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PubMed1995

[Evolution of pharmaceutical provision in the National Health System (1984-1994)].

OBJECTIVES: To analyse the free pharmaceutical provision of the National Health Service, using the customary indicators. DESIGN: Longitudinal, retrospective and observational study, embracing the years 1984 to 1994. SETTING: The provision, using official National Health Service prescriptions, of pharmaceutical products via dispensaries. PARTICIPANTS: Prescriptions of the period under study. MEASUREMENTS AND MAIN RESULTS: The measurements for the evolutionary analysis of free pharmaceutical provision were carried out in absolute and relative values. Within the absolutes, public health expenditure on drugs went from 178,348 million pesetas in 1984 to 643,701 million in 1994; and prescriptions from 432 million in 1984 to 494 million in 1994. Beneficiaries' contributions for drugs, as a percentage of overall consumption, went down from 15.75% in 1984 to 9.16% in 1994. The indicators of pharmaceutical prescription placed the cost of sale to the public per prescription in 1994 at 1,446 pesetas, an increase of 195% over 1984, whereas the average expenditure per prescription (1,303 pesetas in 1994) went up by 215%. Expenditure per protected pensioner went from 18,180 pesetas in 1984 to 56,784 in 1994, with an average number of prescriptions per pensioner of 38.04. In this last year the tendency for consumption to fall, begun in 1993. The profiles of the therapeutical sub-groups, which were most consumed in cost terms, displayed large variations. CONCLUSIONS: The structural management measures adopted during the period under study, especially those for 1993 (new VAT on drugs, Royal Decree on Selective Financing of Medicines) and 1994 (average fall of 3% in the free sale price of drugs, collaboration of Dispensaries) are, in our view, those which have most affected the evolution of this free provision.

Insurance, Pharmaceutical Services↗
PubMedDate not supplied

[Malaria in Mayotte: past, present and future].

Discovered as a form of intermittent fevers in 1852 and confirmed by Blin in 1905, malaria has had a large impact on the mortality and the morbidity of the population living in Mayotte until 1976. An evolutionary analysis of the disease shows two distinct periods. The first period between 1792 and 1974 concerns the date of introduction of malaria to the island and the limited actions of the fight against malaria led by different organizations. The second period from 1976, when the program was established, to today could be entitled "18 years of fighting malaria in Mayotte". The second period has featured many events punctuated by two epidemics in 1984 and 1991. The results obtained in terms of the fight against malaria are characterized by a rapid fall of the transmission between 1976 and 1980, a resurgence of an epidemic in 1984, a cessation of the transmission in 1986, an explosive epidemic in 1991, and maintenance of the microcenters of epidemics since 1991 to today. They demonstrate the fragility of the conditions and prove that the ecosystem of Mayotte remains favorable to deterioration of the situation. These sero-epidemiological studies based on the estimation of the "geometrical rate of antibodies" allows for compensation of the techniques of parasitic evaluation when the index of malaria becomes very low. The principal vector Anopheles gambiae has adapted to the many varieties of natural habitats and to those of human origin due to environmental modification. Also the parasite, originating from the endemic residential zones, has been quasi-permanently introduced to the island. Thus, we are obliged to consolidate and diversify our means, notably towards a periodic evaluation of the phenomenon of in vivo resistance to chloroquine. This objective could be integrated within the framework of regional scientific cooperation. Moreover, the use of mosquito bed nets impregnated with pesticides is beginning to be the answer to the problem of people refusing to spray insecticide within their homes.

Comoros↗
PubMed1997

Acute phase proteins in salmonids: evolutionary analyses and acute phase response.

Inflammation induces dramatic changes in the biosynthetic profile of the liver, leading to increased serum concentrations of positive acute phase (AP) proteins and decreased concentrations of negative AP proteins. Serum amyloid A (SAA) and the pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are major AP proteins: their serum levels can rise by 1000-fold, indicating that they play a critical role in defense and/or the restoration of homeostasis. We have cloned SAA and a SAP-like pentraxin from salmonid fish species. The salmonid SAA shares approximately 70% amino acid identity with mammalian AP SAA. When salmonids are challenged with an AP stimulus, i.e., Aeromonas salmonicida, SAA responds dramatically as a major AP reactant. The salmonid pentraxin shows approximately 40% amino acid identity to both mammalian SAP and CRP. Evolutionary analysis suggests the presence of only a single such protein in teleosts and lower animal species. Surprisingly, the salmonid pentraxin behaves as a negative AP reactant, reminiscent of the SAP-like Syrian hamster female protein, in that hepatic mRNA concentrations decline to 50% of prestimulus levels. This study reinforces the hypothesis that SAA induction is an essential and universal feature of the vertebrate AP response and that it represents part of an ancient host defense system. Conversely, the species-dependent heterogeneity of pentraxin expression during the vertebrate AP response supports the possibility that its most important ancestral (and perhaps present) function is not related to its AP behavior.

