their adaptability characteristics. In contrast, the information-function relationship in man-designed, goal-oriented organizational systems depends on the ability of the information processing system to support the achievement of the organization's goals. In this paper we use results from adaptability theory in the analysis of control-related aspects of the information-function relationship in man-designed organizational systems. In particular, we use a conceptual model of organizational control to characterize features of functional and control structures and their effect on the adaptability of these systems. The concept of implicit control and a design principle for adaptability-enhancing information systems are derived for this analysis.

Abstract: Metopus contortus (Class Spirotrichea), Cyclidium borrori, Cyclidium sp., Sonderia tubigula, and two other species of Sonderia (Class Oligohymenophorea) were enriched from the sulfureta of microbial mat communities at Laguna Figueroa near San Quintin, Baja California, Mexico. The ability of some of these species to grow under anaerobic, high-sulfide conditions was demonstrated. The ultrastructural morphology of Metopus and Cyclidium revealed adaptations to anaerobic, high sulfide niches. Metopus lacks typical mitochondria and has structures which may be intracellular bacterial symbionts. Cyclidium borrori, when grown aerobically, has mitochondria with tubular cristae. When it is grown anaerobically in the presence of high amounts of hydrogen sulfide the number of mitochondria remains the same but the mitochondria dedifferentiate, becoming smaller with less well-defined cristae.

Abstract: We previously showed with computer simulations that cyclic enzyme systems have the reliability of ON-OFF types of operation (McCulloch-Pitts' neuronic equation) and the applicability for a switching circuit in a biocomputer. The switching time was inevitably determined in accordance with the difference in amount between two inputs of the system. This characteristic is, however, a disadvantage for practical use of a switching device; we need to improve the system in order for the switching time to optionally be changed. We shall present here how to turn on (off) the switch independently of the modes of two inputs. By introducing pulse perturbation, we could optionally set up the switching time of a cyclic enzyme system (biochemical switching device).

Abstract: Photochemical activity as well as some spectral properties of various porphyrins and their model complexes with proteinoids were studied. Photochemical activity increased from the less advanced biosynthetic chlorophyll precursors to the more advanced compounds. The significant increase was detected as a result of the formation of complexes of phytol-containing porphyrins with proteinoids, which brings about the disaggregation of the pigment clusters formed in the aqueous environment. Hemin is photochemically inactive, either alone or in complex with proteinoid. Although hemoproteinoid was demonstrated to be able to catalyse photochemical electron transfer, its activity is about 20 times lower when compared with the chlorophyll a-proteinoid complex. Experimental results are discussed in context of the early evolution of photosynthesis.

Abstract: The interrelations of physics and biology are discussed. It is shown that Darwin can be considered as one of the founders of the important field of contemporary physics called physics of dissipative structures or synergetics. The theories of gradual and punctual evolution are presented. The contradiction between these theories can be solved on the basis of molecular theory of evolution and on the basis of the phenomenological physical treatment. The general physical properties of living systems, considered as open systems being far from equilibrium, are listed and simple non-linear mathematical models describing gradual and punctual speciation are suggested. The usual pictures which present these two kinds of speciation can possess physico-mathematical sense. Punctuated speciation means bifurcation, a kind of non-equilibrium phase transition.

Abstract: Community models with competition and mutualism are qualitatively analyzed using the methodology of loop analysis combined with computer stochastic simulation. The concept of “moving equilibrium” in the growth rate of the species is discussed in 14 “tables of predictions”, presented as analytical tools that can help to shed light on controversial ecological issues such as direct versus indirect interaction and positive feedback effects on stability. While the stochastic simulation shows that only little or no difference exists in probability of stability between models with competition and models with mutualism, the related tables of predictions show that the networks among links are able to activate indirect interactions, with both negative and positive effects, between any pair of species. This phenomenon makes it difficult to determine how much stability is related to the direct interactions.

Abstract: A highly simplified evolving system was investigated by computer simulation. The genetic complement of each simulated organism in the population was represented by a single chromosome that consisted of a string of symbols. Individual fitness was measured as the number of symbols that corresponded to a specified rule. Reproduction was simulated with a non-breeding algorithm and two variants of a breeding algorithm, and was subject to random point mutations. In each generation, selection was effected by replacing the less fit members of the population with offspring of the more fit. The size of the population and the fraction replaced, though under experimental control, were constant for each simulation run. It was found that even such a simplified system is able to mimic a variety of properties observed in natural systems. In addition, the effect of the simulation parameters on the course of fitness increase provides a basis for using a genetic algorithm as an optimization technique.

