Journal of theoretical Biology

Reply to the letter of Professors Brusch and Deutsch.

Publication Date: 2008 May 21 PMID: 18374952
Authors: Rothman, S.
Journal: J Theor Biol

post to: CiteULike

Is there a role for amplifiers in sexual selection?

Publication Date: 2008 May 21 PMID: 18371984
Authors: Gualla, F. - Cermelli, P. - Castellano, S.
Journal: J Theor Biol

The amplifier hypothesis states that selection could favour the evolution of traits in signallers that improve the ability of receivers to extract honest information from other signals or cues. We provide a formal definition of amplifiers based on the receiver's mechanisms of signal perception and we present a game-theoretical model in which males advertise their quality and females use sequential-sampling tactics to choose among prospective mates. The main effect of an amplifier on the female mating strategy is to increase her mating threshold, making the female more selective as the effectiveness of the amplifier increases. The effects of the amplifier on male advertising strategy depends both on the context and on the types of the amplifier involved. We consider two different contexts for the evolution of amplifiers (when the effect of amplifiers is on signals and when it is on cues) and two types of amplifiers (the 'neutral amplifier', when it improves quality assessment without altering male attractiveness, and the 'attractive amplifier', when it improves both quality assessment and male attractiveness). The game-theoretical model provides two main results. First, neutral and attractive amplifiers represent, respectively, a conditional and an unconditional signalling strategy. In fact, at the equilibrium, neutral amplifiers are displayed only by males whose advertising level lays above the female acceptance threshold, whereas attractive amplifiers are displayed by all signalling males, independent of their quality. Second, amplifiers of signals increase the differences in advertising levels between amplifying and not-amplifying males, but they decrease the differences within each group, so that the system converges towards an 'all-or-nothing' signalling strategy. By applying concepts from information theory, we show that the increase in information transfer at the perception level due to the amplifier of signals is contrasted by a decrease in information transfer at the emitter level due to the increased stereotypy of male advertising strategy.

post to: CiteULike

Optimal and suboptimal protocols for a class of mathematical models of tumor anti-angiogenesis.

Publication Date: 2008 May 21 PMID: 18371982
Authors: Ledzewicz, U. - Schattler, H.
Journal: J Theor Biol

Tumor anti-angiogenesis is a cancer treatment approach that aims at preventing the primary tumor from developing its own vascular network needed for further growth. In this paper the problem of how to schedule an a priori given amount of angiogenic inhibitors in order to minimize the tumor volume is considered for three related mathematical formulations of a biologically validated model developed by Hahnfeldt et al. [1999. Tumor development under angiogenic signalling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy. Cancer Res. 59, 4770-4775]. Easily implementable piecewise constant protocols are compared with the mathematically optimal solutions. It is shown that a constant dosage protocol with rate given by the averaged optimal control is an excellent suboptimal protocol for the original model that achieves tumor values that lie within 1% of the theoretically optimal values. It is also observed that the averaged optimal dose is decreasing as a function of the initial tumor volume.

post to: CiteULike

Reconstruction of certain phylogenetic networks from the genomes at their leaves.

Publication Date: 2008 May 21 PMID: 18367212
Authors: Willson, S. J.
Journal: J Theor Biol

A network N is a rooted acyclic digraph. A base-set X for N is a subset of vertices including the root (or outgroup), all leaves, and all vertices of outdegree 1. A simple model of evolution is considered in which all characters are binary and in which back-mutations occur only at hybrid vertices. It is assumed that the genome is known for each member of the base-set X. If the network is known and is assumed to be "normal," then it is proved that the genome of every vertex is uniquely determined and can be explicitly reconstructed. Under additional hypotheses involving time-consistency and separation of the hybrid vertices, the network itself can also be reconstructed from the genomes of all members of X. An explicit polynomial-time procedure is described for performing the reconstruction.

post to: CiteULike

The continuous public goods game and the evolution of cooperative sex ratios.

Publication Date: 2008 May 21 PMID: 18367211
Authors: Kamimura, Y. - Abe, J. - Ito, H.
Journal: J Theor Biol

Some animals, such as Melittobia wasps and surface-living mites, have extremely female-biased sex ratios that cannot be explained by the existing local mate competition (LMC) theories. The restricted production of sons may entail cooperation among mothers, enabling the production of more daughters and avoiding severe competition among sons for insemination access. These unusual examples are characterized by the long-term cohabitation of egg-layers (foundresses) on resource patches and possible contact with oviposited eggs. By applying the logic of mutual policing, we develop a novel game theoretical model for the evolution of cooperation in sex-ratio traits. This is the first attempt to model the evolution of sex ratios based on iterated games. We assumed that foundresses have two abilities to enable mutual policing: they can monitor the sex ratio in the resource patch, and they can punish defectors that produce an overabundance of males. Numerical analysis and evolutionary simulations demonstrate that cooperative low sex ratios can evolve when the number of foundresses per patch is sufficiently small. Our model predicts a slight, but steady increase in oviposition sex ratios with an increase in the number of foundresses, which mimics the phenomenon observed in several animals with extremely female-biased sex ratios. We also discuss the relationship between our model and other models of sex-ratio evolution.

post to: CiteULike

Thermodynamics of natural selection I: Energy flow and the limits on organization.

Publication Date: 2008 May 21 PMID: 18367210
Authors: Smith, E.
Journal: J Theor Biol

This is the first of three papers analyzing the representation of information in the biosphere, and the energetic constraints limiting the imposition or maintenance of that information. Biological information is inherently a chemical property, but is equally an aspect of control flow and a result of processes equivalent to computation. The current paper develops the constraints on a theory of biological information capable of incorporating these three characterizations and their quantitative consequences. The paper illustrates the need for a theory linking energy and information by considering the problem of existence and reslience of the biosphere, and presents empirical evidence from growth and development at the organismal level suggesting that the theory developed will capture relevant constraints on real systems. The main result of the paper is that the limits on the minimal energetic cost of information flow will be tractable and universal whereas the assembly of more literal process models into a system-level description often is not. The second paper in the series then goes on to construct reversible models of energy and information flow in chemistry which achieve the idealized limits, and the third paper relates these to fundamental operations of computation.

post to: CiteULike

Thermodynamics of natural selection II: Chemical Carnot cycles.

Publication Date: 2008 May 21 PMID: 18367209
Authors: Smith, E.
Journal: J Theor Biol

This is the second in a series of three papers devoted to energy flow and entropy changes in chemical and biological processes, and to their relations to the thermodynamics of computation. In the first paper of the series, it was shown that a general-form dimensional argument from the second law of thermodynamics captures a number of scaling relations governing growth and development across many domains of life. It was also argued that models of physiology based on reversible transformations provide sensible approximations within which the second-law scaling is realized. This paper provides a formal basis for decomposing general cyclic, fixed-temperature chemical reactions, in terms of the chemical equivalent of Carnot's cycle for heat engines. It is shown that the second law relates the minimal chemical work required to perform a cycle to the Kullback-Leibler divergence produced in its chemical output ensemble from that of a Gibbs equilibrium. Reversible models of physiology are used to create reversible models of natural selection, which relate metabolic energy requirements to information gain under optimal conditions. When dissipation is added to models of selection, the second-law constraint is generalized to a relation between metabolic work and the combined energies of growth and maintenance.

post to: CiteULike

The penguin waddling gait pattern has a more consistent step width than step length.