Acute-Phase Proteins↗
PubMed1997

[Structural characteristics of four long terminal repeats (LTR) of human endogenous retroviruses and features of their integration sites].

Four LTR-containing regions of human chromosome 19 were sequenced by the primer walking technique using strings of short oligonucleotides tightly bound to the template. A comparative and evolutionary analysis of sequences homologous to human endogenous retroviruses (HERV) was performed, and the prototypes of the LTRs were determined. Analysis of the chromosome 19 sequences adjacent to LTR revealed that LTRs of HERV-K share a common location with other retroposons.

Base Sequence↗
PubMed1997

The crystallins: genes, proteins and diseases.

The crystallins were discovered as the structural proteins of the vertebrate eye lens in the last century by C.T. Mörner (Z. Physiol. Chem. 18, 1893, 61-106). Since that time the mammalian crystallins referred to as alpha-, beta-, and gamma-crystallins have been characterized with respect to their genetic organization, the regulation of their expression pattern and their participation in several diseases. Moreover, some crystallins have also been discovered outside the eye. Evolutionary analysis has demonstrated the relationship of crystallins to proteins involved in protection against stress. The alpha-crystallins are considered to be molecular chaperones and members of the small heat shock protein family; they have autokinase activity and are involved in the gamma-crystallin gene activation. The alpha-crystallins are associated with a broad variety of neurological disorders. The beta/gamma-crystallin superfamily is characterized by four greek key motifs. The various N- and C-terminal extensions of the beta/gamma-crystallins are mainly responsible for their distinct biophysical and biochemical properties. Modifications in the beta/gamma-crystallins or mutations in their genes lead to opacification of the eye lens (cataract). Other proteins found to be expressed at relatively high levels in the lens are characterized bytheir strong relationship to well-known enzymes. They are referred to as enzyme-crystallins, and as one example, the xi-crystallin will be discussed. It has evolved from a quinone oxidoreductase using a lens-specific promoter, and a mutation in xi-crystallin is involved in cataract formation.

Animals↗
PubMed1998

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China.

To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV) infection and the development of hepatocellular carcinoma (HCC) in H city, in the inshore area of the Yangtze River, where high prevalence of HCC has been reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV) markers, GBV-C/HGV-RNA and GBV-C/HGV E2 antibody (anti-HG E2) among 114 HCC patients and the same number of age- and sex-matched controls. There were no significant differences in the clinical and demographic characteristics between them, except for serum alanine aminotransferase level and history of liver diseases. There was a significant difference of hepatitis B virus surface antigen (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%; P<0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients, compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E2 were detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0 and 1.7% of the controls, respectively. Nucleotide sequences and molecular evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR) for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was 14.9, with a 95% CI of 4.9-45.4. HBsAg infection alone was 13.83 (95% CI 7.4-25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1-13.1), respectively. These data indicate that HBV infection is considered to be one of the major risk factors in patients with HCC and although GBV-C/HGV infection was observed in both the HCC and the control groups, it might not play an important role in the development of HCC in this area.

Adult↗
PubMed2005

Autonomous evolutionary algorithm in medical data analysis.

An autonomous evolutionary algorithm for constructing decision trees is presented. The algorithm requires no or minimal human interaction and shows some interesting properties when used on different medical datasets. The algorithm uses a non-standard implicit fitness evaluation in the selection phase of a co-evolving environment. Together with self-adaptation of evolution parameters and with some other improvements it can monitor and adjust its own behavior. The algorithm's capability to self-adapt to a given problem is used as a measure to predict if some dataset is just difficult or impossible to analyze. The autonomous algorithm on average produces very general solutions or gives no solution if the dataset is prone to the overfitting problem.

Algorithms↗
PubMed1990

Limitations of the evolutionary parsimony method of phylogenetic analysis.

