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PubMed1994

Horizontal gene transfer in the evolution of group A streptococcal emm-like genes: gene mosaics and variation in Vir regulons.

Most M type 5 group A streptococcal strains were found to contain a single emm-like gene between virR and scpA (the Vir regulon), but two distinct emm-like genes were identified in the Vir regulon of the M5 strain NCTC8193. The complete sequences of both of these genes were determined. One, called emm5.8193, was shown to be a minor variant of the previously described emm5 gene from strain Manfredo. The second, designated enn5.8193, expresses an IgG-binding protein when cloned in Escherichia coli. A comparison of enn5.8193 with emm-like gene sequences from other strains indicated that it has a mosaic structure, consisting of distinct segments originating from emm-like genes in different OF+ and OF- strains. These data provide the first clear evidence that the horizontal transfer of emm-like sequences between distinct strains contributes to the evolution of group A streptococcal emm-like genes and Vir regulons.

Bacterial Proteins↗
PubMed2005

Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial.

OBJECTIVE: To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. SUMMARY BACKGROUND DATA: Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia. PATIENTS AND METHODS: Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded. RESULTS: No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity. CONCLUSIONS: Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.

Aged↗
PubMed2004

Phylogeny of the Baldratiina (Diptera: Cecidomyiidae) inferred from morphological, ecological and molecular data sources, and evolutionary patterns in plant-galler relationships.

The phylogeny of the gall-midge subtribe Baldratiina (Diptera: Cecidomyiidae) was reconstructed from molecular (partial sequence of the mitochondrial 12S rDNA), morphological and ecological data sets, using 16 representative species of most of the genera. The morphological and ecological data were combined in a single character matrix and analyzed separately from the molecular data, resulting in an eco-morphological cladogram and a molecular cladogram. Attributes of galls and host associations were superimposed on the molecular cladogram in order to detect possible trends in the evolution of these traits. The cladograms resulting from the two independent analyses were statistically incongruent, although both provide evidence for the monophyly of the genera Baldratia and Careopalpis and the paraphyly of the genera Stefaniola and Izeniola. The results suggest a minor impact of the morphological characters traditionally used in the classification of the Baldratiina, whereas ecological data had a major impact on the phylogenetic inference. Mapping of gall and host attributes on the molecular cladogram suggests that multi-chambered stem galls constitute the ancestral state in the subtribe, with several subsequent shifts to leaf galls. It is concluded that in contrast to other studied groups of gall insects, related baldratiine species induce different types of galls, attesting to speciation driven by gall-type shifts at least as often as host shifts.

Animals↗
PubMed2001

Population genetic analysis of the protease locus of human immunodeficiency virus type 1 quasispecies undergoing drug selection, using a denaturing gradient-heteroduplex tracking assay.

Monitoring the evolution of human immunodeficiency virus type 1 (HIV-1) drug resistance requires measuring the frequency of closely related genetic variants making up the complex viral quasispecies found in vivo. In order to resolve both major and minor (>/=2%) protease gene variants differing by one or more nucleotide substitutions, we analyzed PCR products derived from plasma viral quasispecies by using a combination of denaturing gradient gel electrophoresis and DNA heteroduplex tracking assays. Correct population sampling of the high level of genetic diversity present within viral quasispecies could be documented by parallel analysis of duplicate, independently generated PCR products. The composition of genetically complex protease gene quasispecies remained constant over short periods of time in the absence of treatment and while plasma viremia fell >100-fold following the initiation of protease inhibitor ritonavir monotherapy. Within a month of initiating therapy, a strong reduction in the genetic diversity of plasma viral populations at the selected protease locus was associated with rising plasma viremia and the emergence of drug resistance. The high levels of protease genetic diversity seen before treatment reemerged only months later. In one patient, reduction in genetic diversity at the protease gene was observed concomitantly with an increase in diversity at the envelope gene (E. L. Delwart, P. Heng, A. Neumann, and M. Markowitz, J. Virol. 72:2416-2421, 1998), indicating that opposite population genetic changes can take place in different HIV-1 loci. The rapid emergence of drug-resistant HIV-1 was therefore associated with a strong, although only transient, reduction in genetic diversity at the selected locus. The denaturing gradient-heteroduplex tracking assay is a simple method for the separation and quantitation of very closely related, low-frequency, genetic variants within complex viral populations.

