Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “directed evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2005

[Influenza activity 2000/2001].

Influenza viral infections are an important cause of morbidity in all age groups and are associated with a high mortality rate amongst the elderly and in risk groups. The current study analyses data from the epidemiological surveillance of influenza during the 2000/2001-winter season. Clinical, epidemiological and virological data relative to cases of influenza syndrome were collected via the National Influenza Surveillance Scheme, in collaboration with the General Directory of Health and integrates the information obtained by the Network of Sentinel Medical Practitioners and Emergency Units. The data analysis hereby obtained shows a low influenza activity during the 2000/2001-winter season, with an epidemiological period characterized by small duration and intensity. The incidence rate of influenza-like illnesses increased above the base line during three weeks and didn't surpass 74 cases per 1,000,000 inhabitants. Influenza B viruses were predominant with the simultaneous presence of influenza A (H1 and H3). The antigenic and genetic characterisation of the isolates allowed the confirmation of the similarity between these viral strains and the vaccine strains as well as the extent of the antigenic drift. Despite the antigenic similarity between the majority of influenza B isolates and the vaccine strains it's noticeable that the genetic characteristics showed an evolution directed towards the B/Sichuan/379/99 strain, which would later be incorporated in the 2001/2002 influenza vaccine. The co-circulation of two different lineages was consequently observed by the phylogenetic analysis of the B strains isolated in our country.

Adolescent↗
PubMedDate not supplied

[Aneurysm of the splenic artery].

The work is presenting the case of a young patient with splenic aneurysm, a more and more frequent diagnosis in these last years. The peculiarity consist in the biphase and bi-directional evolution, first toward the gastric lumen, with hematemesis and consequently, after about a month, in the peritoneal cavity, with hemoperitoneum. The positive diagnosis and the final surgical solution was obtained after successive procedures, due to the lack of an appropriate technical equipment (angiographic exploration) due to the lack of the medical information at one time (inefficient anamnesis and the lack of the documentation) and finally, due to some elements that disturbed the surgical reasoning.

Adult↗
PubMedDate not supplied

[Metabolic monitoring of heart surgery patients during the immediate postoperative period].

The situation of aggression is accompanied by metabolic alterations with an important neuro-endocrinal context. Extracorporeal surgery is an especially aggressive situation which involves both surgery and the added metabolic state of hypothermia. In 48 patients subjected to extracorporeal circulation with hypothermia, the metabolic parameters of Oxygen Consumption (VO2), Production of carbon dioxide (VCO2), Respiratory Quotient (RQ) and Energy Expenditure (GE) were studied. It was observed that the patients could be divided into two subgroups, depending on their metabolic response. Studying the RQ parameter, it was seen that this divided patients into two subgroups depending on their posterior evolution. Patients in whom RQ did not exceed 0.8 showed more favourable evolution than those in whom RQ was higher than 0.8. The correct metabolic response was regarded as a parameter indicative of the evolution, directly correlated to the hemodynamic parameters studied. In one patient, creatine phosphate was infused at a dosage of 30 mg/kg for 60 min, and an improvement was noted in GE and Cardiac Index. It was concluded that the intravenous intake of creatine phosphate in patients undergoing extracorporeal surgery improved both metabolic parameters and the myocardiac function.

Adult↗
PubMedDate not supplied

[The thermodynamic direction of biological evolution. The model and the reality].

A macrothermodynamic model of evolution of the supramolecular structures and chemical composition of living objects during ontogenesis and at long-term stages of general biological evolution is presented. A study of quasiclosed (thermodynamically and kinetically) systems, phases of the biomass supramolecular structures, enables a conclusion on the thermodynamic direction of biological evolution to be made. In correspondence with the second principle, this direction leads to variations in the chemical composition and structure of the living systems during their development. Indirect and direct evidence of the trend to a minimal Gibbs specific function of formation of the supramolecular structures in animal tissues during ontogenesis are presented. The conclusion that thermodynamics is the "driving force" of evolution of the biological world is confirmed.

Animals↗
PubMed2001

Frogs without polliwogs: evolution of anuran direct development.