Lake's evolutionary parsimony (EP) method of constructing a phylogenetic tree is primarily applied to four DNA sequences. In this method, three quantities--X, Y, and Z--that correspond to three possible unrooted trees are computed, and an invariance property of these quantities is used for choosing the best tree. However, Lake's method depends on a number of unrealistic assumptions. We therefore examined the theoretical basis of his method and reached the following conclusions: (1) When the rates of two transversional changes from a nucleotide are unequal, his invariance property breaks down. (2) Even if the rates of two transversional changes are equal, the invariance property requires some additional conditions. (3) When Kimura's two-parameter model of nucleotide substitution applies and the rate of nucleotide substitution varies greatly with branch, the EP method is generally better than the standard maximum-parsimony (MP) method in recovering the correct tree but is inferior to the neighbor-joining (NJ) and a few other distance matrix methods. (4) When the rate of nucleotide substitution is the same or nearly the same for all branches, the EP method is inferior to the MP method even if the proportion of transitional changes is high. (5) When Lake's assumptions fail, his chi2 test may identify an erroneous tree as the correct tree. This happens because the test is not for comparing different trees. (6) As long as a proper distance measure is used, the NJ method is better than the EP and MP methods whether there is a transition/transversion bias or whether there is variation in substitution rate among different nucleotide sites.

Base Sequence↗
PubMed2003

Evolutionary-based association analysis using haplotype data.

Association studies, both family-based and population-based, can be powerful means of detecting disease-liability alleles. To increase the information of the test, various researchers have proposed targeting haplotypes. The larger number of haplotypes, however, relative to alleles at individual loci, could decrease power because of the additional degrees of freedom required for the test. An optimal strategy would focus the test on particular haplotypes or groups of haplotypes, much as is done with cladistic-based association analysis. First suggested by Templeton et al. ([1987] Genetics 117:343-351), such analyses use the evolutionary relationships among haplotypes to produce a limited set of hypothesis tests and to increase the interpretability of these tests. To more fully utilize the information contained in the evolutionary relationships among haplotypes and in the sample, we propose generalized linear models (GLM) for the analysis of data from family-based and population-based studies. These models fully account for haplotype phase ambiguity and allow for covariates. The models are encoded into a software package (the Evolutionary-Based Haplotype Analysis Package, EHAP), which also provides for various kinds of exploratory data analysis. The exploratory analyses, such as error checking, estimation of haplotype frequencies, and tools for building cladograms, should facilitate the implementation of cladistic-based association analysis with haplotypes.

Genetic Predisposition to Disease↗
PubMedDate not supplied

Evolutionary and functional analysis of the tailless enhancer in Musca domestica and Drosophila melanogaster.

To further understand the evolutionary dynamics of the regulatory interactions underlying development, we expand on our previous analysis of hunchback and compare the structure and function of the tailless enhancer between Musca domestica and Drosophila melanogaster. Our analysis shows that although the expression patterns and functional protein domains of tll are conserved between Musca and Drosophila, the enhancer sequences are unalignable. Upon closer investigation, we find that these highly diverged enhancer sequences encode the same regulatory information necessary for Bicoid, Dorsal, and the terminal system to drive tll expression. The binding sites for these transcription factors differ in the sequence, number, spacing, and position between the Drosophila and Musca tll enhancers, and we were unable to establish homology between binding sites from each species. This implies that the Musca and Drosophila Bcd-binding sites have evolved de novo in the 100 million years since these species diverged. However, in transgenic Drosophila embryos the Musca tll enhancer is able to drive the same expression pattern as endogenous Drosophila tll. Therefore, during the rapid evolution of enhancer sequences individual binding sites are continually lost and gained, but the transcriptional output is maintained by compensatory mutations in cis and in trans.

Amino Acid Sequence↗
PubMed1999

Analysis of heregulin symmetry by weighted evolutionary tracing.