Biological Evolution↗
PubMed2000

Evidence for transcortical reflex pathways in the lower limb of man.

The existence of transcortical reflex pathways in the control of distal arm and hand muscles in man is now widely accepted. Much more controversy exists regarding a possible contribution of such reflexes to the control of leg muscles. It is often assumed that transcortical reflex pathways play no, or only a minor, role in the control of leg muscles. Transcortical reflex pathways according to this view are reserved for the control of the distal upper limb and are seen in close relation to the evolution of the primate hand. Here we review data, which provide evidence that transcortical reflexes do exist for lower limb muscles and may play a significant role in the control of at least some of these muscles. This evidence is based on animal research, recent experiments combining transcranial magnetic stimulation with peripheral electrical and mechanical stimulation in healthy subjects and neurological patients. We propose that afferent activity from muscle and skin may play a role in the regulation of bipedal gait through transcortical pathways.

Animals↗
PubMed1986

Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee.

A 4 month old child was immunized with a vaccine containing the Sabin live attenuated vaccine strains of all three serotypes of poliovirus. The antigenic and molecular evolution of the Sabin strain of poliovirus type 3 was then followed throughout the entire period of virus excretion. Novel strains appeared at 8, 42 and 52 days post-vaccination and were the products of both intertypic recombination between type 2 and type 3 poliovirus in regions of the genome coding for non-structural proteins and of point mutations in the region coding for the structural proteins. Excretion of virus continued for 73 days. All strains examined reacted with all monoclonal antibodies specific for the main immunodominant antigenic site of type 3 poliovirus, but variation was observed at other, immunorecessive sites. These findings have possible implications for the evolution of the virus in vaccinees or in epidemics and are consistent with the known antigenic stability of the virus.

Antibodies, Monoclonal↗
PubMed1997

Re-evaluation of oral contraceptive classifications.

Classification of combination oral contraceptives (OCs) by "generation"--typically based on the time of introduction of new compounds--is problematic. The estrogen and progestin components may be present in differing doses, and their interaction may therefore vary from one formulation to another. In addition, assigning the progestin component itself to a particular generation does not account for the unique characteristics of individual progestins within that group. These issues can be clarified by understanding the evolution of combination OCs in relation to dosage changes and by differentiating the pharmacologic profiles of individual progestins, particularly norgestimate, desogestrel, and gestodene. Although all sex steroids have the same basic structure, relatively minor structural modifications can cause dramatic alterations in biochemical activity. Progestational activity is the desired pharmacologic effect of progestins used in OCs, whereas androgenic activity, which increases the potential for adverse metabolic and physical side effects, is undesired. In vitro assays of the ability of various OC progestins to bind progestin and androgen receptors suggest that the androgen/progestin (A/P) binding ratio--a measure of progestin selectivity--is more favorable for norgestimate than for levonorgestrel, gestodene, or desogestrel. In vivo measurements of interactions between various progestins and human sex hormone binding globulin (SHBG) support the concept that generational classification of OC progestins is misleading. These compounds also differ clinically, as exemplified by differential effects on lipoprotein metabolism. In summary, progestins exhibit individually unique biochemical and clinical properties.

Animals↗
PubMed2002

Evolution and virulence of serogroup 6 pneumococci on a global scale.

