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PubMed1985

Homogeneously staining regions (HSRs) of a rat hepatoma cell line are not early replicating.

The rat hepatoma cell line H4-IIE-C3 (H4) has homogeneously staining regions (HSRs) which contain multiple, tandemly repeated copies of ribosomal RNA (rRNA) genes. We determined the time of replication of the DNA within these HSRs autoradiographically after incorporation of [3H]thymidine and by Hoechst 33258 and Giemsa staining after 5-bromodeoxyuridine (5-BrdU) incorporation. The DNA within the H4 HSRs is not early replicating, unlike that in other HSRs. It begins replicating later than much of the other nuclear DNA, continues replicating throughout most of the S phase, and is completed 1-2 h before mitosis.

Animals↗
PubMed2001

Is mixed effects modeling or naïve pooled data analysis preferred for the interpretation of single sample per subject toxicokinetic data?

The purpose of this study was to evaluate whether mixed effects modeling (MEM) performs better than either noncompartmental or compartmental naïve pooled data (NPD) analysis for the interpretation of single sample per subject pharmacokinetic (PK) data. Using PK parameters determined during a toxicokinetic study in rats, we simulated data sets that might emerge from similar experiments. Data sets were simulated with varying numbers of animals at each sampling time (4-48) and the number of samples taken (1-3) from each individual. Each data set was replicated 50 times and analyzed using several variations of MEM that differed in the assumptions made regarding intraindividual error, NPD, and a graphical noncompartmental method. These analyses attempted to retrieve the underlying parameter and covariate effect values. We compared these analysis methods with respect to how well the underlying values were retrieved. All analysis methods performed poorly with single sample per subject data but MEM gave less biased estimates under the simulated conditions used here. MEM performance increased when covariate effects were sought in the analysis compared with analyses seeking only PK parameters. Decreasing the number of animals used per sampling time from 48 to 16 did not influence the quality of parameter estimates but further reductions (< 16 animals per sampling time) resulted in a reduced proportion of acceptable estimates. Parameter estimate quality improved and worsened with MEM and NPD, respectively, when additional samples were obtained from each individual. Assumptions made regarding the magnitude of intraindividual error were unimportant with single sample per subject data but influenced parameter estimates if more samples were obtained from each individual. MEM is preferable to both NPD and noncompartmental approaches for the analysis of single sample per subject data but even with MEM estimates of clearance are often biased.

Animals↗
PubMed1994

The configuration of DNA replication sites within the Trypanosoma brucei kinetoplast.

The kinetoplast is a concatenated network of circular DNA molecules found in the mitochondrion of many trypanosomes. This mass of DNA is replicated in a discrete "S" phase in the cell cycle. We have tracked the incorporation of the thymidine analogue 5-bromodeoxyuridine into newly replicated DNA by immunofluorescence and novel immunogold labeling procedures. This has allowed the detection of particular sites of replicated DNA in the replicating and segregating kinetoplast. These studies provide a new method for observing kinetoplast DNA (kDNA) replication patterns at high resolution. The techniques reveal that initially the pattern of replicated DNA is antipodal and can be detected both on isolated complexes and in replicating kDNA in vivo. In Trypanosoma brucei the opposing edges of replicating kDNA never extend around the complete circumference of the network, as seen in other kinetoplastids. Furthermore, crescent-shaped labeling patterns are formed which give way to labeling of most of the replicating kDNA except the characteristic midzone. The configuration of these sites of replicated DNA molecules is different to previous studies on organisms such as Crithidia fasciculata, suggesting differences in the timing of replication of mini and maxicircles and/or organization of the replicative apparatus in the kinetoplast of the African trypanosome.

Animals↗
PubMed2005

Comparison of inorganic and organic selenium sources for broilers.