Publication Date: 2008 May 21 PMID: 18359044
Authors: Kurz, M. J. - Scott-Pandorf, M. - Arellano, C. - Olsen, D. - Whitaker, G.
Journal: J Theor Biol

Previous research has indicated that the sagittal plane gait dynamics of humans are more stable and less dependent on active neural control, while the frontal plane dynamics are less stable and require greater neural control. The higher neural demands of the frontal plane dynamics are reflected in a more variable step width than step length. Greater variability in the step width occurs because humans modulate their foot placement for each step to ensure stability and prevent falls. Compared to other terrestrial animals, penguins appear to have excessive amount of frontal plane motion in their gait that is characterized as waddling. If excessive frontal plane motion requires additional neural control and is associated with falls, it would seem that evolutionary pressures would have eliminated such locomotive strategies. Here we measured the step length and width variability to determine if waddling results in a less stable gait. Remarkably, the variability of the step width was less than the variability of the step length. These results are directly opposite of what has been reported for humans. Hence, our data indicate that waddling may be an effective strategy for ensuring stability in the frontal plane dynamics.

post to: CiteULike

Thermodynamics of natural selection III: Landauer's principle in computation and chemistry.

Publication Date: 2008 May 21 PMID: 18359043
Authors: Smith, E.
Journal: J Theor Biol

This is the third in a series of three papers devoted to energy flow and entropy changes in chemical and biological processes, and their relations to the thermodynamics of computation. The previous two papers have developed reversible chemical transformations as idealizations for studying physiology and natural selection, and derived bounds from the second law of thermodynamics, between information gain in an ensemble and the chemical work required to produce it. This paper concerns the explicit mapping of chemistry to computation, and particularly the Landauer decomposition of irreversible computations, in which reversible logical operations generating no heat are separated from heat-generating erasure steps which are logically irreversible but thermodynamically reversible. The Landauer arrangement of computation is shown to produce the same entropy-flow diagram as that of the chemical Carnot cycles used in the second paper of the series to idealize physiological cycles. The specific application of computation to data compression and error-correcting encoding also makes possible a Landauer analysis of the somewhat different problem of optimal molecular recognition, which has been considered as an information theory problem. It is shown here that bounds on maximum sequence discrimination from the enthalpy of complex formation, although derived from the same logical model as the Shannon theorem for channel capacity, arise from exactly the opposite model for erasure.

post to: CiteULike

Package models and the information crisis of prebiotic evolution.

Publication Date: 2008 May 21 PMID: 18358494
Authors: Silvestre, D. A. - Fontanari, J. F.
Journal: J Theor Biol

The coexistence between different types of templates has been the choice solution to the information crisis of prebiotic evolution, triggered by the finding that a single RNA-like template cannot carry enough information to code for any useful replicase. In principle, confining d distinct templates of length L in a package or protocell, whose survival depends on the coexistence of the templates it holds in, could resolve this crisis provided that d is made sufficiently large. Here we review the prototypical package model of Niesert et al. [1981. Origin of life between Scylla and Charybdis. J. Mol. Evol. 17, 348-353] which guarantees the greatest possible region of viability of the protocell population, and show that this model, and hence the entire package approach, does not resolve the information crisis. In particular, we show that the total information stored in a viable protocell (Ld) tends to a constant value that depends only on the spontaneous error rate per nucleotide of the template replication mechanism. As a result, an increase of d must be followed by a decrease of L, so that the net information gain is null.

post to: CiteULike

The effects of spatial inhomogeneities on flow through the endothelial surface layer.

Publication Date: 2008 May 21 PMID: 18358493
Authors: Leiderman, K. M. - Miller, L. A. - Fogelson, A. L.
Journal: J Theor Biol

Flow through the endothelial surface layer (the glycocalyx and adsorbed plasma proteins) plays an important but poorly understood role in cell signaling through a process known as mechanotransduction. Characterizing the flow rates and shear stresses throughout this layer is critical for understanding how flow-induced ionic currents, deformations of transmembrane proteins, and the convection of extracellular molecules signal biochemical events within the cell, including cytoskeletal rearrangements, gene activation, and the release of vasodilators. Previous mathematical models of flow through the endothelial surface layer are based upon the assumptions that the layer is of constant hydraulic permeability and constant height. These models also assume that the layer is continuous across the endothelium and that the layer extends into only a small portion of the vessel lumen. Results of these models predict that fluid shear stress is dissipated through the surface layer and is thus negligible near endothelial cell membranes. In this paper, such assumptions are removed, and the resultant flow rates and shear stresses through the layer are described. The endothelial surface layer is modeled as clumps of a Brinkman medium immersed in a Newtonian fluid. The width and spacing of each clump, hydraulic permeability, and fraction of the vessel lumen occupied by the layer are varied. The two-dimensional Navier-Stokes equations with an additional Brinkman resistance term are solved using a projection method. Several fluid shear stress transitions in which the stress at the membrane shifts from low to high values are described. These transitions could be significant to cell signaling since the endothelial surface layer is likely dynamic in its composition, density, and height.

post to: CiteULike

The modified Mahalanobis Discriminant for predicting outer membrane proteins by using Chou's pseudo amino acid composition.

Publication Date: 2008 May 21 PMID: 18355838
Authors: Lin, H.
Journal: J Theor Biol

The outer membrane proteins (OMPs) are beta-barrel membrane proteins that performed lots of biology functions. The discriminating OMPs from other non-OMPs is a very important task for understanding some biochemical process. In this study, a method that combines increment of diversity with modified Mahalanobis Discriminant, called IDQD, is presented to predict 208 OMPs, 206 transmembrane helical proteins (TMHPs) and 673 globular proteins (GPs) by using Chou's pseudo amino acid compositions as parameters. The overall accuracy of jackknife cross-validation is 93.2% and 96.1%, respectively, for three datasets (OMPs, TMHPs and GPs) and two datasets (OMPs and non-OMPs). These predicted results suggest that the method can be effectively applied to discriminate OMPs, TMHPs and GPs. And it also indicates that the pseudo amino acid composition can better reflect the core feature of membrane proteins than the classical amino acid composition.

post to: CiteULike

A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity.

Publication Date: 2008 May 21 PMID: 18353374
Authors: Isaksson, H. - van Donkelaar, C. C. - Huiskes, R. - Ito, K.
Journal: J Theor Biol

Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects of combined physical and biological interventions. In this study, a new model of cell and tissue differentiation, using a more mechanistic approach, is presented and applied to fracture repair. The model directly couples cellular mechanisms to mechanical stimulation during bone healing and is based on the belief that the cells act as transducers during tissue regeneration. In the model, the cells within the matrix proliferate, differentiate, migrate, and produce extracellular matrix, all at cell-phenotype specific rates, based on the mechanical stimulation they experience. The model is assembled from coupled partial differentiation equations, which are solved using a newly developed finite element formulation. The evolution of four cell types, i.e. mesenchymal stem cells, fibroblasts, chondrocytes and osteoblasts, and the production of extracellular matrices of fibrous tissue, cartilage and bone are calculated. The material properties of the tissues are iteratively updated based on actual amounts of extracellular matrix in material elements at progressive time points. A two-dimensional finite element model of a long bone osteotomy was used to evaluate the model's potential. The additional value of the presented model and the importance of including cell-phenotype specific activities when modeling tissue differentiation and bone healing, were demonstrated by comparing the predictions with phenomenological models. The model's capacity was established by showing that it can correctly predict several aspects of bone healing, including cell and tissue distributions during normal fracture healing. Furthermore, it was able to predict experimentally established alterations due to excessive mechanical stimulation, periosteal stripping and impaired effects of cartilage remodeling.

post to: CiteULike

Model of active transport of ions in cardiac cell.

