PubMed HealthSearch

SEARCH · PubMed Health

Results for “Generational stabilization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 109 records · Page 6Linked to original sources

[Establishment of transplantable HL-60 xenograft lines in athymic nude mice].

In vivo models of HL-60 cells were successfully established as ascites and/or solid forms in nude mice (BALB/c, nu/nu). HL-60 ascites and solid tumor cells produced 100% lethal takes after their 7th transplant generation and were stabilized at serial transplant intervals of 14 and 40 days respectively. Morphological studies demonstrated that the ascites and solid tumor cells exhibited morphological characteristics similar to those of HL-60 cells in vitro. The establishment of transplantable HL-60 xenograft lines provides a potential tool for the screening of effective differentiation inducers.

Animals

[Photochemical electron transfer in reaction centers of photosynthesis].

Recent works of the Laboratory are reviewed in terms of modern concepts on the nature of primary photoprocesses in reaction centers of photosynthesis. The main feature of the primary charge separation in reaction centers is the fast (within several picoseconds) electron transfer between the pigments of chlorophyllous nature followed by electron transfer stage to nonchlorophyllous electron carriers for several hundreds of picoseconds The primary charge separation is determined by the ability of excited chlorophyll and its analogues to be reversibly oxidized or reduced as well as by peculiar molecular arrangement of pigment system in reaction centers. The stabilization of photochemically generated electron and the hole is realized at the expense of its spatial separation and some loss of energy in the course of electron transfer.

Bacterial Proteins

NADPH-generating system: influence on microsomal mono-oxygenase stability during incubation for the liver-microsomal assay with rat and mouse S9 fractions.

Activity levels of 7-ethoxycoumarin O-deethylase (ED), aminopyrine N-demethylase (APD), p-nitroanisole O-demethylase (p-NAD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were determined in incubation mixtures for the liver-microsomal assay (LMA) at time 0 and after 1 and 2 h incubation under conditions for mutagenic assay. The experiments were performed with S9 liver fractions from mice (induced with Na-phenobarbital and beta-naphthoflavone) and rats (induced with Aroclor 1254) with and without G-6-PDH in the incubation mixtures. In the absence of G-6-PDH the activities were significantly lower at time 0 in the mouse. The pattern of stability, however, was similar for the activities, with an increase of stability after 1 and 2 h of pre-incubation (an exception for p-NAD). Only ED activity showed a similar behaviour in the rat. No differences were present for APD and p-NAD activities at time 0 in the rat, but the enzyme stabilities were significantly decreased after 2 h of incubation (about 15% and 10% for APD and p-NAD respectively) in the absence of G-6-PDH. At time 0, the amounts of G-6-PDH differed between mouse and rat fractions; however, during the incubations for LMA they decreased by about 57% and 53% for the two species, respectively. In addition to the above biochemical results, the presence of exogenous G-6-PDH in the incubations for the mutagenic assay, significantly increased the mitotic gene conversion and mitotic crossing-over of dimethylnitrosamine (DMN) and AR2MNFN (a nitroimidazo[2,1-b]thiazole) in the D7 strain of Saccharomyces cerevisiae.

7-Alkoxycoumarin O-Dealkylase

Cleavage within an RNase III site can control mRNA stability and protein synthesis in vivo.

We report that processing at a cloned bacteriophage T7 RNase III site results in strong stabilization of the mRNA relative to the full-length transcript. In contrast, processing by RNase III of the bacteriophage lambda int transcript leads to rapid degradation of the messenger. It is proposed that the mode of cleavage within the RNase III site determines mRNA stability. Single cleavage leaves part of the phage T7 RNase III site in a folded structure at the generated 3' end and stabilizes the upstream mRNA whereas double cleavage at the lambda int site removes the folded structure and accelerates degradation. In addition, the processed transcript is as active a messenger as the unprocessed one and can direct protein synthesis for longer times. This increased efficiency is accompanied by a proportional (3-4 fold) increase in protein levels. In contrast, processing at the lambda int site reduces Int synthesis. Thus, processing may either stabilize mRNA and stimulate gene expression or destabilize a messenger and prevent protein synthesis. The end result appears to be determined by the mode of cleavage within the RNase III site.

DNA Restriction Enzymes

Codon usage determines translation rate in Escherichia coli.

