No directionality of short tandem repeat evolution at the HPRT locus in catarrhine primates.
Explore the source record for details and available documents.
Animals↗
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.
Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.
Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.
Dependovirus↗
[Acquisition of masticatory structures in mammalian reptiles (preliminary study].
Possession of the masticatory function and apparatus appears as essential for the passage from Reptiles to Mammals. The present study, based on material of the Museum of d'Histoire Naturelle of Paris and on the literature, tries to distinguish the different stages of modification and specialization of feeding device in the cynodont theriodonts, leading to the mammalian stomatognathic system. The relationship between bone components (lateral skull and lower jaw), teeth and muscles are discussed. Induction of these changes comes from the external adductor muscular system in which the transformation from a primitive mass to mammalianlike masticatory muscles, directs this evolution. The conditions of feeding specialization of the Gomphodonts are discussed, as well as their evolutionary failure. Lastly, without taking up the quarrel about the double jaw-joint, it seems for the authors that the jaw-joint transformation appears as the most determinative element for assigning mammalian origins to the Cynodonts.
Animals↗
Converting catabolic ornithine carbamoyltransferase to an anabolic enzyme.
Pseudomonas aeruginosa has an anabolic and a catabolic ornithine carbamoyltransferase (OTCase). In vitro, these homologous enzymes catalyze the same reaction (ornithine + carbamoyl phosphate (CP) in equilibrium citrulline + Pi), yet in vivo they function unidirectionally owing to specific kinetic properties. The catabolic OTC-ase cannot promote the anabolic reaction (citrulline formation) in vivo because of a sigmoidal CP saturation curve and a high CP concentration for half-maximal velocity. The structural basis for this kinetic specialization was examined. The catabolic OTCase lost most of its homotropic cooperativity and gained anabolic activity when an amino acid residue near the CP binding site, Glu-106, was replaced by alanine or glycine. In the anabolic OTCase of Escherichia coli the glutamine residue corresponding to Glu-106 was exchanged for glutamate; however, in this case no CP cooperativity was acquired. Thus, in catabolic OTCase, sequence features in addition to Glu-106 are important for sigmoidal CP saturation, and such a sequence was identified in the C-terminal part. By an in vivo gene fusion technique the 9 C-terminal amino acids of catabolic OTCase were replaced by the homologous 8 amino acids from anabolic OTCase of E. coli; the hybrid enzyme had a markedly reduced homotropic cooperativity. This gene fusion method should be generally useful for directed enzyme evolution.
Amino Acid Sequence↗
[The direction and motivation for an evolution in methods of antiulcer surgery].
A 23-year retroactive analysis of a heterogeneous series of observations with unfavourable tardy results after antiulcer surgeries showed that the most failures requiring a second surgery appear after large resections with gastrojejunal or gastroduodenal anastomosis and after vagotomies associated with gastric drainage. The most favourable tardy results followed the vagotomy associated with limited gastric resection (hemigastrectomy). This kind of intervention prevents the appearance of the ulcerous relapses and lowers significantly the incidence of the other type of post-surgical iatrogenic complications. The optimal protection against the ulcerous relapse given by vagotomy associated with hemigastrectomy permits a tactical adaptation of the intervention to the lesional and physiopathological characteristics of each case.
Anastomosis, Surgical↗
[Comparative study of the temporal evolution through approximation obtained by direct or indirect observation of the extended and contracted postural conditions of human subjects residing at two conditions of air temperature].
Explore the source record for details and available documents.
Adult↗
Effects of 2,4-dinitrophenol and other metabolic inhibitors on the thermograms of Ehrlich ascites carcinoma cells registered with a microcalorimeter.
The heat produced by Ehrlich ascites carcinoma cells was measured microcalorimetrically to investigate the characteristics of the energetics of these cells. 2,4-Dinitrophenol and other inhibitors were used to obtain the standard thermograms. The heat level of starved Ehrlich ascites carcinoma cells (endogenous) was almost constant and linear and depended on the cell number used in the experiments (about 1 cal/1 X 10(8) cells/hr). The endogenous heat generation was suppressed strongly by potassium cyanide but not by iodoacetic acid or 2,4-dinitrophenol. On the other hand, heat evolution was directly related to the amount of glucose added to the medium but not to the number of cells (19 cal/mmol of glucose). The addition of iodoacetic acid markedly suppressed heat generation, but potassium cyanide did not. In contrast, glucose with dinitrophenol increased heat production markedly to about 10% higher than that of the control, possibly due to the uncoupled energy from oxidative phosphorylation. Malonic acid (1 mM) suppressed slightly the endogenous heat but caused a 15% reduction in exogenous heat. The amount of heat produced by the addition of glucose (19 cal/mmol) was equivalent to 40% of the theoretical value of energy released through glycolysis (47 cal/mmol). Thus, the heat produced by exogenous glucose appears to be mainly dependent on glycolysis.