Publication Date: 2008 May 21 PMID: 18353373
Authors: Melkikh, A. V. - Sutormina, M. I.
Journal: J Theor Biol

A model of the active transport of ions in a cardiac muscle cell, which takes into account the active transport of Na(+), K(+), Ca(2+), Mg(2+), HCO(3)(-) and Cl(-) ions, has been constructed. The model allows independent calculations of the resting potential at the biomembrane and concentrations of basic ions (sodium, potassium, chlorine, magnesium and calcium) in a cell. For the analysis of transport processes in cardiac cell hierarchical algorithm "one ion-one transport system" was offered. The dependence of the resting potential on concentrations of the ions outside a cell has been established. It was shown, that ions of calcium and magnesium, despite their rather small concentration, play an essential role in maintenance of resting potential in cardiac cell. The calculated internal concentrations of ions are in good agreement with the corresponding experimental values.

post to: CiteULike

Dynamical implications of Viral Tiling Theory.

Publication Date: 2008 May 21 PMID: 18353372
Authors: ElSawy, K. M. - Taormina, A. - Twarock, R. - Vaughan, L.
Journal: J Theor Biol

The Caspar-Klug classification of viruses whose protein shell, called viral capsid, exhibits icosahedral symmetry, has recently been extended to incorporate viruses whose capsid proteins are exclusively organised in pentamers. The approach, named 'Viral Tiling Theory', is inspired by the theory of quasicrystals, where aperiodic Penrose tilings enjoy 5-fold and 10-fold local symmetries. This paper analyses the extent to which this classification approach informs dynamical properties of the viral capsids, in particular the pattern of Raman active modes of vibrations, which can be observed experimentally.

post to: CiteULike

Relaxing the zero-sum assumption in neutral biodiversity theory.

Publication Date: 2008 May 21 PMID: 18346758
Authors: Haegeman, B. - Etienne, R. S.
Journal: J Theor Biol

The zero-sum assumption is one of the ingredients of the standard neutral model of biodiversity by Hubbell. It states that the community is saturated all the time, which in this model means that the total number of individuals in the community is constant over time, and therefore introduces a coupling between species abundances. It was shown recently that a neutral model with independent species, and thus without any coupling between species abundances, has the same sampling formula (given a fixed number of individuals in the sample) as the standard model [Etienne, R.S., Alonso, D., McKane, A.J., 2007. The zero-sum assumption in neutral biodiversity theory. J. Theor. Biol. 248, 522-536]. The equilibria of both models are therefore equivalent from a practical point of view. Here we show that this equivalence can be extended to a class of neutral models with density-dependence on the community-level. This result can be interpreted as robustness of the model, i.e. insensitivity of the model to the precise interaction of the species in a neutral community. It can also be interpreted as a lack of resolution, as different mechanisms of interactions between neutral species cannot be distinguished using only a single snapshot of species abundance data.

post to: CiteULike

Patch exploitation in two dimensions: from Daphnia to simulated foragers.

Publication Date: 2008 May 7 PMID: 18343411
Authors: Dees, N. D. - Bahar, S. - Garcia, R. - Moss, F.
Journal: J Theor Biol

We explore the variability that animals display in their movement choices as they forage in a finite-sized food patch with a uniform food distribution, and present a framework for how these choices may be adjusted to optimize foraging efficiency. Inspired by experimental studies of the zooplankton Daphnia, we model foraging animals as "agents" moving in two dimensions in repeated and successive sequences of hops, pauses, and turns. For Daphnia and other species, critical movement parameters such as hop lengths, pause times, and turning angles are typically reported as probability density functions. Similarly, the agents in our simulations choose their movement parameters at random from such distributions. Each distribution is defined by a characteristic width, which we interpret as a "noise width," available to be tuned for increased foraging efficiency. We investigate the sensitivity of the system by measuring the food gathered by the agents as the turning angle and hop length noise widths are varied. In all cases, we find a maximum in food gathered at some particular value of the noise width in question, suggesting that these results can be considered robust examples of natural stochastic resonance.

post to: CiteULike

Dynamics of sialyl Lewis(a) in aqueous solution and prediction of the structure of the sialyl Lewis(a)-SelectinE complex.

Publication Date: 2008 May 7 PMID: 18343410
Authors: Veluraja, K. - Seethalakshmi, A. N.
Journal: J Theor Biol

In this article we investigate all possible three-dimensional structures for sialyl Lewis(a) (SLe(a)) in aqueous solution and we predict without a priori experimental information its conformation when bound to SelectinE by using a combination of long molecular dynamics (MD) simulations. Based on 10ns MD studies, three structures differing in glycosidic conformations are proposed for SLe(a) in aqueous solution. Based on a 4ns MD study of the SLe(a)-SelectinE complex with initial structures derived from our prediction tools, we find that, fucose and N-acetyl neuraminic acid are in close contact with SelectinE and therefore expect interactions of the protein with these two sugar rings to be significantly more important than in the case of galactose and N-acetyl glucosamine. Our predictions indicate that the N-acetyl glucosamine of SLe(a) is positioned primarily in the aqueous phase. In order to be able to interact with SLe(a) the side chains of amino acid residues Lys99 and Lys111 in SelectinE appear to undergo large conformational changes when contrasted with the positions of these residues in the X-ray crystal structure. Furthermore, amino acid residues Arg97, Glu98 and Lys99 are acting as a holding arm to position the NeuNAc of SLe(a) in the binding pocket.

post to: CiteULike

Patterns of vegetation biodiversity: the roles of dispersal directionality and river network structure.

Publication Date: 2008 May 21 PMID: 18343409
Authors: Muneepeerakul, R. - Bertuzzo, E. - Rinaldo, A. - Rodriguez-Iturbe, I.
Journal: J Theor Biol

This paper investigates the importance of dispersal directionality and river network structure to biodiversity patterns. Our model results suggest that dispersal directionality plays a crucial role in determining biodiversity patterns, even more so than dispersal rates. Dispersal directionality heterogenizes the spatial distribution of abundance, which results in higher extinction rates of rare species and higher beta diversity. It induces a few species with very high abundances at the expense of many species with intermediate abundances, thereby lowering alpha and gamma diversities. The river network structure also increases beta diversity, i.e., more heterogeneous ecosystems, in comparison to typical two-dimensional landscapes. We find that the interplay between the dispersal directionality and network topology has important consequences on relative species abundance patterns and the distribution of alpha diversity.

post to: CiteULike

The influence of social structure on the propagation of social information in artificial primate groups: a graph-based simulation approach.

Publication Date: 2008 May 7 PMID: 18342891
Authors: Voelkl, B. - Noe, R.
Journal: J Theor Biol

Observations of primate groups have shown that social learning can lead to the development of temporal stable traditions or even proto-culture. The social structure of primate groups is highly diverse and it has been proposed that differences in the group structure shall influence the patterns of social information transmission. While empirical studies have mainly focused on the psychological mechanisms of social learning in individuals, the phenomenon of information propagation within the group has received relatively little attention. This might be due to the fact that formal theories that allow actual testing have not been formulated, or were kept too simple, ignoring the social dynamics of multi-agent societies. We want to propose a network approach to social information transmission that (1) preserves the complexity of the social structure of primate groups and (2) allows direct application to empirical data. Results from simulation experiments with artificial group structures confirm that association patterns of group-members influence the expected speed of information transmission during the propagation process. Introducing a forgetting rate shows that under certain conditions the proportion of informed individuals will reach a stable rate in some systems while it will drop to zero in others. This suggests that the likelihood to observe temporal stable traditions shall differ between social systems with different structure.

post to: CiteULike

Mutual interaction in network motifs robustly sharpens gene expression in developmental processes.

