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[Therapy and institutions: size and internal communications of the therapeutics framework system].

This study describes the collaboration effort between professionals of different institutions who are engaged in a multifocal therapeutic framing of an at-risk family. Detriangulation of the professionals out of the family system is emphasized, through the progressive establishment of internal and external communication rules, and through the progressive reduction of the team's dimension. Reference is made to a systemic evolutive model.

Communication↗
PubMed1976

Mechanisms involved in elimination of organisms from experimental cutaneous Candida albicans infections in guinea pigs.

Experimental cutaneous Candida albicans infections were produced in guinea pigs either by using occlusive dressings over the organisms or by applying them to the shaved skin directly without occlusive dressings. In either model there was clearance of the infecting organisms from the skin by a process involving profuse scaling of the keratinized layer in which they were confined. However, for each type of infection the mechanisms producing this scaling seemed to involve different parts of the host defense system. Infections produced under occlusive dressings were characterized by a rapid accumulation of polymorphonuclear leukocytes (PMN) in the epidermis and formation of thick crusts in which organisms were trapped. Sloughing of the crust removed the organisms. In this model, evolution of the lesions and the rate of clearance of the organisms did not depend on prior immunity to Candida. Two possible mechanisms for attraction of PMN into the lesions were direct activation of the alternative complement pathway by the organisms in the lesions and direct chemotactic activity in components of Candida albicans. In contrast, infections produced without occlusive dressings showed only minimal epidermal PMN infiltration, but also underwent profuse scaling of the keratinized layer. This response appeared to depend on cell-mediated immunity. Only animals with previously-acquired delayed hypersensitivity to Candida antigens could undergo this type of scaling, and indeed, this response was transferable to nonimmue animals with peritoneal exudate cells from Candida-immune animals. Clearance of the infecting organisms from this type of infection was significantly faster in immune than in nonimmune animals. It is postulated that a lymphokine released from lymphocytes in the upper epidermis acts on epidermal cells to increase the rate of keratin turnover either by the mitotic rate of the germinal cells or by increasing their rate of keratinization.

Animals↗
PubMed1995

Properties of a general model of DNA evolution under no-strand-bias conditions.

Under the hypothesis of no-strand-bias conditions, the Watson and Crick base-pairing rule decreases the complexity of models of DNA evolution by reducing to six the maximum number of substitution rates. It was shown that intrastrand equimolarity between A and T (A*=T*) and between G and C (G*=C*) [corrected] is a general asymptotic property of this class of models. This statistical prediction was observed on 60 long genomic fragments (> 50 kbp) from various kingdoms, even when the effect of the two opposite orientations for coding sequences is removed. The practical consequence of the model for estimating the expected number of substitutions per site between two homologous DNA sequences is discussed.

Biological Evolution↗
PubMed1990

Development of a spin-glass model of prebiotic evolution: environmental effects on ensembles of genetic polymers.

We develop in two ways an existing spin-glass model of prebiotic polymer evolution. First, by choosing the environment J in a prescribed manner, similar to neural network presciptions, we may create an environment which favors a linearly independent set of evolutionary niches (Ea). That is, we may control which polymer "species" will evolve in our system. Computer simulations confirm this result. We obtain a quantitative value for the sharpness of a niche. Second, we extend the model by allowing a surviving polymer to act upon--to "remold"--its environment; the nature of the environmental action is governed by the "molding" matrix M. When the mold M is the identity matrix, the feedback algorithm reduces to a Hebb learning algorithm form, and a surviving polymer acts to enhance its own survival prospects. Molds having a structure analogous to (temporal) associative memories in neural networks can generate autocatalytic species or can exhibit symbiotic interspecies relationships.

Biological Evolution↗
PubMed1998

Models for haplotype evolution in a nonstationary population.

Haplotype mapping has emerged in the past few years as a powerful tool for the fine mapping of disease genes. It is typically carried out on a sample of affected individuals from a population isolate. If the chromosome neighborhood of a disease gene is saturated with markers, then each new mutation in the population or existing mutation introduced by a population founder exhibits a unique haplotype signature at the time of its introduction. Partial disruption of these signatures by recombination can be visualized in affects and provide important clues to the location of the disease gene. The current paper models haplotype evolution with the intention of clarifying the most favorable circumstances for haplotype mapping. Comparisons with linkage mapping are stressed. For dominant diseases, both deterministic and stochastic models are suggested. Numerical examples based on Finnish population parameters illustrate the general theory in the presence of the complications of selection, mutation, and slow, exponential growth of the isolate.

Biological Evolution↗
PubMed2000

The codon-degeneracy model of molecular evolution.

