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At least 649 records · Page 36Linked to original sources

A cellular automaton model for the study of DNA sequence evolution.

Cellular automata are introduced as a model for DNA structure, function and evolution. DNA is modeled as a one-dimensional cellular automaton with four states per cell. These states are the four DNA bases A, C, T and G. The four states are represented by numbers of the quaternary number system. Linear evolution rules, represented by square matrices, are considered. Based on this model a simulator of DNA evolution is developed and simulation results are presented. This simulator has a user-friendly input interface and can be used for the study of DNA evolution.

Evolution, Molecular↗

Testing genetic models of mate choice evolution in the wild.

Understanding the mechanisms driving the evolution of mate choice, particularly the importance of indirect genetic benefits, remains a challenge, especially in wild populations. Three recent studies have attempted to quantify the importance of indirect benefits in wild bird populations using approaches derived from quantitative genetic models of mate choice. In all three cases, no support was found for a role of indirect benefits in the evolution of mate choice. These studies suggest that a quantitative genetic approach can illuminate this long-standing problem and that alternative models for the evolution of mate preferences should be tested in wild populations.

Animals↗

IL-11: insights in asthma from overexpression transgenic modeling.

The evolution of our understanding of IL-11 mirrors, in many ways, the problems that are faced by investigators in the post-genome era and the types of techniques that might need to be used to deal with these issues. IL-11 was discovered as a soluble factor in fibroblast supernatants that stimulated the proliferation of "IL-6-dependent" plasmacytoma cells. It was subsequently demonstrated to be an important stimulator of platelet reconstitution and a pleiotropic regulator of nonrespiratory tissues. In the lung, IL-11 is produced by a variety of structural cells and eosinophils in response to a variety of stimuli, including TGF-beta, major basic proteins, and viruses. IL-11 is also detected in exaggerated quantities at sites of virus infection. Its potential effector functions at these sites were defined with constitutive and inducible overexpression transgenic modeling systems which demonstrated that IL-11 causes nodular mononuclear infiltrates, airway remodeling with subepithelial fibrosis, airways obstruction, and airways hyperresponsiveness and can block alveolar development when expressed during development. In accord with these murine findings, IL-11 is selectively expressed in eosinophils and epithelial cells in patients with moderate and severe asthma where expression correlates directly with disease severity and inversely with FEV(1). Studies using transgenic mice also demonstrated that IL-11 inhibits antigen-induced tissue inflammation. Thus IL-11 might be an important regulator of inflammatory and remodeling responses in the asthmatic airway.

Animals↗

Adaptive branching in evolution and epigenesis.

We describe one of the simplest models that exhibit an adaptive branching behaviour. It is analysed both experimentally and formally, and its successive bifurcations provide a good model of what R. Thom called 'generalized catastrophes'. Two theorems on the stochastic adaptivity of the algorithm to very general shapes of target are given. The model further displays the phenomenon of abortive branching: each macroscopic branching appears after a burst of microscopic branchings that stop growing after a very short time. The mathematical analysis of the model explains why and how this behaviour occurs. Possible applications of these models to Evolution (natural and artificial) and Epigenesis are briefly mentioned, and a higher dimensional version is applied to growing a tree in a space of shapes in the context of a database of medical images.

Adaptation, Physiological↗

Pharmacological activities in thermal proteins: relationships in molecular evolution.

The model of protobiological events that has been presented in these pages has increasing relevance to pharmacological research. The thermal proteins that function as key substances in the proteinoid theory have recently been found to prolong the survival of rat forebrain neurons in culture and to stimulate the growth of neurites. A search for such activity in thermal proteins added to cultures of modern neurons was suggested by the fact that some of the microspheres assembled from proteinoids rich in hydrophobic amino acids themselves generate fibrous outgrowths.

Amino Acids↗

Mathematical model of diffusion-limited evolution of multiple gas bubbles in tissue.

Models of gas bubble dynamics employed in probabilistic analyses of decompression sickness incidence in man must be theoretically consistent and simple, if they are to yield useful results without requiring excessive computations. They are generally formulated in terms of ordinary differential equations that describe diffusion-limited gas exchange between a gas bubble and the extravascular tissue surrounding it. In our previous model (Ann. Biomed. Eng. 30: 232-246, 2002), we showed that with appropriate representation of sink pressures to account for gas loss or gain due to heterogeneous blood perfusion in the unstirred diffusion region around the bubble, diffusion-limited bubble growth in a tissue of finite volume can be simulated without postulating a boundary layer across which gas flux is discontinuous. However, interactions between two or more bubbles caused by competition for available gas cannot be considered in this model, because the diffusion region has a fixed volume with zero gas flux at its outer boundary. The present work extends the previous model to accommodate interactions among multiple bubbles by allowing the diffusion region volume of each bubble to vary during bubble evolution. For given decompression and tissue volume, bubble growth is sustained only if the bubble number density is below a certain maximum.

