Morse potential in DNA molecule – An experiment proposal

We rely on the helicoidal Peyrard-Bishop model for DNA dynamics. Interaction between nucleotides at a same site belonging to different strands is modelled by a Morse potential energy. This potential depends on two parameters that are different for AT and CG pairs, which is a possible source for inhomogeneity. It was shown recently (Zdravkovic and Sataric 2011) that certain values of these parameters bring about a negligible influence of inhomogeneity on the solitonic dynamics. We propose an experiment that should be carried out in order to determine the values of both of these parameters.     

Functional impacts of non-synonymous single nucleotide polymorphisms: selective constraint and structural environments

In this work, we studied the correlations between selective constraint, structural environments and functional impacts of non-synonymous single nucleotide polymorphisms (nsSNPs). We found that the relation between solvent accessibility and functional impacts of nsSNPs is not as simple as generally thought. Finer structural classifications need to be taken into account to reveal the complex relations between the characteristics of a structure environment and its influence on the functional impacts of nsSNPs. We introduced two parameters for each structural environment, consensus residue percentage and residue distribution distance, to characterize the selective constraint imposed by the environment. Both parameters significantly correlate with the functional bias of nsSNPs across the structural environments. This result shows that selective constraint underlies the bias of a structural environment towards a certain type of nsSNPs (disease-associated or benign).     

Testing in Normal Mixture Models with Some Information on the Parameters

The aim of this paper is to study the distribution of the likelihood ratio for testing whether or not one is sampling from a mixture of two distributions or from a single distribution. We study the case where some information is available on the variation range of the parameters of populations. First we study the simplest case in which the difference between the mean of the two populations is known. We show certain distortions between theoretical and simulation results. Secondly, we show how this distortion spreads to the situation where this difference belongs to an interval. Finally, we give an example concerning the detection of major genes in animal population.     

Genome size and metabolic intensity in tetrapods: a tale of two lines

We show the negative link between genome size and metabolic intensity in tetrapods, using the heart index (relative heart mass) as a unified indicator of metabolic intensity in poikilothermal and homeothermal animals. We found two separate regression lines of heart index on genome size for reptiles-birds and amphibians-mammals (the slope of regression is steeper in reptiles-birds). We also show a negative correlation between GC content and nucleosome formation potential in vertebrate DNA, and, consistent with this relationship, a positive correlation between genome GC content and nuclear size (independent of genome size). It is known that there are two separate regression lines of genome GC content on genome size for reptiles-birds and amphibians-mammals: reptiles-birds have the relatively higher GC content (for their genome sizes) compared to amphibians-mammals. Our results suggest uniting all these data into one concept. The slope of negative regression between GC content and nucleosome formation potential is steeper in exons than in non-coding DNA (where nucleosome formation potential is generally higher), which indicates a special role of non-coding DNA for orderly chromatin organization. The chromatin condensation and nuclear size are supposed to be key parameters that accommodate the effects of both genome size and GC content and connect them with metabolic intensity. Our data suggest that the reptilian-birds clade evolved special relationships among these parameters, whereas mammals preserved the amphibian-like relationships. Surprisingly, mammals, although acquiring a more complex general organization, seem to retain certain genome-related properties that are similar to amphibians. At the same time, the slope of regression between nucleosome formation potential and GC content is steeper in poikilothermal than in homeothermal genomes, which suggests that mammals and birds acquired certain common features of genomic organization.     

Biomass and biodiversity in species-rich tritrophic communities

We consider a tritrophic system with one basal and one top species and a large number of primary consumers, and derive upper and lower bounds for the total biomass of the middle trophic level. These estimates do not depend on dynamical regime, holding for fixed point, periodic, or chaotic dynamics. We have two kinds of estimates, depending on whether the predator abundance is zero. All these results are uniform in a self-limitation parameter, which regulates prey diversity in the system. For strong self-limitation, diversity is large; for weak self-limitation, it is small. Diversity depends on the variance of species’ parameter values. The larger this variance, the lower the diversity, and vice versa. Moreover, variation in the parameters of the Holling type II functional response changes the bifurcation character, with the equilibrium state with nonzero predator abundance losing stability. If that variation is small then the bifurcation can lead to oscillations (the Hopf bifurcation). Under certain conditions, there exists a supercritical Hopf bifurcation. We then find a connection between diversity and Hopf bifurcations. We also show that the system exhibits top-down regulation and a hump-shaped diversity-productivity curve.We then extend the model by allowing species to experience self-regulation. For this extended model, explicit estimates of prey diversity are obtained. We study the dynamics of this system and find the following. First, diversity and system dynamics crucially depend on variation in species parameters. We show that under certain conditions, the system undergoes a supercritical Hopf bifurcation. We also establish a connection between diversity and Hopf bifurcations. For strong self-limitation, diversity is large and complex dynamics are absent. For weak self-limitation, diversity is small and the equilibrium with non-zero predator abundance is unstable.     

