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Immune response against Leishmania antigens in dogs naturally and experimentally infected with Leishmania infantum.

Cell-mediated and humoral immune response in naturally and experimentally infected dogs was studied using crude and pure antigens. Both types of infections induced severe signs of visceral disease, but the symptoms observed in natural infections were more pronounced than in experimental infections. In addition, asymptomatic infections were not observed in experimentally infected animals. Disease evolution in laboratory infections was rapid and an increase in antibody titer to crude parasite antigen was correlated with the appearance and aggravation of clinical symptoms. Peripheral blood lymphocyte proliferation to crude antigen and pure gp63 was observed early following experimental infection, but was abolished once the infected dogs began to exhibit clinical signs. A similar pattern was observed in naturally infected dogs. Serum from all patent dogs showed high antibody titers to rK39 in enzyme-linked immunosorbent assays (ELISA), and reacted by western blotting with several antigens, 12 to 120 KDa, including gp63 and gp70. In the case of asymptomatic dogs. antibody titers to crude antigen were low and only a few antigens were identified by western blotting. None of the pure proteins examined, gp63, gp70, and rK39 were recognized by western blotting or ELISA. However, asymptomatic dogs exhibited specific lymphocyte proliferation to both crude antigen and the potential vaccine candidate gp63.

Animals↗

Genomic inferences of the cis-regulatory nucleotide polymorphisms underlying gene expression differences between Drosophila melanogaster mating races.

Nucleotide sequence polymorphisms affecting gene expression occur in the regulatory region of genes (in cis) and elsewhere in the genome (in trans). Further study is required to weigh the relative importance of cis- and trans-acting mutations in mediating gene expression differences within and between species. Here, microarray hybridization experiments were used to isolate 363 gene expression differences between the female fly head transcriptomes of 2 Drosophila melanogaster strains. One strain (French) represented the cosmopolitan M mating race and the other strain (ZS30) represented the Z mating race derived from Zimbabwe, Africa. From chromosomal substitution strains engineered from the 2 strains, we inferred that the expression differences between M and Z alleles largely could be attributed to the genotype of the chromosomes where the differentially expressed genes were located, that is, cis-regulatory polymorphisms prominently influence gene expression differences between M and Z. The effects of trans-regulatory polymorphisms were apparent yet difficult to quantify. Results have implications for models of gene regulatory evolution as well as experimental studies trying to identify the nucleotide sequence polymorphisms underlying gene expression differences between Drosophila strains.

Animals↗

Effect of varying epistasis on the evolution of recombination.

Whether recombination decelerates or accelerates a population's response to selection depends, at least in part, on how fitness-determining loci interact. Realistically, all genomes likely contain fitness interactions both with positive and with negative epistasis. Therefore, it is crucial to determine the conditions under which the potential beneficial effects of recombination with negative epistasis prevail over the detrimental effects of recombination with positive epistasis. Here, we examine the simultaneous effects of diverse epistatic interactions with different strengths and signs in a simplified model system with independent pairs of interacting loci and selection acting only on the haploid phase. We find that the average form of epistasis does not predict the average amount of linkage disequilibrium generated or the impact on a recombination modifier when compared to results using the entire distribution of epistatic effects and associated single-mutant effects. Moreover, we show that epistatic interactions of a given strength can produce very different effects, having the greatest impact when selection is weak. In summary, we observe that the evolution of recombination at mutation-selection balance might be driven by a small number of interactions with weak selection rather than by the average epistasis of all interactions. We illustrate this effect with an analysis of published data of Saccharomyces cerevisiae. Thus to draw conclusions on the evolution of recombination from experimental data, it is necessary to consider the distribution of epistatic interactions together with the associated selection coefficients.

Biological Evolution↗

[Cellular mediated immunity in virus infections].

The intervention of cellular immunity in the course of specific antiviral defence is suggested or confirmed by a series of clinical and experimental findings, i.e. the evolution of certain viral diseases following a second contact with viral antigens; discrepancy between the level of antiviral serum antibodies and the clinical course of some viral diseases; pathohistological alterations in some viral diseases, suggesting the intervention of cellular immunity; the clinical aspects of natural or experimental viral diseases in primary and secondary immunodeficiency. Investigations were likewise carried out on certain indices of cellular immunity in human or experimental viral diseases, such as delayed hypersensitivity skin tests; the transfer of immune lymphocytes; lymphocytic blastic transformation; inhibition of macrophage migration; specific cytotoxicity test. The problems concerning the role of cellular immunity in the specific defence against viruses may be grouped as follows: mechanisms of induction of the immune cellular response in viral infections; relationship between cellular and humoral immunity in antiviral resistance; relative independance of systemic and local cellular immunity in the course of viral diseases; the cellular basis of cellular mediated immunity in viral diseases.