Direct development is the assumption of the adult morphology without progression through an intervening, morphologically distinct, free-living larval phase. We discuss the ecological factors contributing to the evolution of this derived life-history strategy in frogs, and the developmental modifications that facilitate such an unusual mode of embryogenesis. Studies on the Puerto Rican tree frog, Eleutherodactylus coqui, have identified several such modifications, including developmental adaptations for dealing with increased egg size, and loss of tadpole structures. Surprisingly, this direct developer still undergoes a thyroid hormone-dependent metamorphosis, which occurs before hatching. We suggest how the ancestral biphasic developmental pattern may have been rearranged during the evolution of direct development.

Animals↗
PubMed2002

Cell-selfish modes of evolution and mutations directed after transcriptional bypass.

During transcription, prokaryotic and eukaryotic RNA polymerases bypass and misread (transcriptional mutagenesis) several classes of DNA lesions. For example, misreading of 8-OH-dG generates mRNAs containing G to T transversions. After translation, if the mutant protein briefly allowed the cell a growth-DNA replication advantage, then precocious DNA replication would bypass that unrepaired 8-OH-dG and misinsert dA opposite the directing DNA lesion with a higher probability than would be experienced for 8-OH-G lesions at other positions in otherwise identical neighboring cells. Such retromutations would have been tested for their imparted growth advantage as mRNA before they became heritable DNA mutations. The logical properties of a mode of evolution that utilizes directed-retromutagenesis were compared one by one with those of the standard neo-Darwinian mode. The retromutagenesis mode, while minimizing mutational load, is cell-selfish; fitness is for an immediate growth advantage rather than future reproductive potential. In prokaryotes, an evolutionary mode that involves standard Darwinian fitness testing of novel alleles in the genetic background of origin followed by clonal expansion also favors cell-selfish allele combinations when linkage disequilibrium is practiced. For metazoa and plants to have evolved organized tissues, cell-selfish modes of evolution represent systems-poisons that must be totally suppressed. The feedback loops that allow evolution to be cell-serving in prokaryotes are actively blocked in eukaryotes by traits that restrict fitness to future reproductive potential. These traits include (i) delay of fitness testing until after the mutation is made permanently heritable, (ii) diploidy to further delay fitness testing, (iii) segregation of somatic lines from germ lines, (iv) testing of novel alleles against randomized allele combinations constructed by obligate sex, and (v) obligate genetic death to insure that that the most basic systems unit of selfish allele combinatorial uniqueness is the species instead of the cell. The analyses indicate that modes of evolution in addition to our neo-Darwinian one could have existed utilizing known molecular mechanisms. The evolution of multicellularity was as much the discarding of old cell-selfish habits as the acquisition of new altruistic ones.

Alleles↗
PubMed2004

A novel ADP- and zinc-binding fold from function-directed in vitro evolution.

A great challenge to biologists is to create proteins with novel folds and tailored functions. As an alternative to de novo protein design, we investigated the structure of a randomly generated protein targeted to bind ATP. The crystal structure reveals a novel alpha/beta fold bound to its ligand, representing both the first protein structure derived from in vitro evolution and the first nucleotide-binding protein stabilized by a zinc ion.

Adenosine Diphosphate↗
PubMed2003

Directed parathyroid exploration: evolution and evaluation of this approach in a single-institution review of 346 patients.