We wish to determine whether differences in translation rate are correlated with differences in codon usage or with differences in mRNA secondary structure. We therefore inserted a small DNA fragment in the lacZ gene either directly or flanked by a few frame-shifting bases, leaving the reading frame of the lacZ gene unchanged. The fragment was chosen to have "infrequent" codons in one reading frame and "common" codons in the other. The insert in these constructs does not seem to give mRNAs that are able to form extensive secondary structures. The translation time for these modified lacZ mRNAs was measured with a reproducibility better than plus or minus one second. We found that the mRNA with infrequent codons inserted has an approximately three-seconds longer translation time than the one with common codons. In another set of experiments we constructed two almost identical lacZ genes in which the lacZ mRNAs have the potential to generate stem structures with stabilities of about -75 kcal/mol. In this way we could investigate the influence of mRNA structure on translation rate. This type of modified gene was generated in two reading frames with either common or infrequent codons similar to our first experiments. We find that the yield of protein from these mRNAs is reduced, probably due to the action in vivo of an RNase. Nevertheless, the data do not indicate that there is any effect of mRNA secondary structure on translation rate. In contrast, our data persuade us that there is a difference in translation rate between infrequent codons and common codons that is of the order of sixfold.

Bacterial Proteins

Cell wall assembly in Bacillus megaterium: incorporation of new peptidoglycan by a monomer addition process.

The pattern of cross-linking in the peptidoglycan of Bacillus megaterium has been studied by the pulsed addition of radiolabeled diaminopimelic acid. The distribution of label in muropeptides, generated by digestion with Chalaropsis muramidase and separated by high-performance liquid chromatography, stabilized after 0.15 of a generation time. The proportion of label in the acceptor and donor positions of isolated muropeptide dimers stabilized over the same period of time. The results have led to the formulation a new model for the assembly of peptidoglycan into the cylindrical wall of B. megaterium by a monomer addition process. Single nascent glycan peptide strands form cross-linkages only with material at the inner surface of the wall. Maturation is a direct consequence of subsequent incorporation of further new glycan peptide strands, and there is no secondary cross-linking process. The initial distribution of muropeptides is constant. It follows that the final pattern of cross-linking in the wall is determined solely by, and can be forecast from, this repetitive pattern of incorporation. In a modified form, this model can also be applied to assembly of cell walls in rod-shaped gram-negative bacteria.

Bacillus megaterium

The neural basis for learning of simple motor skills.

The vestibulo-ocular reflex (VOR) is a simple movement that has been used to investigate the neural basis for motor learning in monkeys. The function of the VOR is to stabilize retinal images by generating smooth eye movements that are equal and opposite to each head movement. Learning occurs whenever image motion occurs persistently during head turns; as a result image stability is gradually restored. A hypothesis is proposed in which the output from the cerebellar cortex of the flocculus guides learning; the locus of learning is in the brain stem, in VOR pathways that are under inhibitory control from the flocculus. Other, parallel VOR pathways do not receive inputs from the flocculus and are not subject to learning. Similarities among the VOR and other motor systems suggest some organizing principles that may apply in many forms of motor learning.

Action Potentials

An improved aerosol generator.

An aerosolizer has been developed which automatically compensates for changes in the concentration and volume of a solution during aerosolization by adjustment of the temperature and pressure of the atomizing air jet. It represents the redesign of a generator previously used for short-term inhalation exposures (one-half to a few hours) where variability in solution concentration was not of great concern and solutions could be replenished daily. The stability of the original generator was quite inadequate, and it was not satisfactory for production of aerosols of constant physical characteristics over longer or repetitive time periods or where a minimum of manipulation is required--viz., for radioactive and other highly noxious materials. The redesigned aerosolizer should be valuable for long-term or repetitive use, since it requires no cleaning, merely refilling, and can 0e made as small or as large as experimental needs require. It should be particularly useful where correlations between the amount of deposition and aerosol characteristics are being studied.

Aerosol Propellants

Brain stem neurons in modified pathways for motor learning in the primate vestibulo-ocular reflex.

The vestibulo-ocular reflex (VOR) stabilizes retinal images by generating smooth eye movements that are equal in amplitude and opposite in direction to head turns. Whenever image motion occurs persistently during head turns, the VOR undergoes motor learning; as a result image stability is gradually restored. A group of brain stem neurons that are in the modified pathways has now been described. The neurons express changes in firing in association with motor learning in the VOR and receive monosynaptic inhibition from the flocculus of the cerebellum. The changes in firing have an appropriate magnitude and are expressed at the correct latency to account for the altered VOR. The response properties of the neurons point to their brain stem vestibular inputs for further investigation of the site of motor learning.