Mitochondrial genetic codons can be categorized by four patterns of nucleotide-site degeneracy based on varying combinations of twofold- or nondegenerate sites at first codon positions and twofold- or fourfold-degenerate sites at third codon positions. Herein, a model of molecular evolution is introduced that uses these patterns to calculate expected substitution frequencies for each codon position and substitution type relative to overall number of synonymous or nonsynonymous substitutions. Regions of the pocket gopher cytochrome oxidase subunit I (COI) and cytochrome b (cyt-b) genes are analyzed using this model. Chi-square distributions are used to produce relative goodness-of-fit (GF) scores for measuring the difference between substitution frequencies predicted by the codon-degeneracy model (CDM), and frequencies inferred using a well-supported phylogenetic tree of closely related species. The GF scores for expected and observed synonymous (GF(syn) = 0.429, p = 0.807) and nonsynonymous (GF(ns) = 2.309, p = 0.679) substitution frequencies resulted in a failure to reject the CDM as a null hypothesis for the molecular evolution of COI and cyt-b in pocket gophers. Alternative tree topologies and calculations of transition bias for these data result in higher GF scores.

Animals↗
PubMed2001

A putative insect intracellular endosymbiont stem clade, within the Enterobacteriaceae, infered from phylogenetic analysis based on a heterogeneous model of DNA evolution.

Insect intracellular symbiotic bacteria (intracellular endosymbionts, or endocytobionts) were positioned within the gamma 3-Proteobacteria using a non-homogeneous model of DNA evolution, allowing for rate variability among sites, for GC content heterogeneity among sequences, and applied to a maximum likelihood framework. Most of them were found to be closely related within the Enterobacteriaceae family, located between Proteus and Yersinia. These results suggest that such a bacterial group might possess several traits allowing for insect infection and the stable establishment of symbiotic relationships and that this could represent a stem clade for numerous insect endocytobionts. Based on the estimations of the equilibrium GC content and branch lengths in the phylogenetic tree, we have made comparisons of the relative ages of these different symbioses.

Animals↗
PubMed1994

Structure of homeobox-leucine zipper genes suggests a model for the evolution of gene families.

Homeobox genes are present in both plants and animals. Homeobox-leucine zipper genes, however, have been identified thus far only in the small mustard plant Arabidopsis thaliana. This observation suggests that homeobox-leucine zipper genes evolved after the divergence of plants and animals, perhaps to mediate specific regulatory events. To better understand this gene family, we isolated several sequences containing the homeobox-leucine zipper motif and carried out a comparative analysis of nine homeobox-leucine zipper genes (HAT1, HAT2, HAT3, HAT4, HAT5, HAT7, HAT9, HAT14, and HAT22). Gene structures, sequence comparisons, and chromosomal locations suggest a simple model for the evolution of these genes. The model postulates that a primordial homeobox gene acquired a leucine zipper by exon capture. The nascent homeobox-leucine zipper gene then appears to have undergone a series of gene duplication and chromosomal translocation events, leading to the formation of the HAT gene family. This work has general implications for the evolution of regulatory genes.

Arabidopsis↗
PubMed2004

MCALIGN: stochastic alignment of noncoding DNA sequences based on an evolutionary model of sequence evolution.

A method is described for performing global alignment of noncoding DNA sequences based on an evolutionary model parameterized by the frequency distribution of lengths of insertion/deletion events (indels) and their rate relative to nucleotide substitutions. A stochastic hill-climbing algorithm is used to search for the most probable alignment between a pair of sequences or three sequences of known phylogenetic relationship. The performance of the procedure, parameterized according to the empirical distribution of indel lengths in noncoding DNA of Drosophila species, is investigated by simulation. We show that there is excellent agreement between true and estimated alignments over a wide range of sequence divergences, and that the method outperforms other available alignment methods.

Algorithms↗
PubMed1995

Saltationist and punctuated equilibrium models for the evolution of viviparity and placentation.

Vertebrate viviparity (live-bearing reproduction), placentation, and placentotrophy are widely assumed to have evolved as three successive, gradualistic transformations. From empirical data and predictive tests on lizards and snakes, this paper indicates that placentae and a degree of placentotrophy have evolved repeatedly as necessary correlates of viviparity, not as subsequent modifications. In addition, information derived from studies of anatomy, physiology, biogeography and systematics is used to evaluate new saltationist and punctuated equilibrium models for the evolution of viviparity. Phylogenetic reconstruction reveals that more than 100 squamate clades have made the transition to viviparity and placentation. However, various phenotypic intermediates postulated by the gradualistic model are either scarce or unrepresented among known forms, including those in which viviparity has evolved at specific and subspecific levels. Evolution in squamates seems to have produced a dichotomy between two evolutionarily stable patterns: (i) retention of weakly shelled or shell-free eggs to term (viviparity), with development of fully functional placentae; and (ii) deposition of shelled eggs at or near the limb bud stage of development (typical oviparity). Conflicting functional demands placed on eggshell morphology may constrain establishment of prolonged, oviparous egg-retention as a viable, historically stable pattern. Alternatively, the costs of prolonged egg-retention associated with decreased female mobility or decreased fecundity may exceed the benefits in oviparous forms.

Animals↗
PubMed1990

A polygenic model for the evolution and maintenance of conditional strategies.