OBJECTIVES/HYPOTHESIS: Critical evaluation of a directed exploration protocol used by a single surgeon in the management of surgical parathyroid disease. STUDY DESIGN: Retrospective chart review was made of patients surgically managed for hyperparathyroidism at an academic tertiary care center. METHODS: Three hundred forty-six patients were evaluated for biochemically proven hyperparathyroidism between March 1995 and February 2002. A directed exploration protocol was implemented in appropriately selected patients with primary hyperparathyroidism and in patients with secondary or tertiary hyperparathyroidism requiring repeat operation. The protocol included preoperative technetium-99m sestamibi imaging for hyperfunctional parathyroid localization, targeted neck exploration, rapid intraoperative parathyroid hormone determination, and limited-stay discharge from the ambulatory surgical recovery unit. Data collection was accomplished by entering patient evaluation, management, and outcome information prospectively into collective case report forms. A retrospective analysis of the data was conducted for the purpose of evaluating the effectiveness of the protocol. RESULTS: Sustained normocalcemia beyond 6 months postoperatively was achieved in 323 of 327 (99%) patients with primary hyperparathyroidism. Eighty-four percent (84%) of patients with secondary or tertiary hyperparathyroidism achieved normocalcemia or had resolution of symptoms as a measure of therapeutic success. The complication rate for the entire series of patients was 2.8%. Ninety-two percent of positive findings on sestamibi scan correctly predicted the location of an adenoma, whereas a negative finding accurately predicted the absence of an enlarged gland in a "usual" location in 81% of patients. Twenty-six patients (9%) had a false-positive finding on the scan, whereby a solitary adenoma was found contralateral to the side indicated by the scan. Overall, the positive predictive value for sestamibi imaging in the series was 91%. Intraoperative parathyroid hormone determination yielded an overall rate of reduction of 80% from preoperative levels during directed exploration. Sustained normocalcemia was achieved in all patients in whom intraoperative parathyroid hormone determination demonstrated a minimum decline of 50% from preoperative levels following resection of hyperfunctional parathyroid tissue (adenoma[s]). The majority (72%) of patients were managed in an outpatient (ambulatory surgery) setting and were discharged to home within 8 to 12 hours after surgery. CONCLUSION: The directed exploration protocol for surgical management of hyperparathyroidism generated surgical rates of success that were as good as and, in most cases, improved over that of traditional bilateral exploration. This achievement was associated with low morbidity and reduced time and facility utilization, conveying improved cost-effectiveness. This surgical strategy should serve to enhance the capability of the surgeon to safely and efficiently manage the majority of patients with surgical parathyroid disease.

Adolescent↗
PubMed1999

Directional substitution and evolution of nucleotide content in the cytochrome oxidase II gene in earwigs (dermapteran insects).

The cytochrome oxidase subunit II (COII) gene was sequenced for six dermapteran species. The nucleotide composition of this gene is biased in most animals. While the CG content of other insect orders is low (mean, 27.6%; range, 19.5%-33.1%), species from the Forficula genus showed unusually high values (mean, 42.4%; range, 37.3%-44.1%), mostly due to high CG frequencies at third codon positions: the mean CG content at these positions was around 45% (range, 43.9%-46.9%) for Forficula, compared with only 13.3% for other insects. This effect was so strong that in one species, Forficula lesnei, there was no significant difference between the frequencies of the four bases. During evolution, this loss of bias has involved a significant increase in the synonymous substitution rate and an increase of transitions over transversions compared with other insects. A strong directionality of substitutions has favored T-->C and A-->G changes. This phenomenon was also observed between two conspecific populations of Forficula auricularia. A species from a closely related genus, Anechura bipunctata, was intermediate between Forficula and other insects for these parameters, while two remotely related dermapteran species, Labidura riparia and Euborellia moesta, were similar to other insects. These results suggest that the evolution of Forficula DNA content has been both rapid and recent.

Animals↗
PubMed2004

Hominin brain evolution--new century, new directions.

The study of hominin brain evolution focuses on the interiors of fossilized braincases. Applications of recent three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) techniques for visualizing and measuring >>virtual endocasts<< from braincases in combination with advances in computer graphics and software for acquiring relevant data are transforming the way in which fossil skulls are analyzed, and improving the quality of paleoneurological investigations. Although CT imaging is preferred for fossil skulls, a novel method that combines high-resolution MRI of physical endocasts, electronic reconstruction of their missing parts, and warping of the resulting virtual endocasts is currently being developed and has great potential for future studies of hominin brain evolution. Applications of CT and MR techniques have already resulted in surprising new findings, which are briefly outlined. Exciting revelations about hominin brain evolution are expected as the 21st century unfolds.

Animals↗
PubMedDate not supplied

Developmental drive: an important determinant of the direction of phenotypic evolution.

Over any period of evolutionary time, the prevailing ontogenetic trajectory within a lineage may either recur unchanged from generation to generation (stasis) or alter (developmental reprogramming). A key question about reprogramming is whether it exhibits intrinsic biases in favor of some sorts of change and against others, which may be referred to respectively as "drive" and "constraint." A simple logical argument suggests that both drive and constraint should be common, and conversely that cases of equiprobable modification in various phenotypic directions should be relatively rare. These proposals, that drive and constraint exist and that they are common, appear to be widely accepted, even among neo-Darwinians, who are sometimes portrayed as rejecting them. What is more controversial is that developmental drive (and constraint) can have a powerful influence on the direction of evolutionary change. It is argued that such an influence will occur, and indeed may be pervasive.