To study the evolution and virulence of pneumococcal populations, we used multilocus sequence typing to identify the major clones among 212 carriage and invasive isolates expressing capsular serogroup 6 from 39 countries. The global population consisted of 8 major complexes and 6 minor complexes of related clones and 32 clones of diverse origin. Surprisingly, serotype 6A clones evolved by mutation nearly as often as by recombination, whereas serotype 6B clones evolved almost exclusively by recombination (P = 0.0029). This is the first report of population genetic differences among serotypes of this species. The largest clonal complex was associated with invasive disease (P = 0.019) and included a common ancestor for five previously identified drug-resistant clones. The putative ancestors of the major clonal complexes were represented by a greater proportion of carriage isolates than were their descendents (P = 0.001), and the ancestors tended to be less virulent than their descendents in a mouse model of infection. These data suggested that virulent serogroup 6 clones have evolved multiple times from less-virulent ancestral clones.

Adolescent↗
PubMed1979

Evolutionary potential: a mathematical hypothesis of mouse hemoglobin beta chain evolution.

This paper examines the possibility that the linkage arrangements and regulatory properties of genes may be influenced by selection. A mathematical hypothesis is developed in order to show how selective properties of hemoglobin beta chains could have influenced the linkage and regulation of their structural genes. The hypothesis is applied to the case of mouse hemoglobin beta chains. In most mice, closely-linked pairs of loci (doublets) code for two structurally divergent beta chains in unequal amounts. Some mouse strains have singlet alleles, however, coding for another beta chain variant. With the mathematical hypothesis, one can show that selectively determined "evolutionary potentials" may have favored changes in proportions of major and minor chains produced by a doublet allele. In the extreme case, zero production of the minor chain may give a selective advantage, leading to a singlet; conversely, selection may favor linking another gene to the singlet locus to give a doublet. A specific prediction of the model is the stable maintenance under certain conditions of multiple alleles at regulatory loci. The concept of evolutionary potential thus suggests that selection could have influenced the evolution of genotypic fitnesses, in addition to causing changes in gene frequencies as in standard population genetics models

Animals↗
PubMed1993

Multistep evolution of B-cell-derived tumors in humans and rodents.

At least three genetic changes are known to contribute to the genesis of Burkitt's lymphoma (BL): the Ig/myc translocation, the presence of Epstein-Barr virus (EBV) in the vast majority of the endemic and a minority of sporadic tumors, and a p53 mutation, present in approximately 60% of the BL-derived lines. Activation of c-myc by juxtaposition to Ig sequences is a universal common denominator in endemic and sporadic EBV positive and negative BLs. It acts by preventing the cell from leaving the cycling compartment and by facilitating immune escape. EBV probably acts by expanding the target cell population at risk and prolonging its life span. This, together with the malaria co-factor, would increase the risk of the translocation accident. The p53 mutation may be essential for the continued growth of the tumors where it occurs, since introduction of wild-type p53 leads to their apoptotic death.

Animals↗
PubMed1997

The telencephalon of tetrapods in evolution.

Numerous scientists have sought a homologue of mammalian isocortex in sauropsids (reptiles and birds) and a homologue of sauropsid dorsal ventricular ridge in mammals. Although some of the proposed theories were enormously influential, alternative theories continued to coexist, primarily because the striking differences in pallial organization between adult mammals, sauropsids, and amphibians enabled different authors to enlist different subsets of similarity data in support of different hypotheses of putative homology. A phylogenetic analysis based on parsimony cannot discriminate between such alternative hypotheses of putative homology, because sauropsids and mammals are sister groups. One solution to this dilemma is to include embryological patterns of telencephalic organization in the comparative analysis. Because early developmental stages in different taxa tend to resemble each other more than the adults do, the embryological data may reveal intermediate patterns of organization that provide unambiguous support for a single hypothesis of putative homology. The validity of this putative homology may then be supported by means of a phylogenetic analysis based on parsimony. A comparative analysis of pallial organization that includes embryological data suggests the following set of homologies. The lateral cortex in reptiles is homologous to the piriform cortex in birds and mammals. The anterior dorsal ventricular ridge in reptiles is probably homologous to the neostriatum and ventral hyperstriatum in birds and to the endopiriform nucleus in mammals. The posterior dorsal ventricular ridge in reptiles is most likely homologous to the archistriatum in birds and to the pallial amygdala in mammals. The pallial thickening in reptiles is probably homologous to the dorsal and intercalated portions of the hyperstriatum in birds and to the claustrum proper in mammals. Finally, the dorsal cortex in reptiles is probably homologous to the accessory hyperstriatum and parahippocampal area in birds and to the isocortex in mammals. These hypotheses of homology imply relatively minor evolutionary changes in development but major changes in neuronal connections. Most significantly, they imply the independent elaboration of thalamic sensory projections to derivatives of the lateral and dorsal pallia in sauropsids and mammals, respectively. They also imply the independent evolution of lamination in the pallium of birds and mammals.