Air Pressure↗

Lessons from the Australian Patient Safety Foundation: setting up a national patient safety surveillance system--is this the right model?

The evolution of the concepts and processes underpinning the Australian Patient Safety Foundation's systems over the last 15 years are traced. An ideal system should have the following attributes: an independent organisation to coordinate patient safety surveillance; agreed frameworks for patient safety and surveillance systems; common, agreed standards and terminology; a single, clinically useful classification for things that go wrong in health care; a national repository for information covering all of health care from all available sources; mechanisms for setting priorities at local, national and international levels; a just system which caters for the rights of patients, society, and healthcare practitioners and facilities; separate processes for accountability and "systems learnings"; the right to anonymity and legal privilege for reporters; systems for rapid feedback and evidence of action; mechanisms for involving and informing all stakeholders. There are powerful reasons for establishing national systems, for aligning terminology, tools and classification systems internationally, and for rapid dissemination of successful strategies.

Australia↗

Locus specificity of polymorphic alleles and evolution by a birth-and-death process in mammalian MHC genes.

We have conducted an extensive phylogenetic analysis of polymorphic alleles from human and mouse major histocompatibility complex (MHC) class I and class II genes. The phylogenetic tree obtained for 212 complete human class I allele sequences (HLA-A, -B, and -C) has shown that all alleles from the same locus form a single cluster, which is highly supported by bootstrap values, except for one HLA-B allele (HLA-B*7301). Mouse MHC class I loci did not show locus-specific clusters of polymorphic alleles. This was considered to be because of either interlocus genetic exchange or the confusing designation of loci in different haplotypes at the present time. The locus specificity of polymorphic alleles was also observed in human and mouse MHC class II loci. It was therefore concluded that interlocus recombination or gene conversion is not very important for generating MHC diversity, with a possible exception of mouse class I loci. According to the phylogenetic trees of complete coding sequences, we classified human MHC class I (HLA-A, -B, and -C) and class II (DRB1) alleles into three to five major allelic lineages (groups), which were monophyletic with high bootstrap values. Most of these allelic groups remained unchanged even in phylogenetic trees based on individual exons, though this does not exclude the possibility of intralocus recombination involving short DNA segments. These results, together with the previous observation that MHC loci are subject to frequent duplication and deletion, as well as to balancing selection, indicate that MHC evolution in mammals is in agreement with the birth-and-death model of evolution, rather than with the model of concerted evolution.

Alleles↗

A chronic MPTP model reproducing the slow evolution of Parkinson's disease: evolution of motor symptoms in the monkey.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism both in man and non-human primates. Several models have now been developed, but acute MPTP administration does not consistently reproduce all the clinical features of the disease. To mirror the slow evolution observed in human pathology, a chronic model of intoxication is necessary. The present study describes a chronic MPTP protocol in the monkey. Six monkeys received daily injections of MPTP (0.2 mg/kg i.v.) until they reached a score over 8 on the clinical rating scale (15.5 days +/- 1.1). Full parkinsonism was first obtained on the 22nd day. Levodopa testing (20 mg/kg per os) alleviated motor abnormalities (51%), proving the parkinsonian nature of these disturbances. Histological lesions reproduced those observed in Parkinson's disease with a decrease in tyrosine hydroxylase immunoreactivity of 90%. This model so could be of great interest for the study of the dynamic physiopathological changes which occur in Parkinson's disease and consequently for research on new neuroprotective therapies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Model parameterization, prior distributions, and the general time-reversible model in Bayesian phylogenetics.