Abstract: The process of gas exchange in systemic capillaries and its surrounding tissue is simulated numerically in a hyperbaric environment, taking into account the molecular diffusion, convection, saturation of haemoglobin with O2 and CO2, and the metabolic activity in the tissue. Krogh tissue-cylinder is used as a geometrical representation of the capillary-tissue system. The resulting system of non-linear governing equations together with the physiologically relevant boundary conditions is solved numerically. It is found that the concentration of oxygen decreases from the axis of the capillary to the tissue periphery whereas the concentration of carbon dioxide increases. It is shown that very little CO2 is transported radially. The location of the vulnerable region from the point of view of CO2 accumulation is found to be the rim (r = R2, z = L) situated at the periphery of the tissue near the venous end of the capillary. It is also found that accumulation of O2 decreases whereas that of CO2 increases in a hyperbaric environment. Finally, it is surmised that one of the reasons in causing discomfort among divers could be excessive accumulation of CO2 in the tissue.

Abstract: It is thought that an important function of protein turnover is to purge the cell of damaged, displaced or unwanted polypeptide molecules. A model combining kinetic equations for synthesis, degradation and alteration is employed to evaluate this proposed role for protein turnover. It is demonstrated that the degradative system need not be aimed exclusively at altered protein molecules for turnover to be capable of controlling the size both of the total population and of the altered subpopulation. These conclusions are relevant to the part played by turnover in metabolic homeostasis, adaptation and catastrophe, and for the notion of control of protein turnover through specific “tagging” of molecules destined for breakdown.

Abstract: A model is described which simulates activation of glycogen phosphorylase and induction of trehalose synthesis in the fat body of the American cockroach, Periplaneta americana , by two hypertrehalosaemic peptides. Parameters for the model were estimated from literature data (Siegert et al., Insect Biochem. 16, 365), with the exception of the half-life of the physiologically active peptides, which was estimated from the model. The model describes satisfactorily the activation of glycogen phosphorylase and the increase of haemolymph carbohydrates, which is dependent on the activation of glycogen phosphorylase in the model. It further explains the observed differences in sensitivity for glycogen phosphorylase activation and increase in haemolymph carbohydrates by these peptides. Best fits were obtained with a physiological half-life of about 12–15 min for the peptides. This value is similar to what can be calculated from the in vivo effects of these peptides on heart beat (Gersch et al., Zool. Jb. Physiol. 86, 17), but it is considerably shorter than the published half-life of 1 h for radioactive peptide (Skinner et al., Insect Biochem. 17, 433). However, both values are compatible if part of the peptides in the haemolymph is not present in freely dissolved form, but bound to a haemolymph component. The model half-life would then represent the half-life of the free, physiologically active peptide, which was estimated from the disappearance of radioactive peptide to be about 12–15 min. This suggests, that the model half-life is realistic and physiologically more important than the half-life of radioactive peptide of 1 h.

Abstract: Influence of the concentration of internal metabolites on the control coefficient (defined as fractional change in flux per fractional change in enzyme activity) and regulatory properties of a given enzyme have been studied theoretically using a cyclic model of three enzymes. This model is useful to investigate the properties of the flux control coefficient for an enzyme following different rate equations. Enzymes can have high or low values of control coefficient irrespective of the type of kinetic equation, but the results obtained show that the sensitivity of these values to substrate variations is strongly dependent on its rate equation. These results help identify which kinetic equation allows the best control of a given metabolic pathway. These results have been applied to the purine nucleotide cycle. It is demonstrated that the best control of the cycle is reached when the irreversible reaction catalyzed by AMP deaminase follows a rate law that corresponds to a rational function of 2 : 2 degree with respect to AMP concentration.

Abstract: In this paper the following problem is addressed: "Under what conditions can a collection of individual organisms learn to cooperate when cooperation appears to outwardly degrade individual performance at the outset. In order to attempt a theoretical solution to this problem, data from a real world problem in anthropology is used. A distributed simulation model of this system was developed to assess its long term behavior using using an approach suggested by Zeigler (Zeigler, B.P., 1984, Multifaceted Modelling and Discrete Event Simulation (Academic Press, London)). The results of the simulation are used to show that although cooperation degrades the performance potential of each individual, it enhances the persistence of the individual's partial solution to the problem in certain situations."

Abstract: A three-variable model of a continuous fermentation process characterised by product inhibition is studied. It is shown that if the cell to substrate yield is constant, the system cannot have periodic solutions. If, on the other hand, the yield term is a variable function of substrate concentration, the model will exhibit oscillations in the cells, substrate and product concentrations in the form of Hopf bifurcation in the underlying system of three nonlinear, ordinary differential equations which comprise the model.

Abstract: We use an excitable medium for dynamic pattern processing. For this purpose the autowave structures arising from the light-sensitive Belouzov-Zhabotinsky reaction could serve as attractors. The dynamics is simulated as a non-linear network with local interaction in terms of cellular automata. With the help of a set of threshold electrodes the actual state is projected into a space of bytes. At the end of the adaptation procedure for the parameters we achieved the ability of this system for pattern recognition. Dynamic and statis pattern processing are compared with respect to information capacity and adaption time.