Publication Date: 2008 May 7 PMID: 18342890
Authors: Ishihara, S. - Shibata, T.
Journal: J Theor Biol

The gene regulatory network of a developmental process contains many mutually repressive interactions between two genes. They are often regulated by or regulate an additional factor, which constitute prominent network motifs, called regulated and regulating mutual loops. Our database analysis on the gene regulatory network for Drosophila melanogaster indicates that those with mutual repression are working specifically for the segmentation process. To clarify their biological roles, we mathematically study the response of the regulated mutual loop with mutual repression to input stimuli. We show that the mutual repression increases the response sensitivity without affecting the threshold input level to activate the target gene expression, as long as the network output is unique for a given input level. This high sensitivity of the motif can contribute to sharpening the spatial domain pattern without changing its position, assuring a robust developmental process. We also study transient dynamics that shows shift of domain boundary, agreeing with experimental observations. Importance of mutual repression is addressed by comparing with other types of regulations.

post to: CiteULike

Remote protein homology detection using recurrence quantification analysis and amino acid physicochemical properties.

Publication Date: 2008 May 7 PMID: 18342336
Authors: Yang, Y. - Tantoso, E. - Li, K. B.
Journal: J Theor Biol

Remote homology detection refers to the detection of structure homology in evolutionarily related proteins with low sequence similarity. Supervised learning algorithms such as support vector machine (SVM) are currently the most accurate methods. In most of these SVM-based methods, efforts have been dedicated to developing new kernels to better use the pairwise alignment scores or sequence profiles. Moreover, amino acids' physicochemical properties are not generally used in the feature representation of protein sequences. In this article, we present a remote homology detection method that incorporates two novel features: (1) a protein's primary sequence is represented using amino acid's physicochemical properties and (2) the similarity between two proteins is measured using recurrence quantification analysis (RQA). An optimization scheme was developed to select different amino acid indices (up to 10 for a protein family) that are best to characterize the given protein family. The selected amino acid indices may enable us to draw better biological explanation of the protein family classification problem than using other alignment-based methods. An SVM-based classifier will then work on the space described by the RQA metrics. The classification scheme is named as SVM-RQA. Experiments at the superfamily level of the SCOP1.53 dataset show that, without using alignment or sequence profile information, the features generated from amino acid indices are able to produce results that are comparable to those obtained by the published state-of-the-art SVM kernels. In the future, better prediction accuracies can be expected by combining the alignment-based features with our amino acids property-based features. Supplementary information including the raw dataset, the best-performing amino acid indices for each protein family and the computed RQA metrics for all protein sequences can be downloaded from http://ym151113.ym.edu.tw/svm-rqa.

post to: CiteULike

The coherence of the vesicle theory of protein secretion.

Publication Date: 2008 May 21 PMID: 18339405
Authors: Brusch, L. - Deutsch, A.
Journal: J Theor Biol

post to: CiteULike

Origins of the BOLD changes due to synaptic activity at astrocytes abutting arteriolar smooth muscle.

Publication Date: 2008 May 7 PMID: 18339404
Authors: Bennett, M. R. - Farnell, L. - Gibson, W. G.
Journal: J Theor Biol

We have recently provided a detailed model that links glutamatergic synaptic activity to volume and blood flow changes in nearby arterioles [Bennett, M.R., Farnell, L., Gibson, W.G., 2008. Origin of blood volume change due to glutamatergic synaptic activity at astrocytes abutting on arteriolar smooth muscle cells. J. Theor. Biol. 250, 172-185]. This neurovascular coupling model is used in the present work to predict changes in deoxyhemoglobin (Hbr) in capillaries, arterioles, venules and veins due to glutamatergic synaptic activity and hence the changes in the blood oxygen level dependent (BOLD) signals recorded by functional magnetic resonance imaging. The model provides a quantitative account of Hbr changes observed in each of the vascular compartments following stimulation of somatosensory cortex and visual cortex and of the BOLD signal following stimulation of motor and visual cortex.

post to: CiteULike

Cerebral perfusion pressure in giraffe: modelling the effects of head-raising and -lowering.

Publication Date: 2008 May 7 PMID: 18329049
Authors: Mitchell, G. - Bobbitt, J. P. - Devries, S.
Journal: J Theor Biol

Loss of consciousness caused by positional changes of the head results from reduced cerebral blood flow (CBF). CBF is related to cerebral perfusion pressure (CPP). CPP is the difference between mean arterial pressure (MAP) at the head and intracranial pressure (ICP). The positional change of the giraffe head between ground level and standing upright is the largest of all animals yet loss of consciousness does not occur. We have investigated the possibility that an increase in CPP protects giraffe from fainting, using a mechanical model that functioned as an anatomical U-tube. It consisted of a rigid ascending "carotid" limb, a collapsible "brain" tube drained by a rigid, "vertebral venous plexus" (VVP) tube, and a collapsible "head" tube drained by a collapsible tube representing the "jugular vein". The descending tubes could be rotated relative to the "carotid" tube to be horizontal, or at 30 degrees , 45 degrees , and 60 degrees to the vertical to simulate changes in head position. Pressure at the top of the "carotid" tube was intracranial MAP, at the top of the "VVP" tube was ICP, and the difference CPP. In the simulated "head-up" position and a fluid flow rate of 4 L min(-1), CPP was approximately 170 mmHg. With the VVP tube horizontal, CPP fell from approximately 170 to 45 mmHg, but increased to approximately 67 mmHg at 30 degrees "down", to approximately 70 mmHg at 45 degrees "down" and to approximately 75 at 60 degrees "down". The fall in CPP in the head-down positions resulted from a decrease in viscous resistance in, and dissipation of pressure to, the "head" and "jugular" tubes. These data provide an estimate of cranial pressure changes in giraffe during positional changes of the head, and suggest that an increase in CPP plays a significant role in maintaining CBF during head-raising and that it may be an important mechanism for preventing fainting in giraffe.

post to: CiteULike

Ecological balance in the native population dynamics may cause the paradox of pest control with harvesting.

Publication Date: 2008 May 7 PMID: 18329048
Authors: Matsuoka, T. - Seno, H.
Journal: J Theor Biol

We analyze a time-discrete mathematical model of host-parasite population dynamics with harvesting, in which the host can be regarded as a pest. We harvest a portion of the host population at a moment in each parasitism season. The principal target of the harvesting is the host; however, the parasite population may also be affected and reduced by a portion. Our model involves the Beverton-Holt type density effect on the host population. We investigate the condition in which the harvesting of the host results in an eventual increase of its equilibrium population size, analytically proving that the paradoxical increase could occur even when the harvesting does not directly affect the parasite population at all. We show that the paradox of pest control could be caused essentially by the interspecific relationship and the intraspecific density effect.

post to: CiteULike

Analysis and IbM simulation of the stages in bacterial lag phase: basis for an updated definition.