Action Potentials

The formation and metabolism of N-hydroxymethyl compounds--III. The metabolic conversion of N-methyl and N,N,-dimethylbenzamides to N-hydroxymethyl compounds.

The stability of metabolically-generated N-(hydroxymethyl) compounds was investigated using a series of N-methylbenzamides as model substrates. N-(Hydroxymethyl)-benzamide was characterized as a major metabolite of N-methylbenzamide in vitro, and was also identified as a urinary metabolite of N-methylbenzamide. N-(Hydroxymethyl) compounds were also found as metabolites of 4-chloro-N-methylbenzamide and 4-t-butyl-N-methylbenzamide in vitro. Thus substitution in the 4-position of the phenyl ring of derivatives of N-(hydroxymethyl)-benzamide did not affect their stability sufficiently to cause degradation to formaldehyde under the conditions used. N-(Hydroxymethyl)-N-methylbenzamide was identified as a metabolite of N,N-dimethylbenzamide in vitro. However, N-(hydroxymethyl)-N-methylbenzamide was less stable than N-(hydroxymethyl)-benzamide under alkaline conditions. Furthermore, N-(hydroxymethyl)-N-methylbenzamide, unlike N-(hydroxymethyl)-benzamide and its 4-substituted derivatives, was positive in the colorimetric assay for formaldehyde, presumably because of its degradation to produce formaldehyde. Thus substitution on the nitrogen atom which bears the methyl group in N-methylbenzamide markedly affected the stability of the N-methylol produced during oxidative metabolism. N-Formylbenzamide was identified as a metabolite of N-methylbenzamide in suspensions of mouse hepatocytes and also in vivo. The mechanism for its production probably involves the generation of N-(hydroxymethyl)-benzamide.

Animals

The latency of pathways containing the site of motor learning in the monkey vestibulo-ocular reflex.

The vestibulo-ocular reflex helps to stabilize retinal images by generating smooth eye movements that are equal to and opposite each rotatory head movement. It is well known that the reflex undergoes adaptive plasticity or "motor learning" whenever there is persistent image motion during head turns: the resulting changes in the reflex occur gradually and help to restore image stability. A new approach makes it possible to identify the pathways containing the site of motor learning according to their total latency in response to natural vestibular stimuli. The fastest pathways required 14 milliseconds to initiate a vestibulo-ocular reflex, but the site of motor learning was in pathways having latencies of at least 19 milliseconds.

Animals

Mitochondrial DNA heteroplasmy in Drosophila mauritiana.

Mitochondrial DNA extracted from an isofemale strain of Drosophila mauritiana (subgroup melanogaster) appeared to be heterogeneous in size. A short genome [S; 18,500 base pairs (bp)] and a longer one (L; 19,000 bp) coexist in the preparation. The additional 500 bp have been located within the A+T-rich region. Hpa I digest patterns suggest that the S genome may carry a duplication of a 500-bp sequence including an Hpa I site and that the L genome may carry a triplication of the same sequence. At the 30th generation of the isofemale strain, 60 female genotypes were examined individually. Half of the files were pure either for the S or the L DNA. The remaining 50% exhibited various degrees of heteroplasmy for the two DNA types. Among metazoan animals, this D. mauritiana strain offers an exceptional situation with regard to the number of individuals heterogeneous for mtDNA and the relative stability of heteroplasmy through generations.

Animals

Electronegativity of aromatic amines as a basis for the development of ground state inhibitors of lysyl oxidase.

Benzylamine derivatives containing para substituents of differing electronegativity as well as isomers of aminomethylpyridine have been assessed for their substrate and inhibitor potentials toward lysyl oxidase. Substituted benzylamines with increasingly electronegative para substituents had the lowest KI values and thus were the most effective inhibitors of the oxidation of elastin by lysyl oxidase. The kcat values for these compounds as substrates of lysyl oxidase were also reduced with increasingly electronegative para substituents. Both the Dkcat and D(kcat/Km) kinetic isotope effects decreased with increasingly electronegative p-substituents in [alpha, alpha'-2H]benzylamines. In contrast, there was no Dkcat solvent isotope effect with [2H] H2O while the D(kcat/Km) solvent isotope effect tended to increase with increasingly electronegative p-substituents. These results are consistent with the stabilization of an enzyme-generated substrate carbanion and thus the retardation of substrate oxidation by electronegative substituents. Such ground state stabilization thus can result in compounds with increased potential for the inhibition of the oxidation of protein substrates of lysyl oxidase.