Heregulins are members of the protein family of EGF-like growth and differentiation factors. The primary cell-surface targets of heregulins are heterodimers of the EGF-receptor homolog HER2 with either HER3 or HER4. We used a weighted evolutionary trace analysis to identify structural features that distinguish the EGF-like domain (hrg) of heregulins from other members of the EGF family. In this analysis, each amino acid sequence is weighted according to its uniqueness and the variability in each position is assigned by an amino acid substitution matrix. Conserved residues in heregulin that are variable in other EGF-like domains are considered possible specificity-conferring residues. This analysis identifies two clusters of residues at the foot of the boot-shaped hrg domain. The residues in one cluster are recruited from the N-terminus; those in the other are from the ohm-loop region and show a weak sequence similarity to the N-terminal residues at the opposite side of the boot. The remaining residues with high conservation scores distribute themselves into these two distinct surfaces on hrg. This pseudo-twofold symmetry and the presence of two distinct interfaces may reflect the preference of hrg for heterodimeric versus homodimeric HER complexes.

Amino Acid Sequence↗
PubMed2003

Inference of Euler angles for single-particle analysis by means of evolutionary algorithms.

Single-particle analysis is one of the methods for structural studies of protein and macromolecules; it requires advanced image analysis of electron micrographics. Reconstructing three-dimensional (3D) structure from microscope images is not an easy analysis because of the low image resolution of images and lack of the directional information of images in 3D structure. To improve the resolution, different projections are aligned, classified, and averaged. Inferring the orientations of these images is so difficult that the task of reconstructing 3D structures depends upon the experience of researchers. But recently, a method to reconstruct 3D structures was automatically devised. In this paper, we propose a new method for determining Euler angles of projections by applying genetic algorithms. We empirically show that the proposed approach has improved the previous one in terms of computational time and acquired precision.

Algorithms↗
PubMed1998

On the best evolutionary rate for phylogenetic analysis.

The effect of the evolutionary rate of a gene on the accuracy of phylogeny reconstruction was examined by computer stimulation. The evolutionary rate is measured by the tree length, that is, the expected total number of nucleotide substitutions per site on the phylogeny. DNA sequence data were simulated using both fixed trees with specified branch lengths and random trees with branch lengths generated from a model of cladogenesis. The parsimony and likelihood methods were used for phylogeny reconstruction, and the proportion of correctly recovered branch partitions by each method was estimated. Phylogenetic methods including parsimony appear quite tolerant of multiple substitutions at the same site. The optimum levels of sequence divergence were even higher than upper limits previously suggested for saturation of substitutions, indicating that the problem of saturation may have been exaggerated. Instead, the lack of information at low levels of divergence should be seriously considered in evaluation of a gene's phylogenetic utility, especially when the gene sequence is short. The performance of parsimony, relative to that of likelihood, does not necessarily decrease with the increase of the evolutionary rate.

Biological Evolution↗
PubMed1994

The primary structure of sheep liver cytosolic serine hydroxymethyltransferase and an analysis of the evolutionary relationships among serine hydroxymethyltransferases.

The complete amino-acid sequence of sheep liver cytosolic serine hydroxymethyltransferase was determined from an analysis of tryptic, chymotryptic, CNBr and hydroxylamine peptides. Each subunit of sheep liver serine hydroxymethyltransferase consisted of 483 amino-acid residues. A comparison of this sequence with 8 other serine hydroxymethyltransferases revealed that a possible gene duplication event could have occurred after the divergence of animals and fungi. This analysis also showed independent duplication of SHMT genes in Neurospora crassa. At the secondary structural level, all the serine hydroxymethyltransferases belong to the alpha/beta category of proteins. The predicted secondary structure of sheep liver serine hydroxymethyltransferase was similar to that of the observed structure of tryptophan synthase, another pyridoxal 5'-phosphate containing enzyme, suggesting that sheep liver serine hydroxymethyltransferase might have a similar pyridoxal 5'-phosphate binding domain. In addition, a conserved glycine rich region, G L Q G G P, was identified in all the serine hydroxymethyltransferases and could be important in pyridoxal 5'-phosphate binding. A comparison of the cytosolic serine hydroxymethyltransferases from rabbit and sheep liver with other proteins sequenced from both these sources showed that serine hydroxymethyltransferase was a highly conserved protein. It was slightly less conserved than cytochrome c but better conserved than myoglobin, both of which are well known evolutionary markers. C67 and C203 were specifically protected by pyridoxal 5'-phosphate against modification with [14C]iodoacetic acid, while C247 and C261 were buried in the native serine hydroxymethyltransferase. However, the cysteines are not conserved among the various serine hydroxymethyltransferases. The exact role of the cysteines in the reaction catalyzed by serine hydroxymethyltransferase remains to be elucidated.

Amino Acid Sequence↗
PubMed1999

Evolutionary dynamics of Ty1-copia group retrotransposons in grass shown by reverse transcriptase domain analysis.