Animals↗

Hybridization and the colonization of novel habitats by annual sunflowers.

Although invasive plant species often have a hybrid ancestry, unambiguous evidence that hybridization has stimulated the evolution of invasive behaviors has been difficult to come by. Here, we briefly review how hybridization might contribute to the colonization of novel habitats, range expansions, and invasiveness and then describe work on hybrid sunflowers that forges a direct link between hybridization and ecological divergence. We first discuss the invasion of Texas by the common sunflower and show that the introgression of chromosomal segments from a locally adapted species may have facilitated range expansion. We then present evidence that the colonization of sand dune, desert floor, and salt marsh habitats by three hybrid sunflower species was made possible by selection on extreme or "transgressive" phenotypes generated by hybridization. This body of work corroborates earlier claims regarding the role of hybridization in adaptive evolution and provides an experimental and conceptual framework for ongoing studies in this area.

Biological Evolution↗

Regulatory CD8+ T cells fine-tune the myelin basic protein-reactive T cell receptor V beta repertoire during experimental autoimmune encephalomyelitis.

A significant number of self-reactive T cell clones escape thymic negative selection and are released into the periphery, where some are potentially pathogenic. The clonal expansion of self-reactive T cells is known to be limited during initial antigen encounter by apoptotic or anergic mechanisms, regulatory CD4+ T cells, and cytokines. Here we report that superimposed on these mechanisms, during the evolution of autoimmunity in experimental autoimmune encephalomyelitis (EAE), CD8+ T cells are induced, which fine-tune the peripheral self-reactive T cell receptor (TCR) repertoire. We assayed the myelin basic protein-reactive TCR repertoire in naive, EAE-recovered mice as well as EAE-recovered mice depleted of CD8+ T cells by TCRV beta surface expression, complementarity-determining region 3 length distribution, and complementarity-determining region 3 sequencing analysis. In EAE-recovered mice, certain myelin basic protein-reactive CD4+V beta 8.2+ clones are significantly decreased and this decrease is not observed if CD8+ T cells were depleted from these mice. The clones that persist in CD8+ T cell-intact mice are highly diverse in contrast to the clones expanded in CD8+ T cell-depleted mice, which are dominated by the significant outgrowth of a few clones. Importantly, the T cell clones that expand in the absence of CD8+ T cell control are enriched in potentially pathogenic self-reactive T cell clones capable of inducing EAE in vivo.

Adoptive Transfer↗

Quantum logical operations for spin 3/2 quadrupolar nuclei monitored by quantum state tomography.

This article presents the realization of many self-reversible quantum logic gates using two-qubit quadrupolar spin 3/2 systems. Such operations are theoretically described using propagation matrices for the RF pulses that include the effect of the quadrupolar evolution during the pulses. Experimental demonstrations are performed using a generalized form of the recently developed method for quantum state tomography in spin 3/2 systems. By doing so, the possibility of controlling relative phases of superimposed pseudo-pure states is demonstrated. In addition, many aspects of the effect of the quadrupolar evolution, occurring during the RF pulses, on the quantum operations performance are discussed. Most of the procedures presented can be easily adapted to describe selective pulses of higher spin systems (>3/2) and for spin 1/2 under J couplings.

Journal Article↗

In vitro evolution of molecular cooperation in CATCH, a cooperatively coupled amplification system.

BACKGROUND: One of the key issues in the investigation of evolution is how complex systems evolved from simple chemical replicators. Theoretical work proposed several models in which complex replicating systems are kinetically stabilized. The development of powerful isothermal amplification technique allows complex nucleic acid based evolving in vitro systems to be set up, which may then serve to verify experimentally current theories of evolution. Recently such a system based on the 3SR (self-sustained sequence replication) reaction has been established to investigate the evolution of cooperation: the trans-cooperatively coupled CATCH (cooperative amplification by cross hybridization). RESULTS: Over four rounds of serial transfer, the cooperatively coupled two species CATCH system evolved into a more complex cooperative four species system, which then was overgrown by CATCH-derived RNA-Z-like hairpin species. In contrast to the classical RNA-Z species, these molecules have complementary loop sequences and self-amplify using a dual mechanism that includes concentration-dependent phases of noncooperative and cooperative amplification. CONCLUSIONS: The evolution of a cooperative system, under conditions that were alternately unfavorable and favorable for cooperative amplification, led to a system showing facultative cooperation. This principle of facultative cooperation preserves the complexity of the system investigated and could have general implications for the evolution and stabilization of cooperation under oscillating reaction conditions.