An experiment was conducted to compare the effects of organic and inorganic sources of Se on growth performance, carcass traits, breast and plasma Se concentrations, and plasma glutathione peroxidase (pGPX3) activity in broilers. Broiler chicks were sexed on d 0 and within sex, randomly allotted to dietary treatment. Average initial and final BW of the broilers were 47 and 2,684 g, and the experiment lasted 49 d. A 3-phase feeding program similar to industry recommendations was used, and the basal diets for each phase were corn-soybean meal based. For each growth phase, the basal diet was supplemented with 0 (control) or 0.30 ppm Se from sodium selenite (SS) or Se-enriched yeast (SY). Each treatment was replicated 7 times (4 pens of males and 3 pens of females) with 50 male or 55 female broilers per replicate. Daily gain, feed intake, gain:feed, eviscerated and chill weights, carcass yield, breast weight, and moisture loss from the breast were not affected (P > 0.05) by Se supplementation. Dietary supplementation with SY increased (P < 0.05) muscle and plasma Se concentrations compared with broilers fed the control diet or the diet with SS. Plasma GPX3 activity was not affected (P > 0.05) by Se source or concentration. The results from this experiment indicate that organic Se increases tissue Se concentration, but it does not affect growth performance, carcass traits, or pGPX3 activity compared with inorganic Se.

Animal Nutritional Physiological Phenomena↗
PubMed1971

Contrast and induction in rats on multiple schedules.

Eight rats were trained on a variable-interval schedule in the presence of a light (Phase I). Responding was then extinguished in the presence of darkness that alternated with the light (Phase II). Reinforcement was then introduced in the presence of darkness (Phase III). Several rats were then returned to the condition of Phase II (Phase IV) and then to that of Phase III (Phase V). The responding of most rats showed clear behavioral contrast in Phase II-i.e., an increase in responding in the presence of the light. When, for three rats, Phase III was introduced early after the occurrence of positive contrast, either positive induction occurred, i.e., an increase in responding in the presence of the light, or there was little change. Negative contrast did not occur. It was further shown that positive contrast dissipates over time, thus replicating a result previously obtained with pigeons and that the positive induction effect seems also to dissipate over time. The introduction of reinforcement in the presence of darkness (Phases III and V) after the dissipation of positive contrast seemed to have little consistent effect.

Journal Article↗
PubMed1982

Cytogenetic replication studies on murine T-cell leukemias with special consideration to chromosome 15.

Chromosomal replication was studied by means of the BrdU-Höchst-Giemsa-technique in three minute T-cell leukemias with special regard to chromosome 15. In all the three leukemic cell lines the normally early replicating band 15 E was undetectable whereas late replication in this region is completely unaltered. Furthermore, R-banding, the structural homologue of early replication banding, remains unchanged. This observation is interpreted as a shift in the time point of replication during the S-phase of region 15 E, though the exact timing of replication of this region in tumor chromosomes remains unresolved.

Animals↗
PubMed1977

Features of the structure of replicating and non-replicating chromatin in chicken erythroblasts.

The digestion by DNAase I of DNA synthesised by isolated chicken erythroblasts was examined in isolated nuclei. It was found that newly synthesised DNA was susceptible to DNAase I but matured to a relatively resistant form with increasing time after replication as observed in mammalian systems. The presence of trypsin in the digestion exposed all of the DNA to DNAase I action. Examination of the digestion products showed that the newly replicated DNA differed little from the more mature form in the structure of the DNA-protein complex but that the difference in susceptibility was probably a result of a differential rate of access of the DNAase to the new and old DNA.

Animals↗
PubMed1987

Order of gene replication in Caulobacter crescentus; use of in vivo labeled genomic DNA as a probe.

Two methods for determining the time of gene replication in Caulobacter crescentus using a temperature sensitive DNA synthesis mutant to synchronize chromosome replication are described. Swarmer cells, blocked before DNA initiation at 37 degrees C, initiate chromosome replication within 2 min after releasing the temperature block in 32P-orthophosphate medium, as indicated by the appearance of a small number of unique genomic DNA fragments. The time at which a given chromosome segment replicates was determined by isolating genomic DNA from cells labeled for progressively longer times during the S period of the cell cycle and hybridizing the probes to cloned C. crescentus genes. The time of replication of genetically mapped Tn5 insertions was determined by preparing DNA from the Tn5 insertion mutants that had been labeled with 32P in similar experiments and hybridizing it to lambda::Tn5 DNA. These results furnish the first correlation between the order of chromosome replication and the genetic map of C. crescentus. They also show that the times of replication and expression of the hook protein and the flagellin genes, which require DNA synthesis for their transcription, both occur near mid-S phase.

Bacterial Proteins↗
PubMed1989

Regrowth of arterial endothelium. Denudation with minimal trauma leads to complete endothelial cell regrowth.