Bayesian phylogenetic methods require the selection of prior probability distributions for all parameters of the model of evolution. These distributions allow one to incorporate prior information into a Bayesian analysis, but even in the absence of meaningful prior information, a prior distribution must be chosen. In such situations, researchers typically seek to choose a prior that will have little effect on the posterior estimates produced by an analysis, allowing the data to dominate. Sometimes a prior that is uniform (assigning equal prior probability density to all points within some range) is chosen for this purpose. In reality, the appropriate prior depends on the parameterization chosen for the model of evolution, a choice that is largely arbitrary. There is an extensive Bayesian literature on appropriate prior choice, and it has long been appreciated that there are parameterizations for which uniform priors can have a strong influence on posterior estimates. We here discuss the relationship between model parameterization and prior specification, using the general time-reversible model of nucleotide evolution as an example. We present Bayesian analyses of 10 simulated data sets obtained using a variety of prior distributions and parameterizations of the general time-reversible model. Uniform priors can produce biased parameter estimates under realistic conditions, and a variety of alternative priors avoid this bias.

Animals↗

A new model for discrete character evolution.

The paper provides an explicit justification for the principle that a uniform taxon should contribute only one datapoint in comparative analyses with discrete variables. The justification is that phylogenetic patterns in variables unincluded in the proposed test vitiate the assumption of independence, both at the level of species and at the level of branch segments. The consequence is that a uniform taxon cannot safely be counted as more than one datapoint. The arguments use a branching discrete Markov process in continuous time, with the new feature that the tested variables are only a subset of the evolving characters. This model is proposed as a useful criterion for measuring the merit of proposed tests, and illustrates the necessity for models in evaluating comparative methods.

Adaptation, Biological↗

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model.

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.

Angiography↗

Models of intracellular transport and evolution of the Golgi complex.

We have performed a systematic analysis of models explaining the mechanisms of the intracellular biosecretory transport. The models assessed include not only those based on one mechanism (the dissociation model (and its individual case, the vesicular model), the progression model (and its individual cases, the cisterna maturation/progression and the carrier maturation models), and the lateral diffusion model (and its individual case, the bolus model), but also combined models of transport (the percolating-vesicles model and the synthetic model), including several transport mechanisms. Most of these models are not able to explain recent data on the evolution of genes involved in intracellular transport and Golgi evolution. The carrier maturation model proposing that fusion of the large cargo domain with the distal (closer to the plasmalemma) compartment precedes fission of the domain from the proximal compartment exhibits the best performance in correlation with the available information on evolution of the biosecretory pathway.

Biological Evolution↗

A population genetic study of the evolution of SINEs. II. Sequence evolution under the master copy model.

A transient population genetic model of SINE (short interspersed repetitive element) evolution assuming the master copy model is theoretically investigated. Means and variances of consensus frequency of nucleotides, nucleotide homozygosity, and the number of shared differences that are considered to have caused by mutations occurring in the master copy lineages are computed. All quantities investigated are shown to be monotone functions of the duration of the expansion period. Thus, they can be used to estimate the expansion period although their sampling variances are generally large. Using the theoretical results, the Sb subfamily of human Alu sequences is analyzed. First, the expansion period is estimated from the observed mean and variance of homozygosity. The expansion period is shown to be short compared to the time since the end of the expansion of the subfamily. However, the observed number of the shared differences is more than twice that expected under the master copy model with the estimated expansion period. Alternative models including that with multiple master copy loci to explain this observation are discussed.

Animals↗

Using artificial evolution and selection to model insect navigation.

BACKGROUND: An animal's behavioral strategies are often constrained by its evolutionary history and the resources available to it. Artificial evolution allows one to manipulate such constraints and explore how they influence evolved strategies. Here we compare the navigational strategies of flying insects with those of artificially evolved "animats" endowed with various motor architectures. Using evolutionary algorithms, we generated artificial neural networks that controlled a virtual animat's navigation within a 2D, simulated world. Like a flying insect, the animat possessed motors that generated thrust and torque, a compass, and visual sensors. Some animats were limited to forward motion, while others could also move sideways. Animats were selected for the precision with which they reached a target specified by a visual landmark. RESULTS: Animats given sideways motors could alter flight direction without changing body orientation and evolved strategies similar to those of flying bees or wasps performing the same task. Both animats and insects first aimed at the landmark. In the last phase, both adopted a fixed body orientation and adjusted their position to keep the landmark at a fixed retinal location. Animats unable to uncouple flight direction and body orientation evolved subtly different strategies and performed less robustly. CONCLUSIONS: This convergence between the navigational strategies of animals and animats suggests that the insect's strategies are primarily an adaptation to the demands of using visual information and compass direction to reach a position in space and that they are not significantly compromised by the insect's evolutionary history.

Animals↗