Developmental Biology↗
PubMed1995

Microsatellite evolution--evidence for directionality and variation in rate between species.

Microsatellite DNA sequences are rapidly becoming the dominant source of nuclear genetic markers for a wide range of applications, from genome mapping to forensic testing to population studies. If misinterpretation is to be avoided, it is vital that we understand fully the way in which microsatellite sequences evolve. We have therefore compared allele length distributions for 42 microsatellites in humans with their homologues in a range of related primates. We find a highly significant trend for the loci to be longer in humans, showing that microsatellites can evolve directionally and at different rates in closely related species.

Alleles↗
PubMed2005

Current directions in the evolution of compound libraries.

Synthetic compound libraries have been available for over a century, but in the last 15 years they have become increasing important in early-stage drug discovery projects. The qualities that these libraries possess impart a dramatic effect on hit discovery, on the subsequent steps of hit-to-lead progression, and on lead optimization by medicinal chemists. More recently, synthetic libraries have found an important application in chemical genetics. Concurrently, ideas have evolved regarding the application of the different types of synthetic approaches that are variously described as combinatorial chemistry, high-throughput synthesis, or diversity-oriented synthesis. This review will discuss current directions of synthetic chemistry, natural product chemistry and chemoinformatics, which relate to the various types of compound libraries that are in use in drug discovery and chemical genetics.

Animals↗
PubMed1999

Emergence of a dual-catalytic RNA with metal-specific cleavage and ligase activities: the spandrels of RNA evolution.

In vitro selection, or directed molecular evolution, allows the isolation and amplification of rare sequences that satisfy a functional-selection criterion. This technique can be used to isolate novel ribozymes (RNA enzymes) from large pools of random sequences. We used in vitro evolution to select a ribozyme that catalyzes a novel template-directed RNA ligation that requires surprisingly few nucleotides for catalytic activity. With the exception of two nucleotides, most of the ribozyme contributes to a template, suggesting that it is a general prebiotic ligase. More surprisingly, the catalytic core built from randomized sequences actually contains a 7-nt manganese-dependent self-cleavage motif originally discovered in the Tetrahymena group I intron. Further experiments revealed that we have selected a dual-catalytic RNA from random sequences: the RNA promotes both cleavage at one site and ligation at another site, suggesting two conformations surrounding at least one divalent metal ion-binding site. Together, these results imply that similar catalytic RNA motifs can arise under fairly simple conditions and that multiple catalytic structures, including bifunctional ligases, can evolve from very small preexisting parts. By breaking apart and joining different RNA strands, such ribozymes could have led to the production of longer and more complex RNA polymers in prebiotic evolution.

Animals↗
PubMed1996

Tandem arrangement of the human serum albumin multigene family in the sub-centromeric region of 4q: evolution and chromosomal direction of transcription.

The albumin gene family is comprised of four genes encoding: serum albumin (ALB), alpha-fetoprotein (AFP), alpha-albumin (ALF), and vitamin D-binding protein (DBP; also known as GC). The genes are regulated developmentally, expressed in the liver, and the proteins are secreted into the bloodstream. The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13. Using techniques of fluorescence in situ hybridization to chromatin fibres, chromosome walking and DNA sequencing of genomic clones, we now report on the chromosomal location of the ALF gene and the organization of the entire gene family. The four genes are tandemly linked in the 4q sub-centromeric region: 5'ALB-5'AFP-5'ALF-5'GC3'-centromere, and hence are transcribed in the same, centromere-bound, direction. The linear arrangement of the four genes along the chromosome is not correlated with their temporal expression in the human ontogeny. It appears that GC is very close (and may be the gene proximal) to the centromere. The linear chromosomal arrangement of the four genes and the structural differences between them are congruent with the following evolutionary divergence of the gene family. Starting with the first duplication of an ancestral progenitor gene, a single evolutionary line led to the contemporary GC, leaving ALB/AFP/ALF on the other line of descent. The second duplication occurred in this ALB lineage, giving rise to ALB and the AFP/ALF progenitor, and the third, most recent one, gave rise to the AFP-ALF pair.