Publication Date: 2008 May 7 PMID: 18329047
Authors: Prats, C. - Giro, A. - Ferrer, J. - Lopez, D. - Vives-Rego, J.
Journal: J Theor Biol

The lag phase is the initial phase of a culture that precedes exponential growth and occurs when the conditions of the culture medium differ from the pre-inoculation conditions. It is usually defined by means of cell density because the number of individuals remains approximately constant or slowly increases, and it is quantified with the lag parameter lambda. The lag phase has been studied through mathematical modelling and by means of specific experiments. In recent years, Individual-based Modelling (IbM) has provided helpful insights into lag phase studies. In this paper, the definition of lag phase is thoroughly examined. Evolution of the total biomass and the total number of bacteria during lag phase is tackled separately. The lag phase lasts until the culture reaches a maximum growth rate both in biomass and cell density. Once in the exponential phase, both rates are constant over time and equal to each other. Both evolutions are split into an initial phase and a transition phase, according to their growth rates. A population-level mathematical model is presented to describe the transitional phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check the outcomes of this analysis. Simulations allow the separate study of the evolution of cell density and total biomass in a batch culture, they provide a depiction of different observed cases in lag evolution at the individual-cell level, and are used to test the population-level model. The results show that the geometrical lag parameter lambda is not appropriate as a universal definition for the lag phase. Moreover, the lag phase cannot be characterized by a single parameter. For the studied cases, the lag phases of both the total biomass and the population are required to fully characterize the evolution of bacterial cultures. The results presented prove once more that the lag phase is a complex process that requires a more complete definition. This will be possible only after the phenomena governing the population dynamics at an individual level of description, and occurring during the lag and exponential growth phases, are well understood.

post to: CiteULike

Backward bifurcations and multiple equilibria in epidemic models with structured immunity.

Publication Date: 2008 May 7 PMID: 18325538
Authors: Reluga, T. C. - Medlock, J. - Perelson, A. S.
Journal: J Theor Biol

Many disease pathogens stimulate immunity in their hosts, which then wanes over time. To better understand the impact of this immunity on epidemiological dynamics, we propose an epidemic model structured according to immunity level that can be applied in many different settings. Under biologically realistic hypotheses, we find that immunity alone never creates a backward bifurcation of the disease-free steady state. This does not rule out the possibility of multiple stable equilibria, but we provide two sufficient conditions for the uniqueness of the endemic equilibrium, and show that these conditions ensure uniqueness in several common special cases. Our results indicate that the within-host dynamics of immunity can, in principle, have important consequences for population-level dynamics, but also suggest that this would require strong non-monotone effects in the immune response to infection. Neutralizing antibody titer data for measles are used to demonstrate the biological application of our theory.

post to: CiteULike

Is convergence surprising? An examination of the frequency of convergence in simulated datasets.

Publication Date: 2008 May 7 PMID: 18321532
Authors: Stayton, C. T.
Journal: J Theor Biol

Although convergence is recognized as a central concept in evolutionary biology, very few tools are available for the quantitative study of this phenomenon. Moreover, although many evolutionary assertions assume that convergence should be rare in the absence of influences on organismal phenotypes such as natural selection or constraint, no studies have tested whether this is the case. I simulate random evolution (Brownian motion model) of quantitative characters along phylogenies with varying numbers of terminal taxa, numbers of traits, variance structure, and tree balance, and quantify the amount of convergence observed in these datasets using four metrics. The amount of convergence observed in a dataset increases with increasing number of taxa and decreasing number of traits, approaching the maximum possible amount of convergence under certain circumstances. Some convergence is expected in almost all datasets. Comparison of empirical datasets to those produced by random evolution provides a test of whether empirical datasets actually show elevated levels of convergence. Out of three test datasets, two show more convergence than expected. Given that high levels of convergence can be produced simply by random evolution, no explanation may be necessary for instances of convergence discovered in an evolutionary investigation.

post to: CiteULike

The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection.

Publication Date: 2008 May 7 PMID: 18321531
Authors: Ray, J. C. - Wang, J. - Chan, J. - Kirschner, D. E.
Journal: J Theor Biol

During most infections, the population of immune cells known as macrophages are key to taking up and killing bacteria as an integral part of the immune response. However, during infection with Mycobacterium tuberculosis (Mtb), host macrophages serve as the preferred environment for mycobacterial growth. Further, killing of Mtb by macrophages is impaired unless they become activated. Activation is induced by stimulation from bacterial antigens and inflammatory cytokines derived from helper T cells. The key macrophage-activating cytokines in Mtb infection are tumor necrosis factor-alpha (TNF) and interferon (IFN)-gamma. Due to differences in cellular sources and secretion pathways for TNF and IFN-gamma, the possibility of heterogeneous cytokine distributions exists, suggesting that the timing of macrophage activation from these signals may affect activation kinetics and thus impact the outcome of Mtb infection. Here we use a mathematical model to show that negative feedback from production of nitric oxide (the key mediator of mycobacterial killing) that typically optimizes macrophage responses to activating stimuli may reduce effective killing of Mtb. Statistical sensitivity analysis predicts that if TNF and IFN-gamma signals precede infection, the level of negative feedback may have a strong effect on how effectively macrophages kill Mtb. However, this effect is relaxed when IFN-gamma or TNF+IFN-gamma signals are received coincident with infection. Under these conditions, the model suggests that negative feedback induces fast responses and an initial overshoot of nitric oxide production for given doses of TNF and IFN-gamma, favoring killing of Mtb. Together, our results suggest that direct entry of macrophages into a granuloma site (and not distal to it) from lung vascular sources represents a preferred host strategy for mycobacterial control. We examine implications of these results in establishment of latent Mtb infection.

post to: CiteULike

The influence of turning angles on the success of non-oriented animal searches.

Publication Date: 2008 May 7 PMID: 18321530
Authors: Bartumeus, F. - Catalan, J. - Viswanathan, G. M. - Raposo, E. P. - da Luz, M. G.
Journal: J Theor Biol

Animal searches cover a full range of possibilities from highly deterministic to apparently completely random behaviors. However, even those stochastic components of animal movement can be adaptive, since not all random distributions lead to similar success in finding targets. Here we address the general problem of optimizing encounter rates in non-deterministic, non-oriented searches, both in homogeneous and patchy target landscapes. Specifically, we investigate how two different features related to turning angle distributions influence encounter success: (i) the shape (relative kurtosis) of the angular distribution and (ii) the correlations between successive relative orientations (directional memory). Such influence is analyzed in correlated random walk models using a proper choice of representative turning angle distributions of the recently proposed Jones and Pewsey class. We consider the cases of distributions with nearly the same shape but considerably distinct correlation lengths, and distributions with same correlation but with contrasting relative kurtosis. In homogeneous landscapes, we find that the correlation length has a large influence in the search efficiency. Moreover, similar search efficiencies can be reached by means of distinctly shaped turning angle distributions, provided that the resulting correlation length is the same. In contrast, in patchy landscapes the particular shape of the distribution also becomes relevant for the search efficiency, specially at high target densities. Excessively sharp distributions generate very inefficient searches in landscapes where local target density fluctuations are large. These results are of evolutionary interest. On the one hand, it is shown that equally successful directional memory can arise from contrasting turning behaviors, therefore increasing the likelihood of robust adaptive stochastic behavior. On the other hand, when target landscape is patchy, adequate tumbling may help to explore better local scale heterogeneities, being some details of the shape of the distribution also potentially adaptive.

post to: CiteULike

Modeling of cancer virotherapy with recombinant measles viruses.

Publication Date: 2008 May 7 PMID: 18316099
Authors: Bajzer, Z. - Carr, T. - Josic, K. - Russell, S. J. - Dingli, D.
Journal: J Theor Biol

The Edmonston vaccine strain of measles virus has potent and selective activity against a wide range of tumors. Tumor cells infected by this virus or genetically modified strains express viral proteins that allow them to fuse with neighboring cells to form syncytia that ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. We present a model of tumor and virus interactions based on established biology and with proper accounting of the free virus population. The range of model parameters is estimated by fitting to available experimental data. The stability of equilibrium states corresponding to complete tumor eradication, therapy failure and partial tumor reduction is discussed. We use numerical simulations to explore conditions for which the model predicts successful therapy and tumor eradication. The model exhibits damped, as well as stable oscillations in a range of parameter values. These oscillatory states are organized by a Hopf bifurcation.

post to: CiteULike

A metabolic view of the diversity-stability relationship.

