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PubMed2000

RELIEF study: first consolidated European data. Reflux assEssment and quaLity of lIfe improvement with micronized Flavonoids.

The RELIEF study (Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [CVI]) is a prospective, controlled, multicenter, international study performed in patients with or without venous reflux. This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI. The European countries, the subject of this report, were represented by the Czech and Slovak Republics, Hungary, Poland, Russia, and Spain. The principal aims of the study were: 1. To validate the first quality-of-life scale specific to chronic venous insufficiency (CMVIQ) in different languages and to assess the evolution of quality of life in patients suffering from CVI, with or without venous reflux, treated with micronized purified flavonoid fraction (MPFF*) (1,000 mg/day). 2. To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography. 3. To assess the evolution of symptoms and signs with a specific emphasis on edema through validated Leg-O-Meter measurement (heaviness, pain, cramps, sensation of swelling, edema) in patients suffering from CVI and treated with MPFF, 1,000 mg/day, during 6 months. The first country-by-country statistical analysis and the European consolidated analysis are now available. The CIVIQ questionnaires adapted to each participating country have been validated with highly significant validity and reproducibility (p<0.0001). All dimensions have demonstrated a highly significant and evolving improvement during the study. The results show several interesting findings concerning the epidemiologic data and, of these, two were particularly interesting: - More than 50% of patients suffering from CVI (class 0 to 4 of the CEAP classification) were reflux-free, which means that they were suffering from functional CVI. Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months' treatment with MPFF; the number of patients in the more severe classes decreased to the benefit of the less severe classes. Symptoms such as pain, leg heaviness, sensation of swelling, and cramps were significantly improved (p=0.0001). This was associated with a significant decrease in edema, when present, measured by leg circumferences with the Leg-O-Meter (p=0.0001). In conclusion, the European results of the RELIEF study showed the perfect validity and reproducibility of CIVIQ questionnaire adaptations, and the positive progression of quality-of-life scores on MPFF treatment. This progression was paralleled by clinical improvement of patients reflected not only by assessment of CVI symptoms and signs but also by evolution of the CEAP classification.

Cardiovascular Agents↗

PubMed2004

Structure and function of neurons in the complex of the nucleus electrosensorius of Sternopygus and Eigenmannia: diencephalic substrates for the evolution of the jamming avoidance response.

The ability to discriminate the sign of the difference in frequency (DF) between two wavelike signals is integral to the jamming avoidance response (JAR) of weakly electric gymnotiform fish such as Eigenmannia. 'Whole-cell' intracellular recordings from neurons in the nucleus electrosensorius (nE) of Sternopygus, a gymnotiform that lacks the JAR, revealed that this nucleus receives information from both the ampullary and the tuberous electrosensory systems. Most tuberous units responded to DF stimuli, and many of these cells were DF sign-sensitive, i.e., they responded differently for one sign of DF. Although the distribution of ampullary units was somewhat restricted, sign-sensitive units were found in all areas of the nE in Sternopygus. Whole-cell recordings made in the nE of Eigenmannia revealed that, as in Sternopygus, sign-sensitive cells were not restricted to areas associated with control of the JAR. The diverse neurophysiology and connectivity of the nucleus electrosensorius suggests that, besides its role in the JAR of some members of the order, this nucleus likely serves as an interface between sensory input and neural circuits controlling other behaviors and endocrinological states in other gymnotiforms as well. The discovery of sign sensitivity in the nE of Sternopygus indicates that this property is not uniquely associated with the presence of a JAR; rather, the ability to discriminate the sign of DF may be relevant to many other behavioral contexts in gymnotiforms. Existing evidence indicates that the JAR evolved more than once in this group; the presence of sign sensitivity in ancestral gymnotiforms may have made this parallelism more likely.

Animals↗

PubMed2004

Ancestral gene fusion in cellobiose dehydrogenases reflects a specific evolution of GMC oxidoreductases in fungi.