The evolutionary dynamics of Ty1-copia group retrotransposons in grass were examined by reverse transcriptase (RT) domain analysis. Twenty-three rice RT sequences were newly determined for this report. Phylogenetic analysis of 177 RT sequences, mostly derived from wheat, rice, and, maize, showed four distinct families, which were designated G1, G2, G3, and G4. Three of these families have elements obtained from distantly related species, indicative of origins prior to the radiation of grass species. Results of Southern hybridization and detailed comparisons between the wheat and rice sequences indicated that each of the families had undergone a distinct pattern of evolution. Multiple families appear to have evolved in parallel in a host species. Analyses of synonymous and nonsynonymous substitutions suggested that there is a low percentage of elements carrying functional RT domains in the G4 family, indicating that the production of new G4 elements has been controlled by a small number of elements carrying functional RT domains.

Evolution, Molecular↗
PubMed2006

CGAT: a comparative genome analysis tool for visualizing alignments in the analysis of complex evolutionary changes between closely related genomes.

BACKGROUND: The recent accumulation of closely related genomic sequences provides a valuable resource for the elucidation of the evolutionary histories of various organisms. However, although numerous alignment calculation and visualization tools have been developed to date, the analysis of complex genomic changes, such as large insertions, deletions, inversions, translocations and duplications, still presents certain difficulties. RESULTS: We have developed a comparative genome analysis tool, named CGAT, which allows detailed comparisons of closely related bacteria-sized genomes mainly through visualizing middle-to-large-scale changes to infer underlying mechanisms. CGAT displays precomputed pairwise genome alignments on both dotplot and alignment viewers with scrolling and zooming functions, and allows users to move along the pre-identified orthologous alignments. Users can place several types of information on this alignment, such as the presence of tandem repeats or interspersed repetitive sequences and changes in G+C contents or codon usage bias, thereby facilitating the interpretation of the observed genomic changes. In addition to displaying precomputed alignments, the viewer can dynamically calculate the alignments between specified regions; this feature is especially useful for examining the alignment boundaries, as these boundaries are often obscure and can vary between programs. Besides the alignment browser functionalities, CGAT also contains an alignment data construction module, which contains various procedures that are commonly used for pre- and post-processing for large-scale alignment calculation, such as the split-and-merge protocol for calculating long alignments, chaining adjacent alignments, and ortholog identification. Indeed, CGAT provides a general framework for the calculation of genome-scale alignments using various existing programs as alignment engines, which allows users to compare the outputs of different alignment programs. Earlier versions of this program have been used successfully in our research to infer the evolutionary history of apparently complex genome changes between closely related eubacteria and archaea. CONCLUSION: CGAT is a practical tool for analyzing complex genomic changes between closely related genomes using existing alignment programs and other sequence analysis tools combined with extensive manual inspection.

Algorithms↗
PubMed1989

Kinetochore size variation in mammalian chromosomes: an image analysis study with evolutionary implications.

The kinetochore, a proteinaceous plate that is the site for attachment of spindle microtubules to the metaphase chromosome, can be visualized using anti-kinetochore indirect immunofluorescence. We have used computer-assisted image analysis to measure the variation of kinetochore surface areas, as reflected by immunofluorescence areas, in cell lines derived from rat kangaroo, Chinese hamster and common rat, to determine if our size estimates correlate well with those obtained using measurements from electron micrographs. In addition, we used male and female human fibroblast cell lines, as well as a transformed human female cell line as well as a transformed human female cell line (HeLa), to examine kinetochore size variation among cells, between sexes, and between cell lines. We found that our system gave reproducible estimates of kinetochore size, and that these sizes correlated very well (r = 0.95) with the electron micrograph measurements. In examining variation within humans, we observed measurable differences between cell lines. Despite this difference, all the human lines had size distributions that were leptokurtotic and positively skewed. The fact that very few chromosomes exhibited areas smaller than the mode gives support to the idea that mammalian chromosomes may require a specific, minimum amount of kinetochore material in order to maintain stable attachment to the mitotic spindle. On the other hand, the positive skewness seems to indicate that larger kinetochores, possibly the result of events such as Robertsonian fusions, are fully functional. The retention of this plasticity may allow the chromosomes to maintain an evolutionary adaptability that might otherwise be lost.

Animals↗