Publication Date: 2008 May 7 PMID: 18316098
Authors: Lopez-Villalta, J. S.
Journal: J Theor Biol

A theoretical analysis of the "portfolio effect" expressed in metabolic terms indicates that the coefficient of variation of total biomass in the ecosystem is influenced by three factors: metabolic diversity, total population size and organism biomass (body mass). The contribution of these factors to ecosystem stability depends on the power scaling of population size to its temporal variance: the Tilman's z. In natural populations, 1 < z < 2 both from a theoretical and an empirical background, and so a higher metabolic diversity, a larger population size and a bigger body mass are expected to increase ecosystem stability. The maximization of any of these factors will enhance ecosystem stability both at ecological (successional) and evolutionary timescales, which could explain a number of trends observed in ecosystems and in the history of life.

post to: CiteULike

Abundance patterns in multi-species communities exposed to habitat destruction.

Publication Date: 2008 Apr 21 PMID: 18313697
Authors: Morozov, A. - Li, B. L.
Journal: J Theor Biol

Habitat destruction resulting from human activity is a serious threat to biodiversity. The model developed by Tilman et al. [Tilman, D., May, R.M., Lehman, C.L., Nowak, M.A., 1994. Habitat destruction and the extinction debt. Nature 371, 65-66] has become an important tool for analyzing persistence of species in habitats under destruction. However, most analysis and applications of this model have been limited to the studies of species richness and the order of extinction. In this paper, we address other important issues related to succession of species abundances. We are interested in how the abundance ranking (i.e., the ranking of species according to their relative abundances), the rank-abundance curve and the community diversity alter in habitats under destruction. We treat analytically the model of Tilman et al. and investigate three different scenarios. We consider that before destruction: (i) best competitors are most abundant; (ii) all species are equally abundant; (iii) poor competitors are most abundant. In each case, we have derived explicit expressions for equilibrium species abundances depending on proportion of destroyed sites. Then we follow analytically alteration in the initial abundance ranking, show complex patterns of succession of species abundances and consider transformations in the rank-abundance curve. We demonstrate patterns of self-organization in abundance distributions emerging as a response to habitat destruction. We show non-monotonic dependence of community diversity and community evenness on proportion of destroyed sites.

MeSH Categories: Animals, *Biodiversity, Competitive Behavior, Conservation of Natural Resources, *Ecosystem, Extinction, Biological, Food Chain, Models, Biological, *Population Density

post to: CiteULike

Evolutionarily distinctive species often capture more phylogenetic diversity than expected.

Publication Date: 2008 Apr 21 PMID: 18313078
Authors: Redding, D. W. - Hartmann, K. - Mimoto, A. - Bokal, D. - Devos, M. - Mooers, A. O.
Journal: J Theor Biol

Evolutionary distinctiveness measures of how evolutionarily isolated a species is relative to other members of its clade. Recently, distinctiveness metrics that explicitly incorporate time have been proposed for conservation prioritization. However, we found that such measures differ qualitatively in how well they capture the total amount of evolution (termed phylogenetic diversity, or PD) represented by a set of species. We used simulation and simple graph theory to explore this relationship with reference to phylogenetic tree shape. Overall, the distinctiveness measures capture more PD on more unbalanced trees and on trees with many splits near the present. The rank order of performance was robust across tree shapes, with apportioning measures performing best and node-based measures performing worst. A sample of 50 ultrametric trees from the literature showed the same patterns. Taken together, this suggests that distinctiveness metrics may be a useful addition to other measures of value for conservation prioritization of species. The simplest measure, the age of a species, performed surprisingly well, suggesting that new measures that focus on tree shape near the tips may provide a transparent alternative to more complicated full-tree approaches.

MeSH Categories: Animals, *Biodiversity, *Computer Simulation, *Evolution, *Models, Genetic, Phylogeny, Selection (Genetics)

post to: CiteULike

From individual behaviour to population models: a case study using swimming algae.

Publication Date: 2008 Apr 21 PMID: 18313077
Authors: Bearon, R. N. - Grunbaum, D.
Journal: J Theor Biol

Trajectories of swimming algae are analysed, and two random-walk models developed to link the individual-level behaviour of cells to population-level advection-diffusion models for the spatial-temporal distribution of cells. The models are both of the advection-diffusion form but are based on two different sets of assumptions about the underlying random-walk behaviours, a velocity jump behaviour and a velocity diffusion behaviour. The mathematical models were developed to allow for an arbitrary (non-weak) bias in the random walk and a variable swimming speed in order to represent the experimental data. For the algal species considered, Heterosigma akashiwo, the mean upward swimming speed was computed as 40 microm s(-1), and the calculated diffusion constants ranged from 2 x 10(3) to 4 x 10(4) microm(2) s(-1) depending on the details of the models. That two widely used modelling approaches yield substantially different population-level predictions when applied to the same empirical data suggests that better theoretical tools are needed for identifying adequate approximations for behavioural characteristics.

MeSH Categories: Algae/physiology, *Computer Simulation, *Ecosystem, Models, Biological, *Models, Statistical, *Movement, Swimming

post to: CiteULike

Diverse metabolic model parameters generate similar methionine cycle dynamics.

Publication Date: 2008 Apr 21 PMID: 18313076
Authors: Piazza, M. - Feng, X. J. - Rabinowitz, J. D. - Rabitz, H.
Journal: J Theor Biol

Parameter estimation constitutes a major challenge in dynamic modeling of metabolic networks. Here we examine, via computational simulations, the influence of system nonlinearity and the nature of available data on the distribution and predictive capability of identified model parameters. Simulated methionine cycle metabolite concentration data (both with and without corresponding flux data) was inverted to identify model parameters consistent with it. Thousands of diverse parameter families were found to be consistent with the data to within moderate error, with most of the parameter values spanning over 1000-fold ranges irrespective of whether flux data was included. Due to strong correlations within the extracted parameter families, model predictions were generally reliable despite the broad ranges found for individual parameters. Inclusion of flux data, by strengthening these correlations, resulted in substantially more reliable flux predictions. These findings suggest that, despite the difficulty of extracting biochemically accurate model parameters from system level data, such data may nevertheless prove adequate for driving the development of predictive dynamic metabolic models.

MeSH Categories: Animals, *Computer Simulation, Enzymes/metabolism, Homeostasis, *Metabolic Networks and Pathways, Methionine/*metabolism, Models, Biological, Systems Biology

post to: CiteULike

Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension.