2,4-Dinitrophenol↗
Ureteric hemorrhage in hemophilia with rapid healing.
A rapidly regressing ureteric hemorrhage, probably intramural, in a 14-year-old hemophiliac, is demonstrated by two closely sequential intravenous urograms. In the presence of hematuria, the intravenous urogrom outlines both the complications of hemophilia and their evolution, often directing therapy, and identifies concurrent disease.
Adolescent↗
Repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile.
We previously demonstrated that repeated application of 2,4,6-trinitro-1-chlorobenzene resulted in a site-restricted shift in the time course of Ag-specific hypersensitivity responses from a typical delayed-type to an early-type response. Here we demonstrated that the cutaneous microenvironment at the time of Ag presentation to T cells in the elicitation, but not the induction, phase of contact hypersensitivity is responsible for the shift. To investigate the differences in the cutaneous cytokine milieu between the acute and chronic phases of contact hypersensitivity, sequential cytokine dynamics after 2,4,6-trinitro-1-chlorobenzene application were assessed in the acute vs chronic lesions. In the acute lesions, increased mRNA levels for IFN-gamma and IL-2 were rapidly detected at 1 h and remained elevated at 12 h, while mRNA expression for IL-4 and IL-10 was minimally up-regulated between approximately 12 and 24 h. In chronic lesions, high levels of constitutive expression of IL-4 mRNA were observed and IL-10 mRNA was dramatically up-regulated at 1 approximately 3 h in an Ag-specific fashion, whereas the expression of Th1-type cytokines was markedly reduced. Increased mRNA levels for Th2-type cytokines in the chronic lesions was also reflected at the protein level. These results indicate that repeated elicitation with Ag alters the balance of cytokines released locally, with a shift toward Th2-dominated responses, which would represent the natural evolution processes directed toward reducing a more deleterious Th1 response.
Administration, Cutaneous↗
Benign prostatic hyperplasia.
Insight into the dysfunctional physiology of benign prostatic hyperplasia has expanded appropriate therapies. As the proportion of the population to whom BPH will be a problem increases our attention is directed to evolution in clinical management.
Adrenergic alpha-Antagonists↗
Senior executive behaviors for the Army Dental Care System of the 21st century.
Challenges will most likely confront the Army Dental Care System as it moves into the next century. Like any other learning organization, the Army dental care system must develop a continuous stream of dynamic leaders to direct its evolution if it wants to survive. Using the Delphi method, the investigators surveyed senior dental leaders to determine the attitudes and behaviors believed to be required to perform successfully as commanders, residency directors, and senior staff officers. The essential executive behaviors appear to be consistent: be honest, act with integrity, be accountable for your actions, be dedicated to mission accomplishment, and perform your duty with care and compassion. Relying solely on ratings assigned to the behaviors, discriminant function analyses could predict proper group membership with an accuracy of 79.4%. When demographic information was included, prediction accuracy improved to 96.7%.
Adult↗
Short- and long-term projections about the use of drug metabolism in drug discovery and development.
The science of drug metabolism, like any other science, has advanced from simple beginnings (by today's standards) to its present state. One can examine the path that has been taken to understand the forces driving the direction of evolution of this science. The trends discovered can then be used to make reasonable extrapolations about the changes that might be expected in the future. That exercise is the subject of this article. The main focus will be on drug metabolism as practiced in the industrial environment, representing the author's main experience as well as the principal arena of practical applications of the science. The discussion will draw mainly on broad phenomena occurring in this application of drug metabolism to drug discovery and development.
Animals↗
Directional mutation pressure, mutator mutations, and dynamics of molecular evolution.
Using a general form of the directional mutation theory, this paper analyzes the effect of mutations in mutator genes on the G+C content of DNA, the frequency of substitution mutations, and evolutionary changes (cumulative mutations) under various degrees of selective constraints. Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place. This prediction explains the wide variation of the DNA G+C content among unicellular organisms and possibly also the wide intragenomic heterogeneity of third codon positions for the genes of multicellular eukaryotes. The present analyses lead to several predictions that are not consistent with a number of the frequently held assumptions in the field of molecular evolution, including belief in a constant rate of evolution, symmetric branching of phylogenetic trees, the generality of higher mutation frequency for neutral sets of nucleotides, the notion that mutator mutations are generally deleterious because of their high mutation rates, and teleological explanations of DNA base composition.