On the stability of metabolic cycles

We investigate the stability properties of two different classes of metabolic cycles using a combination of analytical and computational methods. Using principles from structural kinetic modeling (SKM), we show that the stability of metabolic networks with certain structural regularities can be studied using a combination of analytical and computational techniques. We then apply these techniques to a class of single input, single output metabolic cycles, and find that the cycles are stable under all conditions tested. Next, we extend our analysis to a small autocatalytic cycle, and determine parameter regimes within which the cycle is very likely to be stable. We demonstrate that analytical methods can be used to understand the relationship between kinetic parameters and stability, and that results from these analytical methods can be confirmed with computational experiments. In addition, our results suggest that elevated metabolite concentrations and certain crucial saturation parameters can strongly affect the stability of the entire metabolic cycle. We discuss our results in light of the possibility that evolutionary forces may select for metabolic network topologies with a high intrinsic probability of being stable. Furthermore, our conclusions support the hypothesis that certain types of metabolic cycles may have played a role in the development of primitive metabolism despite the absence of regulatory mechanisms.     

The effect of haemolysis on certain canine serum chemistry parameters

Haemolysis has been known to cause artefacts in certain canine serum chemistry parameters. These parameters are often used by researchers to detect toxicity in certain studies; haemolysis, therefore, can make serum chemistry interpretation very difficult. In order to determine whether a relationship existed between the level of haemolysis and certain canine serum chemistry parameters, haemolysis was artificially induced by adding a haemolysate of known haemoglobin concentration to serum specimens. A routine clinical chemistry profile was performed on each specimen. Statistical analyses were performed on the results to examine the relationship between level of haemolysis and serum chemistry results. Interpretation of serum chemistry results of haemolysed canine sera paralleled, in most cases, human historical data.     

Grasshopper calling songs convey information about condition and health of males

Females of the grasshopper Chorthippus biguttulus invest much more in the offspring than do males. As a consequence, females are the more selective sex and exert a sexual selection on males by responding to the songs of certain conspecific males while rejecting others. What kind of information about the sender may a female obtain from a male’s song, in addition to its species identity? We searched for correlations between a series of song features and morphometric parameters of individual males. In addition, also the immunocompetence of males was assessed by implanting small pieces of nylon thread. We found significant, positive correlations between certain song characteristics and indicators of male size and immunocompetence. Thus, grasshopper females may—in principle—be able to judge a male’s condition and health from the acoustic signals he produces.     

RecA force generation by hydrolysis waves

We present a simple theory of the dynamics of force generation by RecA during homologous strand exchange and a continuous, deterministic mathematical model of the proposed process. Calculations show that force generation is possible in this model for certain reasonable values of the parameters. We predict the shape of the force-velocity curve for the Holliday junction, which exhibits a distinctive kink at large retarding force, and suggest experiments which should distinguish between the proposed model and other models in the literature.     

Short Barcodes for Next Generation Sequencing

We consider the design and evaluation of short barcodes, with a length between six and eight nucleotides, used for parallel sequencing on platforms where substitution errors dominate. Such codes should have not only good error correction properties but also the code words should fulfil certain biological constraints (experimental parameters). We compare published barcodes with codes obtained by two new constructions methods, one based on the currently best known linear codes and a simple randomized construction method. The evaluation done is with respect to the error correction capabilities, barcode size and their experimental parameters and fundamental bounds on the code size and their distance properties. We provide a list of codes for lengths between six and eight nucleotides, where for length eight, two substitution errors can be corrected. In fact, no code with larger minimum distance can exist.     