Publication Date: 2008 Apr 21 PMID: 18304583
Authors: Sudar, E. - Velebit, J. - Gluvic, Z. - Zakula, Z. - Lazic, E. - Vuksanovic-Topic, L. - Putnikovic, B. - Neskovic, A. - Isenovic, E. R.
Journal: J Theor Biol

Causal relationship between sodium and hypertension has been proposed and various changes in Na+,K+-ATPase (sodium pump) activity have been described in established primary hypertension. A number of direct vascular effects of estradiol have been reported, including its impact on the regulation of sodium pump activity and vasomotor tone. The effects of estradiol involve the activation of multiple signaling cascades, including phosphatydil inositol-3 kinase (PI3K) and p42/44 mitogen-activated protein kinase (p42/44(MAPK)). In addition, some of the effects of estradiol have been linked to activity of cytosolic phospholipase A(2) (cPLA(2)). One possible cardioprotective mechanism of estradiol involves of the interaction between estradiol and the rennin-angiotensin system (RAS). Elevated circulating and tissue levels of angiotensin II (Ang II) have been implicated in the development of hypertension and heart failure. The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump, in vascular smooth muscle cells (VSMC). The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump activity/expression in VSMC, with particular emphasis on PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. Our primary hypothesis is that estradiol stimulates sodium pump activity/expression in VSMC via PI3K/cPLA(2)/p42/44(MAPK) dependent mechanism and, that impaired estradiol-stimulated sodium pump activity/expression in hypertensive rodent models (i.e. SHR), Ang II-mediated vascular impairment of estradiol is related to a decrease ability of estradiol to stimulate the PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. An important corollary to this hypothesis is that in hypertensive state (i.e. SHR rats) the decreasing in ACE enzyme activity and/or AT1 receptor expression caused by administration of estradiol is accompanying with abrogated ability of Ang II to decrease IRS-1/PI3K association, and consequent PI3K/cPLA(2)/p42/44(MAPK) activity and associated sodium pump activity/expression. A clear characterization of how Ang II attenuates estradiol signaling may lead to a better understanding of the molecular mechanism(s) underlying pathophysiological conditions such as hypertension and to understanding how certain pathophysiological situations affect sodium pump activity/expression in VSMC.

MeSH Categories: 1-Phosphatidylinositol 3-Kinase/metabolism, Angiotensin II/metabolism, Animals, Aorta, Cells, Cultured, Estradiol/*physiology, Humans, Hypertension/*metabolism, Male, Mitogen-Activated Protein Kinases/metabolism, *Models, Cardiovascular, Myocytes, Smooth Muscle/*metabolism, Rats, Rats, Wistar, Renin-Angiotensin System/physiology, Sodium-Potassium-Exchanging ATPase/*metabolism

post to: CiteULike

Evolutionary stability on graphs.

Publication Date: 2008 Apr 21 PMID: 18295801
Authors: Ohtsuki, H. - Nowak, M. A.
Journal: J Theor Biol

Evolutionary stability is a fundamental concept in evolutionary game theory. A strategy is called an evolutionarily stable strategy (ESS), if its monomorphic population rejects the invasion of any other mutant strategy. Recent studies have revealed that population structure can considerably affect evolutionary dynamics. Here we derive the conditions of evolutionary stability for games on graphs. We obtain analytical conditions for regular graphs of degree k > 2. Those theoretical predictions are compared with computer simulations for random regular graphs and for lattices. We study three different update rules: birth-death (BD), death-birth (DB), and imitation (IM) updating. Evolutionary stability on sparse graphs does not imply evolutionary stability in a well-mixed population, nor vice versa. We provide a geometrical interpretation of the ESS condition on graphs.

MeSH Categories: Animals, *Computer Simulation, *Evolution, *Game Theory, Genetic Drift, *Population Dynamics

post to: CiteULike

Song learning as an indicator mechanism: modelling the developmental stress hypothesis.

Publication Date: 2008 Apr 21 PMID: 18294656
Authors: Ritchie, G. R. - Kirby, S. - Hawkey, D. J.
Journal: J Theor Biol

The 'developmental stress hypothesis' attempts to provide a functional explanation of the evolutionary maintenance of song learning in songbirds. It argues that song learning can be viewed as an indicator mechanism that allows females to use learned features of song as a window on a male's early development, a potentially stressful period that may have long-term phenotypic effects. In this paper we formally model this hypothesis for the first time, presenting a population genetic model that takes into account both the evolution of genetic learning preferences and cultural transmission of song. The models demonstrate that a preference for song types that reveal developmental stress can evolve in a population, and that cultural transmission of these song types can be stable, lending more support to the hypothesis.

MeSH Categories: Animals, *Critical Period (Psychology), Evolution, Female, Genetics, Population, Learning/*physiology, Male, *Models, Genetic, Sexual Behavior, Animal, Songbirds/genetics/*growth & development, *Stress, Vocalization, Animal/*physiology

post to: CiteULike

Cost and complexity: selection for speech and language.

Publication Date: 2008 Apr 21 PMID: 18291421
Authors: Locke, J. L.
Journal: J Theor Biol

The handicap principle has been applied to a number of different traits in the last three decades, but it is difficult to characterize its record, or even its perceived relevance, when it comes to an important human attribute-spoken language. In some cases, assumptions regarding the energetic cost of speech, and the veracity of linguistically encoded messages, have failed to recognize critical aspects of human development, cognition, and social ecology. In other cases, the fact that speech contains honest (physiological) information, and tends to be used honestly with family and friends, has been overlooked. Speech and language are functionally related but they involve different resources. Individuals can increase the attractiveness of their speech, and of more stylized vocal and verbal performances, without enhancing linguistic structure or content; and they can modify their use of language without significant changes in the physical form of speech. That its production costs are normally low enables speech to be produced extravagantly in bids for status and mating relationships, and in evolution, may have allowed its content--linguistic knowledge and structure--to become complex.

MeSH Categories: Cognition, Communication, Humans, *Language, *Selection (Genetics), Social Environment, Speech/*physiology, Verbal Behavior

post to: CiteULike

Diffusion-limited reactions in G-protein activation: unexpected consequences of antagonist and agonist competition.

Publication Date: 2008 Apr 21 PMID: 18289560
Authors: Brinkerhoff, C. J. - Choi, J. S. - Linderman, J. J.
Journal: J Theor Biol

In this work, we ask whether the simultaneous movement of agonist and antagonist among surface receptors (i.e. continually associating and dissociating from individual receptors according to specified kinetics) has any unexpected consequences for G-protein activation and receptor desensitization. A Monte Carlo model framework is used to track the diffusion and reaction of individual receptors, allowing the requirement for receptors and G-proteins or receptors and kinases to find each other by diffusion (collision coupling) to be implemented explicitly. We find that at constant agonist occupancy the effect of an antagonist on both G-protein activation and the ratio of G-protein activation to receptor desensitization can be modulated by varying the antagonist dissociation kinetics. The explanation for this effect is that antagonist dissociation kinetics influence the ability of agonists to access particular receptors and thus reach G-proteins and kinases near those receptors. Relevant parameter ranges for observation of these effects are identified. These results are useful for understanding experimental and therapeutic situations when both agonist and antagonist are present, and in addition may offer new insights into insurmountable antagonism.

MeSH Categories: Animals, Cell Membrane/*metabolism, *Computer Simulation, Diffusion, GTP-Binding Proteins/agonists/antagonists & inhibitors/*metabolism, Humans, Models, Biological, Monte Carlo Method, Phosphorylation, Phosphotransferases/metabolism, Protein Binding, Receptors, Cell Surface/*metabolism, Signal Transduction/*physiology

post to: CiteULike

Adaptation to slow environmental change, with apparent anticipation of selection.

Publication Date: 2008 May 7 PMID: 18289559
Authors: Sato, M. - Waxman, D.
Journal: J Theor Biol

We investigate a genetic model of a large population of sexual organisms in a changing environment. The organisms are subject to stabilising selection on a quantitative trait, with environmental change causing the fitness optimum to move. When the fitness optimum moves slowly, adaptation to the changing environment occurs by means of reasonably well-separated substitutions at the loci controlling the trait. In this way, the trait generally tracks the moving optimum, but in such a case, the population may exhibit periods of time where the mean trait value overshoots the moving optimal trait value, thereby exhibiting an apparent anticipation of selection. The mechanism underlying this phenomenon is determined from consideration of a simpler model that correctly captures the observed dynamical behaviour. We note that very slow rates of changes of traits are seen in the fossil record and the present work may be relevant to this topic.

post to: CiteULike

Stochastic simulation of actin dynamics reveals the role of annealing and fragmentation.