Albumins↗
PubMed2005

Cenozoic biogeography and evolution in direct-developing frogs of Central America (Leptodactylidae: Eleutherodactylus) as inferred from a phylogenetic analysis of nuclear and mitochondrial genes.

We report the first phylogenetic analysis of DNA sequence data for the Central American component of the genus Eleutherodactylus (Anura: Leptodactylidae: Eleutherodactylinae), one of the most ubiquitous, diverse, and abundant components of the Neotropical amphibian fauna. We obtained DNA sequence data from 55 specimens representing 45 species. Sampling was focused on Central America, but also included Bolivia, Brazil, Jamaica, and the USA. We sequenced 1460 contiguous base pairs (bp) of the mitochondrial genome containing ND2 and five neighboring tRNA genes, plus 1300 bp of the c-myc nuclear gene. The resulting phylogenetic inferences were broadly concordant between data sets and among analytical methods. The subgenus Craugastor is monophyletic and its initial radiation was potentially rapid and adaptive. Within Craugastor, the earliest splits separate three northern Central American species groups, milesi, augusti, and alfredi, from a clade comprising the rest of Craugastor. Within the latter clade, the rhodopis group as formerly recognized comprises three deeply divergent clades that do not form a monophyletic group; we therefore restrict the content of the rhodopis group to one of two northern clades, and use new names for the other northern (mexicanus group) and one southern clade (bransfordii group). The new rhodopis and bransfordii groups together form the sister taxon to a clade comprising the biporcatus, fitzingeri, mexicanus, and rugulosus groups. We used a Bayesian MCMC approach together with geological and biogeographic assumptions to estimate divergence times from the combined DNA sequence data. Our results corroborated three independent dispersal events for the origins of Central American Eleutherodactylus: (1) an ancestor of Craugastor entered northern Central America from South American in the early Paleocene, (2) an ancestor of the subgenus Syrrhophus entered northern Central America from the Caribbean at the end of the Eocene, and (3) a wave of independent dispersal events from South America coincided with formation of the Isthmus of Panama during the Pliocene. We elevate the subgenus Craugastor to the genus rank.

Animals↗
PubMed2001

Use of spoligotyping to study the evolution of the direct repeat locus by IS6110 transposition in Mycobacterium tuberculosis.

Based on the variability of 43 spacers within the direct repeat (DR) locus of Mycobacterium tuberculosis complex organisms, spoligotyping is a rapid method that aids in the study of the epidemiology of tuberculosis. It was recently hypothesized that despite its presence in the DR locus, spacer 31 could not be amplified in M. tuberculosis clinical isolates belonging to spoligotype 50 due to the insertion of an extra copy of IS6110 between spacers 31 and 32 that could lead to an asymmetrical split of the primer targets (I. Filliol, C. Sola, and N. Rastogi, J. Clin. Microbiol. 38:1231--1234, 2000). In the present investigation, previous observations were extended to 25 clinical isolates of type 50 showing that the primer set IS6-DRb that selectively amplified the left and central DR regions was indeed able to demonstrate the presence of spacer 31. IS6110-restriction fragment length polymorphism (RFLP) and DR-RFLP showed that type 50 isolates were characterized by the presence of two copies of IS6110 associated with the DR locus and an additional double IS6110 band of 1.4 kb. The primer set IS3-IS6 was then used to selectively amplify a 750-bp inter-IS6110 fragment within the DR locus. The sequencing of the central DR region corroborated our previous findings and showed that the absence of spacer 31 among the type 50 isolates was due to the asymmetric insertion of an extra copy of IS6110 between spacers 31 and 32, leading to an unequal split of the DRa-DRb target into two portions, of 6 and 30 bp, respectively. These results show that the DR locus constitutes an ideal IS6110 preferential locus (ipl), permitting the insertion of two or more copies of IS6110, and provide new clues for epidemiological and phylogenetic interpretation of changes in IS6110-RFLP and spoligotyping profiles.

Bacterial Typing Techniques↗