Endothelial regeneration in the rat carotid artery was investigated using two different techniques of denudation. With balloon catheter denudation, medial cell death occurred, and endothelial regrowth stopped after several weeks, leaving a large area devoid of endothelium. After denudation with a new technique that removed the endothelium without damaging the media complete endothelial regrowth was achieved. Acutely after this denudation, large platelet thrombi were present on the subendothelial surface of vessels denuded with the filament loop. In contrast, balloon catheter denuded arteries showed only a platelet monolayer on their luminal surface. Within the first few weeks after denudation with either technique the regenerating endothelial cells stained strongly for basic fibroblast growth factor. At later times when replication of endothelium had stopped, the balloon catheter denuded vessels did not stain with this antibody. After filament denudation endothelial cell replication remained high until regrowth was complete and intensive staining was observed in the regenerating endothelial cells at all times. No differences were seen in staining of smooth muscle cells for transforming growth factor-beta and fibronectin in either set of denuded vessels. Both groups showed transforming growth factor-beta to be located in the developing intima and especially on the apical surface of luminal smooth muscle cells. The surface of these luminal smooth muscle cells also stained with antibody to fibronectin. These data demonstrate that total regrowth of endothelium can occur over large denuded areas despite the presence of transforming growth factor-beta and fibronectin on these surfaces. Furthermore the ability of these endothelial cells to proliferate would appear to be dependent on the presence of basic fibroblast growth factor and on the severity of the trauma induced by denudation.

Animals↗
PubMed1975

Regulation of DNA replication on subchromosomal units of mammalian cells.

The regulation of DNA replication at a subchromosomal level in mammalian cells has been investigated. DNA fiber autoradiographs were prepared from mouse L-929 cells pulse labeled with (3H)thymidine. Initiation events and subsequent chain growth occurring over short stretches (up to three replication units in length) of chromosomal DNA were analyzed. The results show that adjacent units usually initiate replication synchronously and that this synchrony is related to the proximity of initiation sites. In addition, adjacent units are of similar size and the rates of replication fork progression within units and on adjacent units are similar. The rate of fork progression increases with increasing replication unit size. Finally, no evidence for fixed termination sites for the units has been found. These observations suggest that despite large variations in size of replication units, timing of initiation events, and rates of fork progression found in chromosomal DNA as a whole, these processes are closely regulated within subchromosomal clusters of active replication units.

Animals↗
PubMed2001

Intraspecific competition in populations of Helix aspersa with different histories of exposure to lead.

A range of invertebrates have become adapted to certain toxic metals, such that, in the presence of the contaminant, some measure of their performance, typically growth or reproduction, is superior to that of an unexposed population. Under such a toxic stress, a population with a history of exposure might outperform a naïve population in competition for limited resources. This study compared the shell growth of laboratory-bred juveniles from six populations of Helix aspersa with different histories of exposure to Pb. In 10 trials using various combinations of two populations, the snails competed for a limited supply of food that contained either no Pb or 500 micrograms/g-1 Pb, for 98 days. Each trial consisted of 10 juveniles, five from each population and was replicated four times. Nearly all of the food provided was consumed quickly after presentation. The total amount of shell growth within each replicate (the sum of the mean growth of the two populations) was highly consistent between trials so that the total amount of shell built was limited by food availability. The presence of Pb in the diet caused no measurable depression of shell growth and exposure history did not appear to confer any competitive advantage or disadvantage in any of the trials. One population consistently grew faster than its competitors in every trial of which it was a part. Shell growth tended to be greater in smaller juveniles. Snail activity is known to be inhibited at high densities and this may have contributed to the lower incremental growth in individuals kept at the higher densities. The competitive advantage enjoyed by one population may be primarily determined by their activity or perhaps their Ca metabolism.

Adaptation, Physiological↗
PubMed1982

Establishment of infection by spleen necrosis virus: inhibition in stationary cells and the role of secondary infection.

The relationship of two early events in the establishment of infection by avian retroviruses, the inhibition of viral DNA synthesis in stationary avian cells and the secondary infection which occurs after infection of replicating cells, was investigated. When neutralizing antibody to spleen necrosis virus was used to prevent secondary infection, the amount of unintegrated linear spleen necrosis virus DNA detected was much lower in infected stationary cells than in infected replicating cells. The amount of unintegrated linear spleen necrosis virus DNA in stationary cells was less than one copy per cell even at high multiplicities of infection. Viral DNA synthesis resumed after stimulation of the cells to replicate. The time of this viral DNA synthesis was closely correlated with renewed cellular DNA synthesis. In addition, blocking secondary infection of replicating cells prevented the rate of virus production from reaching the high levels usually associated with a normal productive infection by SNV. Virus production increased if secondary infection was allowed. However, this rise in virus production was not proportional to the amounts of viral DNA integrated after secondary infection.