Amino Acid Oxidoreductases

Activated oxygen species and oxidation of food constituents.

Activated oxygen species which may be important in initiating oxidative changes in foods include singlet oxygen, hydroxyl radical, ozone, superoxide anion (perhydroxyl radical at low pH), and hydrogen peroxide. Chemical and enzymic reactions known to occur in biological materials can generate singlet oxygen, hydroxyl radical, superoxide anion, and hydrogen peroxide. Ozone is primarily a product of photoreactions in polluted air. Reactions involving singlet oxygen, hydroxyl radical, and ozone with food constituents can ultimately yield peroxides which decompose to initiate oxidative chain reactions. Superoxide anion and hydrogen peroxide are relatively inert toward organic molecules but can decompose to produce the more reactive singlet oxygen and hydroxyl radical. Inhibition of reactions initiated by reactive oxygen species in foods should be very important in preserving the oxidative stability of foods. The generation, detection, measurement, reaction, and inhibition of reactions of active oxygen species are surveyed in this review.

Amino Acids

The maintenance of genetic variability in two-locus models of stabilizing selection.

The maintenance of genetic variability at two diallelic loci under stabilizing selection is investigated. Generations are discrete and nonoverlapping; mating is random; mutation and random genetic drift are absent; selection operates only through viability differences. The determination of the genotypic values is purely additive. The fitness function has its optimum at the value of the double heterozygote and decreases monotonically and symmetrically from its optimum, but is otherwise arbitrary. The resulting fitness scheme is identical to the symmetric viability model. Linkage disequilibrium is neglected, but the results are otherwise exact. Explicit formulas are found for all the equilibria, and explicit conditions are derived fro their existence and stability. A complete classification of the six possible global convergence patterns is presented. In addition to the symmetric equilibrium (with gene frequency 1/2 at both loci), a pair of unsymmetric equilibria may exist; the latter are usually, but not always, unstable. If the ratio of the effect of the major locus to that of the minor one exceeds a critical value, both loci will be stably polymorphic. If selection is weak at the minor locus, the more rapidly the fitness function decreases near the optimum, the lower is this critical value; for rapidly decreasing fitness functions, the critical value is close to one. If the fitness function is smooth at the optimum, then a stable polymorphism exists at both loci only if selection is strong at the major locus.

Chromosome Mapping

Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres.

Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.

Adaptation, Biological

Studies on the stability of VIII:C during the manufacture of a factor VIII concentrate for clinical use.

The stability of VIII:C was investigated by monitoring samples taken at different points from a routine process for the manufacture of factor VIII concentrate and by examining the stabilising influence of a number of product formulations. Loss of VIII:C over process-finishing procedures (formulation, 0.22 micron filtration, dispensing) was associated with a citrate-induced inactivation which could be prevented by controlling the ionised calcium concentration of the solution. These results were obtained using a one-stage clotting assay but were not observed using a two-stage assay. No evidence for activation was found in vitro (e.g. by FPA generation and VIII:C stability) and the yield increase suggested by the one-stage assay was supported by results from a controlled clinical evaluation.

Antigens

Dipole tracing in childhood epilepsy with special reference to rolandic epilepsy.

To assess the clinical applicability of dipole tracing in childhood epilepsy, the location and stability of electric source generator of focal spikes seen in EEG of epileptic children were investigated using this method. The patients were divided into 3 groups; benign childhood epilepsy with centrotemporal spikes (BCECS, Group A, n = 14), other types of epilepsy with centrotemporal spikes (Group B, n = 15) and epilepsy with focal spikes in other areas (Group C, n = 13). The spike dipole in each group was analyzed using dipole tracing method. The following results were obtained. (1) The spikes of BCECS were characterized by constantly stable dipoles, compared to those of the other types of childhood epilepsy. The spikes of epileptic children with mental retardation mostly lacked the stability of dipoles. These seemed to suggest that the stability of dipoles was closely related to the prognosis and pathophysiology of epilepsy. (2) The dipoles of BCECS were localized strictly in the Rolandic area. Dipole tracing from EEG spikes was considered to contribute to the elucidation of the pathophysiology of childhood epilepsy.

Adolescent