We develop a genetic model for conditional strategies which places such strategies in the context of phenotypic plasticity. The model, which treats conditional strategies as polygenic threshold traits, indicates that, given requisite genetic variation in reaction norms, conditional strategies will evolve to their optimum level and be maintained by stabilizing selection, provided environmental variation results in a fitness trade-off for the alternative conditional phenotypes. The precise value for the evolutionary optimum is found to depend primarily on the probability density function of the environmental variation that influences the production of the conditional phenotypes and the magnitude of the fitness trade-offs of the conditional phenotypes across such environmental variation. The model is tested by application to three well-studied conditional strategies. In each case the predictions of the model are in good agreement with the results of these studies.

Animals↗
PubMed1987

A genetic model describing the evolution of levamisole resistance in Trichostrongylus colubriformis, a nematode parasite of sheep.

Data from 21 generations of selection on a levamisole-resistant strain of Trichostrongylus colubriformis, either exposed to selection with the anthelmintics levamisole (LEV) or thiabendazole (TBZ), or unexposed, were used to fit a genetic model describing the evolution of LEV resistance in this parasite species. A statistical model describing the dose-response relationship for a mixed population of susceptible and resistant parasite eggs exposed to anthelmintic was fitted to egg-hatch assay data for each generation and for each selection regimen. Estimated parameters from the statistical model provided the input for the genetic model from which were obtained estimates of the relative fitness of susceptible and resistant genotypes under each selection regimen. The experimental data and the genetic models both indicated that, in this parasite strain, LEV resistance was determined by a single dominant gene, and that TBZ selects for LEV susceptibility. A variety of drug alternation programmes was simulated for this genetic system. The programme that minimized the development of LEV resistance involved alternating the drugs (LEV and TBZ) between each worm generation.

Animals↗
PubMed2000

A skew model for the evolution of sociality via manipulation: why it is better to be feared than loved.

Concession-based reproductive skew models predict that social groups can form via persuasion, whereby dominant individuals forfeit some reproduction to subordinates as an incentive to stay and help. We have developed an alternative skew model based on manipulation, whereby dominant individuals coerce subordinates into staying and helping by imposing costs on their independent reproductive prospects. Stable groups can evolve under a much wider range of genetic and ecological conditions under this manipulation model than under concession models. We describe evidence that various forms of pre-emptive and ongoing manipulation occur in nature and we discuss the implications of the model for the development of a general theory of social evolution.

Animals↗
PubMed2000

Fitness differences among diploids, tetraploids, and their triploid progeny in Chamerion angustifolium: mechanisms of inviability and implications for polyploid evolution.

Theoretical models indicate that the evolution of tetraploids in diploid populations will depend on both the relative fitness of the tetraploid and that of the diploid-tetraploid hybrids. Hybrids are believed to have lower fitness due to imbalances in either the ploidy (endosperm imbalance) or the ratio of maternal to paternal genomes in their endosperm (genomic imprinting). In this study we created diploids, tetraploids, and hybrid triploids of Chamerion angustifolium from crosses between field-collected diploid and tetraploid plants and evaluated them at six life stages in a greenhouse comparison. Diploid offspring (from 2x x 2x crosses) had significantly higher seed production and lower biomass than tetraploid offspring (from 4x x 4x crosses). Relative to the diploid, the cumulative fitness of tetraploids was 0.67. In general, triploids (from 2x x 4x, 4x x 2x crosses) had significantly lower seed production, lower pollen viability, and higher biomass than diploid individuals. Triploid offspring derived from diploid maternal parents had lower germination rates, but higher pollen production than those with tetraploid mothers. Relative to diploids, the cumulative fitness of 2x x 4x triploids and 4x x 2x triploids was 0.12 and 0.06, respectively, providing some support for effect of differing maternal:paternal ratios and endosperm development as a mechanism of hybrid inviability. Collectively, the data show that tetraploids exhibit an inherent fitness disadvantage, although the partial viability and fertility of triploids may help to reduce the barrier to tetraploid establishment in sympatric populations.

Biological Evolution↗
PubMed1998

A codon-based model designed to describe lentiviral evolution.

A codon-based model designed to describe lentiviral evolution is developed. The model incorporates unequal base compositions in the three codon positions and selection against the CpG dinucleotide within codons to account for a deficit of this dinucleotide exhibited by lentiviral genes. The model is, to a large extent, able to account for the pattern of codon usage exhibited by the HIV1 genes gag, pol, and env, in spite of its parameter paucity. The model is extended to a similar model which operates on pentets (codons and their neighboring bases). The results obtained by the pentet model establish the importance of depression of CpGs across codon boundaries as well as within codons. The goodness of fit of the CpG depression model to the observed evolution in pairwise alignments of HIV1 sequences is assessed. The model provides a significantly better description of the observed evolution than the simpler models examined. The parameter estimates indicate that part of the unusually large biases in nucleotide frequencies observed in HIV1 genes is caused by selection against CpGs. We find that the estimates of expected numbers of substitutions, of transitions to transversions, and of synonymous to nonsynonymous substitution rates are robust to CpG depression, whereas the ratio of CpG-generating substitutions to other substitutions is strongly influenced by the choice of model.

Base Composition↗