Publication Date: 2008 May 7 PMID: 18279896
Authors: Fass, J. - Pak, C. - Bamburg, J. - Mogilner, A.
Journal: J Theor Biol

Recent observations of F-actin dynamics call for theoretical models to interpret and understand the quantitative data. A number of existing models rely on simplifications and do not take into account F-actin fragmentation and annealing. We use Gillespie's algorithm for stochastic simulations of the F-actin dynamics including fragmentation and annealing. The simulations vividly illustrate that fragmentation and annealing have little influence on the shape of the polymerization curve and on nucleotide profiles within filaments but drastically affect the F-actin length distribution, making it exponential. We find that recent surprising measurements of high length diffusivity at the critical concentration cannot be explained by fragmentation and annealing events unless both fragmentation rates and frequency of undetected fragmentation and annealing events are greater than previously thought. The simulations compare well with experimentally measured actin polymerization data and lend additional support to a number of existing theoretical models.

post to: CiteULike

A mathematical model of spontaneous calcium(II) oscillations in astrocytes.

Publication Date: 2008 Apr 21 PMID: 18275973
Authors: Lavrentovich, M. - Hemkin, S.
Journal: J Theor Biol

Astrocytes exhibit oscillations and waves of Ca2+ ions within their cytosol and it appears that this behavior helps facilitate the astrocyte's interaction with its environment, including its neighboring neurons. Often changes in the oscillatory behavior are initiated by an external stimulus such as glutamate, recently however, it has been observed that oscillations are also initiated spontaneously. We propose here a mathematical model of how spontaneous Ca2+ oscillations arise in astrocytes. This model uses the calcium-induced calcium release and inositol cross-coupling mechanisms coupled with a receptor-independent method for producing inositol (1,4,5)-trisphosphate as the heart of the model. By computationally mimicking experimental constraints we have found that this model provides results that are qualitatively similar to experiment.

MeSH Categories: Animals, Astrocytes/*metabolism, Calcium/*metabolism, Calcium Channels/metabolism, Calcium Signaling, Cytosol/*metabolism, Endoplasmic Reticulum/metabolism, Humans, Inositol 1,4,5-Trisphosphate/metabolism, Inositol 1,4,5-Trisphosphate Receptors/metabolism, Models, Biological, Neurons/metabolism

post to: CiteULike

Environmental regulation can arise under minimal assumptions.

Publication Date: 2008 Apr 21 PMID: 18262569
Authors: McDonald-Gibson, J. - Dyke, J. G. - Di Paolo, E. A. - Harvey, I. R.
Journal: J Theor Biol

Models that demonstrate environmental regulation as a consequence of organism and environment coupling all require a number of core assumptions. Many previous models, such as Daisyworld, require that certain environment-altering traits have a selective advantage when those traits also contribute towards global regulation. We present a model that results in the regulation of a global environmental resource through niche construction without employing this and other common assumptions. There is no predetermined environmental optimum towards which regulation should proceed assumed or coded into the model. Nevertheless, polymorphic stable states that resist perturbation emerge from the simulated co-evolution of organisms and environment. In any single simulation a series of different stable states are realised, punctuated by rapid transitions. Regulation is achieved through two main subpopulations that are adapted to slightly different resource values, which force the environmental resource in opposing directions. This maintains the resource within a comparatively narrow band over a wide range of external perturbations. Population driven oscillations in the resource appear to be instrumental in protecting the regulation against mutations that would otherwise destroy it. Sensitivity analysis shows that the regulation is robust to mutation and to a wide range of parameter settings. Given the minimal assumptions employed, the results could reveal a mechanism capable of environmental regulation through the by-products of organisms.

MeSH Categories: Adaptation, Physiological, Animals, *Computer Simulation, *Ecology, *Environment, *Evolution, Humans, Models, Biological, Population Dynamics, Selection (Genetics)

post to: CiteULike

Calculating independent contrasts for the comparative study of substitution rates.

Publication Date: 2008 Apr 21 PMID: 18249413
Authors: Welch, J. J. - Waxman, D.
Journal: J Theor Biol

Phylogenetic comparative methods have been used to study patterns of correlated evolution between biological traits of all kinds, and are increasingly used to identify predictors of the rate of DNA substitution. Substitution rate differs from most traits studied in that it cannot be observed directly, but must be inferred from substitutions accrued over a long period of time. Studying a mathematical model of trait and rate evolution, we show that the special nature of substitution rates can lead to a severe loss of power for standard comparative methods. We further show how strategies designed to maximise power, by increasing the number of data points, can have the opposite effect when substitution rate is involved. We then propose two modifications of the standard methods that can mitigate these problems. First, we show how pre-existing tests for homogeneity of variance can be used to identify and exclude those data from which changes in substitution rate cannot be reliably inferred. Second, we show that power can be increased by comparing substitution rate with the time average of the predictor trait along the history of the lineage, and introduce a maximum likelihood estimator of this quantity.

MeSH Categories: Animals, Evolution, *Evolution, Molecular, *Models, Genetic, *Models, Statistical, Mutation, *Phylogeny, Quantitative Trait, Heritable

post to: CiteULike

The tri-frame model.

Publication Date: 2008 Apr 21 PMID: 18237749
Authors: Pienaar, E. - Viljoen, H. J.
Journal: J Theor Biol

The tri-frame model gives mathematical expression to the transcription and translation processes, and considers all three reading frames (RFs). RNA polymerases transcribe DNA in single nucleotide increments, but ribosomes translate mRNA in pairings of three (triplets or codons). The set of triplets in the mRNA, starting with the initiation codon (usually AUG) defines the open reading frame (ORF). Since ribosomes do not always translocate three nucleotide positions, two additional RFs are accessible. The -1 RF and the +1 RF are triplet pairings of the mRNA, which are accessed by shifting one nucleotide position in the 5' and 3' directions, respectively. Transcription is modeled as a linear operator that maps the initial codons in all three frames into other codon sets to account for possible transcriptional errors. Translational errors (missense errors) originate from misacylation of tRNAs and misreading of aa-tRNAs by the ribosome. Translation is modeled as a linear mapping from codons into aa-tRNA species, which includes misreading errors. A final transformation from aa-tRNA species into amino acids provides the probability distributions of possible amino acids into which the codons in all three frames could be translated. An important element of the tri-frame model is the ribosomal occupancy probability. It is a vector in R(3) that gives the probability to find the ribosome in the ORF, -1 or +1 RF at each codon position. The sequence of vectors, from the first to the final codon position, gives a history of ribosome frameshifting. The model is powerful: it provides explicit expressions for (1) yield of error-free protein, (2) fraction of prematurely terminated polypeptides, (3) number of transcription errors, (4) number of translation errors and (5) mutations due to frameshifting. The theory is demonstrated for the three genes rpsU, dnaG and rpoD of Escherichia coli, which lie on the same operon, as well as for the prfB gene.

MeSH Categories: Amino Acids/genetics, Animals, Frameshift Mutation, Humans, *Models, Genetic, *Open Reading Frames, Protein Biosynthesis, Transcription, Genetic

post to: CiteULike