Relationships between Platelets and Blood Cells in Postprandial Glycemia in Healthy Individuals

The relationships between platelet aggregation and blood cell amount were studied in healthy subjects after fasting and after a standard carbohydrate breakfast. Positive relationships were revealed between certain parameters of platelet aggregation and the amounts of monocytes and eosinophils. Negative relationships were revealed between most parameters of platelet aggregation and the amount of platelets. Along with the well-known food leukocytosis and increased fibrinogen, postprandial conditions were characterized by an increase in certain parameters of platelet aggregation, destruction of the relationship between the fibrinogen concentration and platelet aggregation, impairment of the inverse relationship between the amount and aggregation of platelets, and moderate direct or inverse relationships between certain parameters of the first and the second stages of platelet aggregation and the erythrocyte parameters. As a disturbing factor, postprandial conditions activated platelet hemostasis by modulating the initial stages of aggregation and substantially changed the interrelations between blood cells.     

Characteristics of Poaceae pollen grains as a tool to assess palaeoecological grassland dynamics in South America

Despite the dominance of grasslands during the last glacial period, especially in South America, the highly uniform morphology of Poaceae pollen grains has so far allowed only very few palynological studies based on Poaceae pollen. In our study we compare two methods of distinguishing between South American grassland ecosystems based on quantitative morphology of Poaceae pollen grains. We investigated data sets from Páramo in southern Ecuador, Campos de Altitude and Campos in south-eastern and southern Brazil as well as data sets from the Pampa in Argentina by measuring the pollen grain length, grain width, pore diameter and annulus width. Firstly we investigated the potential influence of chemical treatment of pollen grains on pollen grain size as well as the measurement setting for defining the boundary conditions for using Poaceae pollen grains in a palaeoecological investigation. Finally the measured pollen grain parameters were analyzed by comparison of average grain length using statistical tests. This approach reveals highly significant differences in average grain size between all grassland ecosystems. Assuming that a certain grain size range can be assigned to a certain Poaceae taxon, conclusions about differences and similarities in taxa composition can be derived. We used two methods of multivariate data analysis. One uses the pollen grain parameters directly for a Principle Component Analysis (PCA). The other is an already established method in grassland ecology which defines parameter based pollen grain types to investigate similarities between grassland ecosystems. Both approaches confirm the results of the grain length analysis. In this work we demonstrate that the method we developed has the potential to provide acquisition of so far inaccessible information on spatial and temporal patterns and dynamics of South American grasslands.     

The effect of lipid demixing on the electrostatic interaction of planar membranes across a salt solution

We study the effect of lipid demixing on the electrostatic interaction of two oppositely-charged membranes in solution, modeled here as an incompressible two-dimensional fluid mixture of neutral and charged mobile lipids. We calculate, within linear and nonlinear Poisson-Boltzmann theory, the membrane separation at which the net electrostatic force between the membranes vanishes, for a variety of different system parameters. According to Parsegian and Gingell, contact between oppositely-charged surfaces in an electrolyte is possible only if the two surfaces have exactly the same charge density (sigma(1) = -sigma(2)). If this condition is not fulfilled, the surfaces can repel each other, even though they are oppositely charged. In our model of a membrane, the lipidic charge distribution on the membrane surface is not homogeneous and frozen, but the lipids are allowed to freely move within the plane of the membrane. We show that lipid demixing allows contact between membranes even if there is a certain charge mismatch, /sigma(1)/ not equal /sigma(2)/, and that in certain limiting cases, contact is always possible, regardless of the value of sigma(1)/sigma(2) (if sigma(1)/sigma(2) < 0). We furthermore find that of the two interacting membranes, only one membrane shows a major rearrangement of lipids, whereas the other remains in exactly the same state it has in isolation and that, at zero-disjoining pressure, the electrostatic mean-field potential between the membranes follows a Gouy-Chapman potential from the more strongly charged membrane up to the point of the other, more weakly charged membrane.     

Sampling rate effects on measurements of correlated and biased random walks

When observing the two-dimensional movement of animals or microorganisms, it is usually necessary to impose a fixed sampling rate, so that observations are made at certain fixed intervals of time and the trajectory is split into a set of discrete steps. A sampling rate that is too small will result in information about the original path and correlation being lost. If random walk models are to be used to predict movement patterns or to estimate parameters to be used in continuum models, then it is essential to be able to quantify and understand the effect of the sampling rate imposed by the observer on real trajectories. We use a velocity jump process with a realistic reorientation model to simulate correlated and biased random walks and investigate the effect of sampling rate on the observed angular deviation, apparent speed and mean turning angle. We discuss a method of estimating the values of the reorientation parameters used in the original random walk from the rediscretized data that assumes a linear relation between sampling time step and the parameter values.     