Animals↗
PubMed1986

Histologic-prognostic correlations in adenoid cystic carcinoma of major and minor salivary glands of the oral cavity.

Thirty-four cases of adenoid cystic carcinoma (ACC) of the major and minor salivary glands of the oral cavity, treated by wide surgical excision, were studied. The relationship between prognosis of the neoplasm and various morphologic factors were evaluated. Among the morphologic parameters previously studied, which according to various authors may be linked to the evolution of this tumor, we confirmed correlations for both histologic patterns and perineural invasion. In addition, the authors propose neoplastic growth type as a new parameter prognostically significant in ACC. In fact, none of the patients with the pushing type growth pattern died during the study period (p = 0.007). These same patients presented disease-free periods (mean 56 months, median 58 months) significantly longer than those with the infiltrating type growth pattern (mean 28 months, median 24 months).

Carcinoma, Adenoid Cystic↗
PubMed1980

Complete amino acid sequences of the major early embryonic alpha-like globins of the chicken.

Vertebrate embryos contain hemoglobins composed of globin polypeptides structurally distinct from those of adults. Together with fetal and adult globin chains, these early embryonic globins are encoded by two developmentally regulated multigene families. To facilitate analysis of the structure and evolution of early embryonic alpha-globin genes, we have determined the complete amino acid sequences of the pi and pi' alpha-like globins of the chick embryo. While differing from each other by an alanine/glutamic acid interchange at position 124, this pair of sequences differs from the major and minor adult alpha-globins by 43%. The early embryonic and adult alpha-like sequences appear to have diverged following an ancient gene duplication. We discuss specific amino acid substitutions in functional positions as possible mediators of the reduced Bohr effect and elevated oxygen affinity, which are characteristic of early embryonic hemoglobins.

Amino Acid Sequence↗
PubMed1987

Uricoteley:its nature and origin during the evolution of tetrapod vertebrates.

The hepatic mechanism for detoxication of ammonia formed during amino acid gluconeogenesis in uricotelic vertebrates requires the intramitochondrial synthesis of glutamine by glutamine synthetase. This glutamine then serves as a precursor of uric acid in the cytosol. The evolutionary development of uricoteley thus required the localization of glutamine synthetase in liver mitochondria. The mechanism for the mitochondrial import of glutamine synthetase in uricotelic vertebrate liver is not yet known. Tortoises, extant relatives of the stem reptiles, possess both the ureotelic and uricotelic hepatic systems. It therefore seems likely that the genetic events allowing the mitochondrial localization of glutamine synthetase in liver occurred in the amniote amphibian ancestors of the stem reptiles. The selection of ureoteley by the theropsids and of uricoteley by the sauropsids were major events in the divergence and subsequent evolution of these two lines. Once established in the sauropsid line, uricoteley has persisted through to the higher reptiles, crocodilians, and birds. Uricoteley was in part responsible for the radiation of the archosaurs during the Triassic as a water-conserving mechanism in the adult, thereby allowing them to invade the arid environments of that period. Contrary to dogma, uricoteley was probably of minor significance in the development of the cleidoic egg. Neither mammalian nor avian embryonic liver tissues catabolize amino acids to any great extent, so it is inappropriate to attribute to them a kind of "waste" nitrogen metabolism.