Animals↗
Directional fixation of mutations in vertebrate evolution.
We have made pairwise comparisons between the coding sequences of 21 genes from cold-blooded vertebrates and 41 homologous sequences from warm-blooded vertebrates. In the case of 12 genes, GC levels were higher, especially in third codon positions, in warm-blooded vertebrates compared to cold-blooded vertebrates. Six genes showed no remarkable difference in GC level and three showed a lower level. In the first case, higher GC levels appear to be due to a directional fixation of mutations, presumably under the influence of body temperature (see Bernardi and Bernardi 1986b). These GC-richer genes of warm-blooded vertebrates were located, in all cases studied, in isochores higher in GC than those comprising the homologous genes of cold-blooded vertebrates. In the third case, increases appear to be due to a limited formation of GC-rich isochores which took place in some cold-blooded vertebrates after the divergence of warm-blooded vertebrates. The directional changes in the GC content of coding sequences and the evolutionary conservation of both increased and unchanged GC levels are in keeping with the existence of compositional constraints on the genome.
Animals↗
Turnover of mouse intestinal brush border membrane proteins and enzymes in organ culture. A direct evaluation from studies on the evolution of enzyme activities during the culture.
The turnover of mouse intestinal brush border membrane enzymes has been studied by kinetic analysis of the evolution of enzyme activities during organ culture. By comparing the results obtained in these studies with the predictions from a mathematical model of enzyme synthesis and degradation in organ cultures, it has been possible to reach the following conclusions: (1) There is no degradation of brush border membrane enzymes during culture and the rate of synthesis of each enzyme is directly measurable from the kinetics of total enzyme accumulation (tissue + media). (2) Brush border membrane enzymes are released in culture media by two complementary processes. The first one involves a differential solubilization of enzymes but its exact nature cannot be exactly stated. The second one involves a microvesiculation of brush border membranes, the importance of which in vivo is seen in the possible conciliation between urinary membrane synthesis and heterogeneous turnover of membrane components.
Alkaline Phosphatase↗
[Evolution of the locomotor-sensory systems].
Among directing physical factors of evolution of the locomotor-sensory system (LSS) gravitation, photons energy, oscillations of water and air media, ligands play the main role. At the molecular level the LSS elements are formed on the base of synthesizing genes that bring about development of protein molecules of tubulin and specific protonizing proteins in composition of the locomotor apparatus in Procariota flagellas. Tubulin and dinein with ATPh-ase activity are included in the flagella composition of LSS in Eukaryota, actin and miozin--with a high ATPh-ase activity--in composition of LSS myofilaments in ameboid Eukaryota and locomotor musculature in Metazoa. Simultaneously, in Pro- and Eukaryota in the same cell sensory molecules of rhodopsin, mechanoreceptors, chemoreceptors and so on can be synthesized. As a rule they localize in the flagellar membranes. In Metazoa single receptory flagellar cells are differentiated; they realize conservatively some receptive molecules that are already prepared by their ancessors--Eukaryota. The molecules also preserve their localization in the flagellar membranes. In Metazoa two types of locomotion take place according to the function of regulatory genes: initial flagellar and muscular definitive apparatus. Both types of locomotion are directed and regulated by the organs of sense and CNS; they form a strict spatial model of fixated synaptic connections of LSS. For the first time it was discovered in Ctenophora. This model, despite a complicated organization, is conservatively preserved in its general form in all Proto- and Denterostomia.
Animals↗
A theory of evolution above the species level.
Gradual evolutionary change by natural selection operates so slowly within established species that it cannot account for the major features of evolution. Evolutionary change tends to be concentrated within speciation events. The direction of transpecific evolution is determined by the process of species selection, which is analogous to natural selection but acts upon species within higher taxa rather than upon individuals within populations. Species selection operates on variation provided by the largely random process of speciation and favors species that speciate at high rates or survive for long periods and therefore tend to leave many daughter species. Rates of speciation can be estimated for living taxa by means of the equation for exponential increase, and are clearly higher for mammals than for bivalve mollusks.
Adaptation, Biological↗
Malignant melanoma metastatic to the upper gastrointestinal tract: endoscopic and radiologic correlations, form and evolution of lesions, and value of directed biopsy in diagnosis.
Explore the source record for details and available documents.
Adult↗