Cellobiose dehydrogenases (CDHs) are extracellular hemoflavoenzymes that are thought to be involved in the degradation of two of the most abundant biopolymers in the biosphere, cellulose and lignin. To date, these enzymes, consisting of a cytochrome domain and a flavin domain, have been detected and sequenced exclusively in the kingdom of fungi. Independent phylogenetic analyses of two distinct domains of CDH genes reveal that they evolved in parallel as fused genes. Whereas the cytochrome domains are unique sequence motifs, the flavin domains clearly belong to the glucose-methanol-choline (GMC) oxidoreductase family--an evolution line of widespread flavoproteins extending from the Archae to higher eukaryotes. The most probable unrooted phylogenetic tree obtained from our analysis of 52 selected GMC members reveals five principal evolutionary branches: cellobiose dehydrogenase, cholesterol oxidase (COX), hydroxynitrile lyase, alcohol oxidase (AOX)/glucose oxidase (GOX)/choline dehydrogenase, and a branch of dehydrogenases with various specificities containing also an Archaeon open reading frame (ORF). Cellobiose dehydrogenases cluster with cholesterol oxidases and the clade of various specificities, whereas hydroxynitrile lyases are closely related to glucose oxidases, alcohol oxidases, and choline dehydrogenases. The results indicate that the evolutionary line from a primordial GMC flavoprotein to extant cellobiose dehydrogenases was augmented after an early acquisition of the cytochrome domain to form two distinct branches for basidiomycetes and ascomycetes. One ascomycetous evolutionary line of CDHs has acquired a carbohydrate-binding module (CBM) of type 1, the sequence of which is similar to that of corresponding domains in several glycosidases. This is the first attempt towards a comprehensive phylogenetic analysis of cellobiose dehydrogenases.

Alcohol Oxidoreductases↗

PubMed1990

The general stochastic model of nucleotide substitution.

DNA sequence evolution through nucleotide substitution may be assimilated to a stationary Markov process. The fundamental equations of the general model, with 12 independent substitution parameters, are used to obtain a formula which corrects the effect of multiple and parallel substitutions on the measure of evolutionary divergence between two homologous sequences. We show that only reversible models, with six independent parameters, allow the calculation of the substitution rates. Simulation experiments on DNA sequence evolution through nucleotide substitution call into question the effectiveness of the general model (and of any other more detailed description); nevertheless, the general model results are slightly superior to any of its particular cases.

Animals↗

PubMed2000

Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity.

Carcinosarcomas of the uterus, ovaries, and fallopian tubes are highly aggressive neoplasms with incompletely understood histogenesis. Although recent immunohistochemical, cell culture, and molecular genetic studies all favor these cancers to be monoclonal in origin, the extent of intratumoral genetic heterogeneity in these tumors with divergent histology has not been reported previously. For this study, we microdissected a total of 172 carcinomatous or sarcomatous foci from 17 gynecological carcinosarcomas and analyzed allelic status with 41 microsatellite markers on chromosomal arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11p, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. With the exception of a single case with microsatellite instability, we found shared allelic losses and retentions among multiple individually dissected foci of each case, strongly supportive of the concept of a monoclonal origin for these neoplasms. In eight of these cases, we also found heterogeneous patterns of allelic loss at limited numbers of chromosomal loci in either the carcinomatous or sarcomatous components of the neoplasms. These heterogeneous patterns of allelic losses were consistent with either genetic progression or genetic diversion occurring during the clonal evolution of these neoplasms. In two cases, we found the specific patterns of genetic progression to be consistent with sarcomatous components of the neoplasms arising from carcinomatous components. We conclude that most of the gynecological carcinosarcomas have a monoclonal origin, and that genetic progression and diversion parallel the development of divergent phenotypes in these tumors. Because phenotypically divergent areas of the tumors share numerous genetic alterations, this divergence most likely occurs relatively late in the evolution of these tumors.

Carcinosarcoma↗

PubMedDate not supplied

The evolution of the millennium bug.

How could mankind, knowing the year 2000 would inevitably arrive, manoeuvre into worldwide technical problems because of a little computer bug? Two major parallels can be drawn to biological systems, and both are based on evolutionary principles. First, any new steps in development are founded on building blocks invented earlier. Basic building blocks are hardly changed anymore because further developments depend on their function. Second, imperfections of such building blocks are irrelevant as long as no corresponding selection pressure exists. If a time-coded computer bug occurs sufficiently early during technological development it can become part of innumerous hard-wired or soft-coded programs and devices without ever attracting attention. However, the arrival of a certain data can instantly put a high selection pressure upon it. This behaviour can be understood as a direct consequence of the autonomous dynamics that the development of complex systems implicates.

Animals↗

PubMed2006

No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation.

BACKGROUND: The mitochondrial DNA (mtDNA) of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin), by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans) known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea). RESULTS: The mtDNA surveyed (630 bp of cytochrome oxidase subunit I) was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years) is similar to that in most plants, but 50-100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. CONCLUSION: Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes.