Ammonia↗
PubMed2005

WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.

The WNK1 and WNK4 genes have been found to be mutated in some patients with hyperkalemia and hypertension caused by pseudohypoaldosteronism type II. The clue to the pathophysiology of pseudohypoaldosteronism type II was its striking therapeutic response to thiazide diuretics, which are known to block the sodium chloride cotransporter (NCC). Although this suggests a role for WNK1 in hypertension, the precise molecular mechanisms are largely unknown. Here we have shown that WNK1 phosphorylates and regulates the STE20-related kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). WNK1 was observed to phosphorylate the evolutionary conserved serine residue located outside the kinase domains of SPAK and OSR1, and mutation of the OSR1 serine residue caused enhanced OSR1 kinase activity. In addition, hypotonic stress was shown to activate SPAK and OSR1 and induce phosphorylation of the conserved OSR1 serine residue, suggesting that WNK1 may be an activator of the SPAK and OSR1 kinases. Moreover, SPAK and OSR1 were found to directly phosphorylate the N-terminal regulatory regions of cation-chloride-coupled cotransporters including NKCC1, NKCC2, and NCC. Phosphorylation of NCC was induced by hypotonic stress in cells. These results suggested that WNK1 and SPAK/OSR1 mediate the hypotonic stress signaling pathway to the transporters and may provide insights into the mechanisms by which WNK1 regulates ion balance.

Amino Acid Motifs↗
PubMed1988

Rapidly progressive osteoarthrosis of ochronotic origin. A pathologic study.

A case of hip osteoarthrosis associated with ochronosis in a 65-year-old woman is reported. Characteristic features of both conditions were observed macroscopically and on light and electron microscopic examination. In the cartilage the pigment deposits were located on and between thick collagen fibrils. In the synovial membrane there were embedded packets of cartilage shards of which the collagen fibrils and pigment were phagocytosed, as well as calcified bone debris whose disaggregation might have explained the presence of some apatite deposits free of any underlying collagen structure. As also previously observed, the present case of ochronotic hip osteoarthrosis is remarkable for the minor osteophyte formation and for the inclusion of pigmented cartilage shards in the osteomedullar remodeled territory. It also demonstrates a collapse of the femoral head cortex presumably related to the rapid clinical and radiologic evolution. By the well-known origin of its chondropathy and by the pigment labeling of the cartilage, ochronotic arthropathy provides an almost experimental model for analyzing a broader problem, i.e., that of the various components of an osteoarthrotic remodeling.

Aged↗
PubMed1991

Comparison of the bindin proteins of Strongylocentrotus franciscanus, S. purpuratus, and Lytechinus variegatus: sequences involved in the species specificity of fertilization.

Bindin is the sea urchin sperm acrosomal protein that is responsible for the species-specific adhesion of the sperm to the egg. Two new bindin cDNA sequences that contain the entire open reading frame for the binding precursor are reported: one for Strongylocentrotus franciscanus and one for Lytechinus variegatus. Both contain inverted repetitive sequences in their 3' untranslated regions, and the S. franciscanus cDNA contains an inverted repetitive sequence match between the 5' untranslated region and the coding region. The middle third of the mature bindin sequence is highly conserved in all three species, and the flanking sequences share short repeated sequences that vary in number between the species. Cross-fertilization data are reported for the species S. purpuratus, S. franciscanus, L. variegatus, and L. pictus. A barrier to cross-fertilization exists between the sympatric Strongylocentrotus species, but there is no barrier between the allopatric Lytechinus species.

Amino Acid Sequence↗
PubMed1975

[Mixed tumors and cylindromas].

The lacrimals glands may be the focus of the pleomorphic tumours with the same property as the major and minor salivary glands. Their localisation causes different clinical and therapeutic consequences. The cylindromes or Adenoid Cystic Carcinoma are to be put on a parallel with the pleomorphic tumours, though the issue of the clinical evolution is very different for each of them.

Adenoma, Pleomorphic↗