A Hidden Markov Model for Single Particle Tracks Quantifies Dynamic Interactions between LFA-1 and the Actin Cytoskeleton

The extraction of hidden information from complex trajectories is a continuing problem in single-particle and single-molecule experiments. Particle trajectories are the result of multiple phenomena, and new methods for revealing changes in molecular processes are needed. We have developed a practical technique that is capable of identifying multiple states of diffusion within experimental trajectories. We model single particle tracks for a membrane-associated protein interacting with a homogeneously distributed binding partner and show that, with certain simplifying assumptions, particle trajectories can be regarded as the outcome of a two-state hidden Markov model. Using simulated trajectories, we demonstrate that this model can be used to identify the key biophysical parameters for such a system, namely the diffusion coefficients of the underlying states, and the rates of transition between them. We use a stochastic optimization scheme to compute maximum likelihood estimates of these parameters. We have applied this analysis to single-particle trajectories of the integrin receptor lymphocyte function-associated antigen-1 (LFA-1) on live T cells. Our analysis reveals that the diffusion of LFA-1 is indeed approximately two-state, and is characterized by large changes in cytoskeletal interactions upon cellular activation.     

Parameters of exponentially damped sinusoids in noise and their application to the analysis of visual evoked potentials

The backward prediction and singular value (SV) truncation methods for estimating multiple exponentially damped real sinusoids in noise have been studied. The basic theory and algorithm are outlined, and the effect on the error of computational parameters, such as the sampling window, the sampling rate, the order of the prediction-error filter (PEF) and the truncated point of SV, were studied using simulated data. If the computational parameters are carefully chosen, the estimate of frequency and damping factor of a damped sinusoid is quite accurate (within a certain range of signal to noise (S/N) ratio). We use this method to estimate the parameters of visual evoked potentials (VEP) and then reconstructed them from estimated parameters according to the resonant model. The error between original VEP and the reconstructed waveform is within 5%. This method can be used in the analysis and recognition of various systems.     

Oscillating spatial structures of a tissue

We present a simple mathematical model for the self-controlled growth of a tissue giving rise to an oscillating tissue size under certain conditions. The control is brought about by two substances (two inhibitors or one inhibitor and one nutrient) which influence the cell kinetics locally. The inhibitors are produced by the tissue itself (whereas the nutrient comes from outside but is consumed by the tissue which produces the same effect). Both diffuse freely throughout the tissue, and thus realize a communication between different parts of the tissue. In any case the tissue approaches a self-maintaining space-time structure with properties depending on the parameters of proliferation, death and inhibiting control. We discuss the conditions for this structure not to be time-independent but oscillating.     

Generation of grouped discharges by tectal projection cells

In this paper we briefly summarize our recent data on the transduction properties of tecto-bulbo-spinal neurons (TBSN) in the cat. These neurons from an important link between the superior colliculus and the "premotor" structures of the brain stem and the cervical spinal cord. They are closely similar to spinal alpha-motoneurons, as concerns the soma-dendritic geometry and electrotonic parameters. In contrast, their rhythmic firing behavior is characterized by much higher sensitivity to depolarizing currents and by the capability ot generate extraspikes ("regenerative firing mode"). This results in an abrupt increase of sensitivity when a certain limit of depolarization is surpassed. Membrane parameters of TBSN which are responsible for their characteristic transduction properties are presented. We forward an hypothesis that different modes of rhythmic firing, as dependent on behavioral situation, play a role in the distribution of efferent signals among many different target areas of TBSNs.     

The effect of risk-taking behaviour in epidemic models

We study an epidemic model that incorporates risk-taking behaviour as a response to a perceived low prevalence of infection that follows from the administration of an effective treatment or vaccine. We assume that knowledge about the number of infected, recovered and vaccinated individuals has an effect in the contact rate between susceptible and infectious individuals. We show that, whenever optimism prevails in the risk behaviour response, the fate of an epidemic may change from disease clearance to disease persistence. Moreover, under certain conditions on the parameters, increasing the efficiency of vaccine and/or treatment has the unwanted effect of increasing the epidemic reproductive number, suggesting a wider range of diseases may become endemic due to risk-taking alone. These results indicate that the manner in which treatment/vaccine effectiveness is advertised can have an important influence on how the epidemic unfolds.