Alfalfa mosaic virus↗

[Four decades since the beginning of Experimental Gastroenterological Surgery at the Peruvian University].

The historic evolution of Peruvian Surgery up to the application of experimentation is described, guiding it on a scientific path. It is evident that the beginning of Experimental Surgery and Laboratories were established, four decades ago, in Peruvian Universities; this enabled other surgical center to introduce new surgical procedures to medical practice. The first experiments in gastrointestinal surgery performed by a surgical school of the UNMSM and in the UPCH as well as their clinical applications in two Teaching Hospitals (Loayza and Cayetano Heredia) are reviewed.

Animals↗

Learning from directed evolution: Further lessons from theoretical investigations into cooperative mutations in lipase enantioselectivity.

An earlier experimental study, which involved the directed evolution of enantioselective lipase variants from Pseudomonas aeruginosa as catalysts in the hydrolytic kinetic resolution of 2-methyl-decanoic acid p-nitrophenyl ester, provided a mutant with six mutations. Consequently, the selectivity factor was found to increase from E = 1.1 for the wild-type to E = 51 for the best mutant. Only one of the amino acid exchanges in this mutant was found to occur next to the binding pocket, the other mutations being remote. Our previous theoretical analysis with molecular-dynamics simulations helped to unveil the source of enhanced enantioselectivity: a relay mechanism that involves two of the six mutations was shown to induce strong cooperativity. In this investigation, single, double, and triple mutants were constructed and tested as enantioselective catalysts. This study supports our original postulate regarding the relay mechanism, offers further mechanistic insight into the role of individual mutations, and provides mutants that display even higher enantioselectivity (E of up to 64).

Catalysis↗

[The dynamic trends of biological evolution].

The available data on the thermodynamic stability of supramolecular biological structures and variations in the chemical composition of living organisms have allowed a macrothermodynamic model of biological evolution to be developed experimentally. In this model, the tendency toward a minimum of the specific Gibbs function of the formation of supramolecular structures of living organisms causes variations in the chemical composition and structure of living systems. It is shown that in the course of ontogenesis and phylogenesis, as well as long-lasting stages in the evolution of the organic world, the biosystems (as a result of the thermodynamic direction of evolutionary processes of the formation of supramolecular structures) are enriched with energy-intensive chemical substances, which displace water from these biosystems. The change in the composition and structure of biostructures of an adaptive character is also explained from the angle of macrothermodynamics.

Animals↗

A short introduction to the origin and molecular evolution of viruses.

The present review deals with conceptual and experimental approaches to two aspects of the origin and molecular evolution of viruses. In the section "Role of Retrons, Retroelements, and Reverse Transcriptase in the Evolution of Retroviruses and in Eukaryotic Genome Plasticity", Temin's concept that retrons are an ancient genetic element that during evolution of the species gave rise to retroviruses is presented. An opposing view of Xiong and Eickbush that the most probable ancestor of current retroelements is a retrotransposable element with gag- and pol-like genes is presented. Minus-strand RNA viruses are also discussed. The second aspect of this review is the molecular evolution of viruses at the level of the virus genome. Spiegelman's experiment on the evolution of self-replicating nucleic acid molecules outside living cells and Eigen's experimental and conceptual approaches to this subject are presented, along with studies on the evolutionary rates of base substitutions in viral RNA and defective molecules generated during replication.

Animals↗

The temporalis osteomuscular flap versus the free calvarial bone graft. An experimental study in the growing rabbit.

The authors have conducted an experimental study on the evolution of temporalis osteomuscular flaps compared with calvarial free bone grafts in young rabbits. The evaluation of the results has been performed with macroscopic, radiological and histological investigations in an early and late postoperative phase. This study has confirmed that the bone flaps remain viable and are characterized by a normal evolution. There is no evidence of anomaly of craniofacial growth nor asymmetry when compared with the contralateral side. On the other hand, the free bone grafts show the typical signs of necrosis and resorption. Some asymmetries are produced in comparison with the contralateral side, these being particularly evident in the two-months samples, while the overall craniofacial growth is not seriously impaired. This experimental study confirms the reliability of the temporalis osteomuscular flap in facial reconstruction.

Animals↗

Ion transport pathology in the mechanism of sickle cell dehydration.

Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leading from sickling-induced permeabilization of the red cell membrane to small cations, to the generation of the heterogeneity of age and hydration condition of circulating sickle cells. This review follows chronologically the major experimental findings and the evolution of guiding ideas for research in this field. Predictions derived from mathematical models of red cell and reticulocyte homeostasis led to the formulation of an alternative to prevailing gradualist views: a multitrack dehydration model based on interactive influences between the red cell anion exchanger and two K(+) transporters, the Gardos channel (hSK4, hIK1) and the K-Cl cotransporter (KCC), with differential effects dependent on red cell age and variability of KCC expression among reticulocytes. The experimental tests of the model predictions and the amply supportive results are discussed. The review concludes with a brief survey of the therapeutic strategies aimed at preventing sickle cell dehydration and with an analysis of the main open questions in the field.

Anemia, Sickle Cell↗

Description and interpretation of adaptive evolution of Escherichia coli K-12 MG1655 by using a genome-scale in silico metabolic model.

Genome-scale in silico metabolic networks of Escherichia coli have been reconstructed. By using a constraint-based in silico model of a reconstructed network, the range of phenotypes exhibited by E. coli under different growth conditions can be computed, and optimal growth phenotypes can be predicted. We hypothesized that the end point of adaptive evolution of E. coli could be accurately described a priori by our in silico model since adaptive evolution should lead to an optimal phenotype. Adaptive evolution of E. coli during prolonged exponential growth was performed with M9 minimal medium supplemented with 2 g of alpha-ketoglutarate per liter, 2 g of lactate per liter, or 2 g of pyruvate per liter at both 30 and 37 degrees C, which produced seven distinct strains. The growth rates, substrate uptake rates, oxygen uptake rates, by-product secretion patterns, and growth rates on alternative substrates were measured for each strain as a function of evolutionary time. Three major conclusions were drawn from the experimental results. First, adaptive evolution leads to a phenotype characterized by maximized growth rates that may not correspond to the highest biomass yield. Second, metabolic phenotypes resulting from adaptive evolution can be described and predicted computationally. Third, adaptive evolution on a single substrate leads to changes in growth characteristics on other substrates that could signify parallel or opposing growth objectives. Together, the results show that genome-scale in silico metabolic models can describe the end point of adaptive evolution a priori and can be used to gain insight into the adaptive evolutionary process for E. coli.

Adaptation, Physiological↗

[Cellular immunity in an experimental ascites tumor: tumor immunostimulation mediated by splenic lymphocytic cells].

The authors consider three successive phenomena in the experimental Ca H tumor evolution. A first stage of tumor resistance due to cytotoxic cells in the presence of some suppressor cells; a second stage when suppressor activity is predominantly observed, and a final stage of lymphocyte-mediated immunostimulation. Vasodilatation and angiogenesis are probably important during third stage.

Animals↗

The flowerpiercers' hook: an experimental test of an evolutionary trade-off.

The evolution of features that enhance an organism's performance in one activity can adversely affect its performance in another. We used an experimental approach to document a trade-off associated with the evolution of the long hook at the tip of the bill of birds belonging to the genus Diglossa (flowerpiercers). In Diglossa, the more derived flower-robbing nectarivorous species have maxillae (upper jaws) that terminate in enlarged curved hooks. The ancestral frugivorous species have maxillae with relatively small hooks. We mimicked bill evolution by clipping the terminal bill hook of nectarivorous Cinnamon-bellied Flowerpiercers (Diglossa baritula) to resemble the frugivorous condition. We found that birds with experimentally shortened bills ingested fruit more efficiently, but had a reduced ability to rob flowers. Birds with intact bills, by contrast, were good flower robbers but poor frugivores. The evolution of a hooked bill endowed flowerpiercers with the ability to efficiently pierce flowers and extract nectar, but hindered their efficiency to feed on fruit.

Adaptation, Physiological↗

Size scaling of mutation avalanches in a model for protein evolution.

The tunably rugged NK-model is used to study avalanche-like events that occur when environmental change causes fitness optima to disappear. The probability of an event with Delta substitutions scales as exp(-c Delta) for smooth landscapes, and as exp(-c Delta(2)) for rugged landscapes. Increasing the ruggedness leads to two competing effects: (1) more possible routes by which single mutations can increase the fitness, which dominates at low ruggedness and acts to increase Delta; and (2) a higher density of fitness optima, which dominates at high ruggedness and acts to decrease Delta. Due to these competing effects, the largest average values of Delta occur at intermediate ruggedness. The effects of system size on the avalanche events are examined, and average values of Delta increase logarithmically with system size. The variance to mean ratios for the number of substitutions per unit time are consistent with experimental results for protein evolution.

Animals↗