Animals↗

PubMed1994

Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix.

Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

Animals↗

PubMed1994

Evolutionary expansion of the Monogenea.

The evolutionary expansion of the monogeneans has taken place in parallel with the diversification of the fish-like vertebrates. In this article the main trends in monogenean evolution are traced from a hypothetical skin-parasitic ancestor on early vertebrates. Special consideration is given to the following topics: early divergence between skin feeders and blood feeders; diversification and specialization of the haptor for attachment to skin; transfer from host to host, viviparity and the success of the gyrodactylids; predation on skin parasites and camouflage; colonization of the buccal and branchial cavities; diversification and specialization of the haptor for attachment to the gills; phoresy in gill parasites; the development of endoparasitism and the origin of the cestodes; the success of dactylogyroidean gill parasites; the uniqueness of the polyopisthocotyleans; ovoviviparity and the colonization of the tetrapods. Host specificity has been the guiding force of coevolution between monogeneans and their vertebrate hosts, but the establishment of monogeneans on unrelated hosts sharing the same environment (host-switching) may have been underestimated. Host-switching has provided significant opportunities for evolutionary change of direction and is probably responsible for the establishment of monogeneans on cephalopod molluscs, on the hippopotamus and possibly on chelonians. There are indications that host-switching may be more common in monogeneans that spread by direct transfer of adults/juveniles from host to host. A limitation on the further expansion of monogeneans is the need for water for the dispersal of the infective larva (oncomiracidium).

Animals↗

PubMed1990

Mathematical modeling of the excitation process in myocardial tissue: influence of fiber rotation on wavefront propagation and potential field.

In our macroscopic model the heart tissue is represented as a bidomain coupling the intra- and extracellular media. Owing to the fiber structure of the myocardium, these media are anisotropic, and their conductivity tensors have a principal axis parallel to the local fiber direction. A reaction-diffusion system is derived that governs the distribution and evolution of the extracellular and transmembrane potentials during the depolarization phase of the heart beat. To investigate frontlike solutions, the system is rescaled and transformed into a system dependent on a small parameter. Subsequently a perturbation analysis is carried out that yields zero- and first-order approximations called eikonal equations. The effects of the transmural fiber rotation on wavefront propagation and the corresponding potential field, elicited by point stimulations, are investigated by means of numerical simulations.

Animals↗

PubMed1991

PCR technique as an alternative method for diagnosis and molecular epidemiology of rabies virus.

We have investigated the PCR amplification technique of viral nucleic acids as an alternative protocol for diagnosis and epidemiological studies of rabies virus. A primer set mapping in the nucleoprotein cistron allowed a specific and sensitive amplification of infected brain material, fulfilling the diagnosis requirements. One hundred samples checked by Southern or dot-blot analysis using both radioactive and non-radioactive probes showed identical results in parallel with routine techniques. For molecular epidemiological studies we selected another set of conserved primers flanking the highly evolutive pseudogene (psi gene) region. This set was found to be efficient for all tested fixed rabies virus strains or wild rabies virus isolates as well as the rabies-related Mokola virus. We describe a progressive characterization of the strain that could be extended from rapid typing by a limited panel of restriction enzymes, to the ultimate identification of the nucleotide sequence by an original direct sequencing technique of amplified segments.

Animals↗

PubMed2005

Effect of sol-gel transition on shear-induced drop deformation in aqueous mixtures of gellan and kappa-carrageenan.

In this work, we present an experimental methodology to investigate the dynamics under shear flow of a drop that is gelling as a consequence of a temperature quench. The experiments were carried out on the system water/gellan/kappa-carrageenan in the biphasic region of the phase diagram, the gellan-rich phase being used as the dispersed phase. Gelation was brought about by lowering the temperature during flow after steady state drop deformation had been reached. Simple shear flow was applied by using a parallel plate apparatus equipped with optical microscopy and image analysis, which made it possible to monitor drop shape evolution before, during, and after gelation. The onset of gelation trapped drop deformation, thus producing anisotropic particles. The fingerprint of gelation was the simultaneous tumbling of the drops, which rotated as rigid ellipsoids under the action of shear flow. Interfacial tension between the two equilibrium phases was determined at different times during the temperature quench by analyzing drop retraction upon cessation of flow. Up to gelation, no significant change was observed in the measured values.

Journal Article↗

PubMedDate not supplied

Three-dimensional spatial variability of chemical properties around a monitored waste emplacement tunnel.

Regulatory requirements and scientific needs require that the response of the geological system to emplacement of high level radioactive waste be monitored for long time periods. This monitoring activity is intended to establish the extent to which predicted behavior matches the actual response of the geological system to waste emplacement. To accomplish this goal, field measurements must be made at a spatial resolution that will determine whether the changes in parameters that are monitored conform to predicted evolutionary patterns. From the perspective of thermohydrological and geochemical parameters, key measurements will consider pore water compositional evolution and changes in matrix and fracture saturation in the near vicinity of waste emplacement tunnels. A massively parallel high performance computational platform (a 1200 processor IBM SP-2) was used to conduct three-dimensional, high resolution simulations to ascertain the spatial variability to be expected during a monitoring period. The results show that spatial variability in certain chemical parameters below waste emplacement tunnels provides robust targets for monitoring, but will require sampling on the scale of 10 s of centimeters in some locations, in order to rigorously test models. Chemical variability induced by relatively small changes in waste package heat output suggests that designing a monitoring program that will rigorously test model predictions will likely require high resolution, three-dimensional simulations of the "as-built" monitoring tunnels.

Environmental Monitoring↗

PubMed1999

The RAG1/RAG2 complex constitutes a 3' flap endonuclease: implications for junctional diversity in V(D)J and transpositional recombination.

During V(D)J recombination, processing of branched coding end intermediates is essential for generating junctional diversity. Here, we report that the RAG1/ RAG2 recombinase is a 3' flap endonuclease. Substrates of this nuclease activity include various coding end intermediates, suggesting a direct role for RAG1/ RAG2 in generating junctional diversity during V(D)J recombination. Evidence is also provided indicating that site-specific RSS nicking involves RAG1/RAG2-mediated processing of a localized flap-like structure, implying 3' flap nicking in multiple DNA processing reactions. We have also demonstrated that the bacterial transposase Tn10 contains a 3' flap endonuclease activity, suggesting a mechanistic parallel between RAG1/RAG2 and other transposases. Based on these data, we propose that numerous transposases may facilitate genomic evolution by removing single-stranded extensions during the processing of excision site junctions.

Animals↗

PubMed2002

To err and win a nobel prize: Paul Boyer, ATP synthase and the emergence of bioenergetics.

Paul Boyer shared a Nobel Prize in 1997 for his work on the mechanism of ATP synthase. His earlier work, though (which contributed indirectly to his triumph), included major errors, both experimental and theoretical. Two benchmark cases offer insight into how scientists err and how they deal with error. Boyer's work also parallels and illustrates the emergence of bioenergetics in the second half of the twentieth century, rivaling achievements in evolution and molecular biology.

ATP Synthetase Complexes↗

PubMed1995

The evolution of emergent computation.

A simple evolutionary process can discover sophisticated methods for emergent information processing in decentralized spatially extended systems. The mechanisms underlying the resulting emergent computation are explicated by a technique for analyzing particle-based logic embedded in pattern-forming systems. Understanding how globally coordinated computation can emerge in evolution is relevant both for the scientific understanding of natural information processing and for engineering new forms of parallel computing systems.

Journal Article↗

PubMed2002

Short inversions and conserved gene cluster.

MOTIVATION: Two independent sets of recent observations on newly sequenced microbial genomes pertain to the prevalence of short inversion as a gene order rearrangement process and to the lack of conservation of gene order within conserved gene clusters. We propose a model of inversion where the key parameter is the length of the inverted fragment. RESULTS: We show that there is a qualitative difference in the pattern of evolution when the inversion length is small with respect to the cluster size and when it is large. This suggests an explanation of the lack of parallel gene order in conserved clusters and raises questions about the statistical validity of putative functionally selected gene clusters if these have only been tested against inappropriate null hypotheses.

Base Sequence↗

PubMed2006

Structure of nematic liquid crystalline elastomers under uniaxial deformation.

We have used in situ x-ray diffraction and calorimetry to study liquid crystalline elastomers prepared using a one-step photopolymerization method. We used suspended weights to stretch free-standing crystalline elastomer films. With the mechanical stress parallel to the initial director, we observed a gradual nematic to isotropic transition with increasing temperature. The thermal evolution of the nematic order parameter on cooling, together with the observation of isotropic-nematic coexistence over a broad temperature range, suggests that the heterogeneity in the samples introduces a distribution of transition temperatures. With the mechanical stress perpendicular to the initial director, we observed both uniform director rotation and stripe formation, depending on the details of sample preparation.

Journal Article↗