Alpharetrovirus↗
PubMed1995

Correlation of virus replication, cytokine (TNF-alpha and IL-1) producing cells, neuronal necrosis and inflammation after intranasal infection of mice with herpes simplex virus strains of different virulence.

The number of TNF-alpha and IL-1 beta producing cells was investigated during the acute replication phase of herpes simplex virus (HSV) in trigeminal ganglia after intranasal infection with strains of different virulence. The highly virulent strain WAL replicated strongly and induced many cytokine producing cells early in the ganglia. The low virulent strain HFEM replicated less, only few cytokine producing cells were detected late. The thymidine-kinase negative (TK-) virus 1301 did not replicate but produced some lymphocytic inflammation. The higher the virulence of strains of HSV-1 or -2 was, the stronger was the extent of histopathological lesions; moreover, a dissociation in time between replication and cellular reaction (granulocytic and lymphocytic) could be observed after infection with strains HFEM and TK- virus 1301. CD4 and CD8 positive cells could be detected mainly at the rim of necrotic areas, TNF-alpha and IL-1 beta producing cells, however, were scattered throughout the ganglia.

Administration, Intranasal↗
PubMed1989

Promoter occlusion prevents transcription of adenovirus polypeptide IX mRNA until after DNA replication.

The left end of the adenovirus genome is arranged such that the polypeptide IX gene is 'buried' (entirely contained) within the E1B transcription unit. The E1B gene is transcribed actively early in infection while, in contrast, IX gene transcription only occurs after DNA replication. Using recombinant plasmid constructs and recombinant viruses, we have found that the nested arrangement of the IX gene prevents its transcription. The experiments show that E1B transcription across the IX promoter inhibits IX gene expression early in infection, and yet, the 21-kD E1B protein activates the IX gene. IX mRNA synthesis occurs in the absence of DNA replication when the E1A gene and E1B promoter are absent, but only when the 21-kD E1B protein is present in trans. Our results indicate that during the adenovirus infectious cycle, the only templates on which IX transcription can be activated are newly replicated templates not committed to E1B transcription. This situation may be a model for genes that are activated specifically at the time of replication.

Adenoviridae↗
PubMed1992

Temporal order of DNA replication in the H-2 major histocompatibility complex of the mouse.

As an approach to mapping replicons in an extended chromosomal region, the temporal order of DNA replication was analyzed in the murine major histocompatibility gene complex (MHC). Replicating DNA from T-lymphoma and myelomonocyte cell lines was density labeled with bromodeoxyuridine and extracted from cells which had been fractionated into different stages of S phase by centrifugal elutriation. The replicating DNA from each fraction of S phase was separated from nonreplicating DNA on density gradients, blotted, and hybridized with 34 specific MHC probes. The earliest replication occurred in the vicinity of transcribed genes K, HAM1 and HAM2, RD, B144, D, L, T18, and T3. The temporal order of replication of groups of DNA segments suggests the location of five or six replicons within the H-2 complex, some of which appear to be either unidirectional or markedly asymmetric. The rates of replication through each of these apparent replicons appear to be similar. The TL region of the S49.1 T-lymphoma cells, which contains at least three transcribed genes, replicates earlier than the inactive TL region of WEHI-3 myelomonocytic cells. These results provide further evidence of a relationship between transcription and the initiation of DNA replication in mammalian cells. The mouse MHC examined in this study is the largest chromosomal region (> 2,000 kb) measured for timing of replication to date.

Animals↗
PubMed1997

Developmental regulation of DNA replication: replication fork barriers and programmed gene amplification in Tetrahymena thermophila.

The palindromic Tetrahymena ribosomal DNA (rDNA) minichromosome is amplified 10,000-fold during development. Subsequent vegetative replication is cell cycle regulated. rDNA replication differs fundamentally in cycling vegetative and nondividing amplifying cells. Using two-dimensional gel electrophoresis, we show for the first time that replication origins that direct gene amplification also function in normal dividing cells. Two classes of amplification intermediates were identified. The first class is indistinguishable from vegetative rDNA, initiating in just one of the two 5' nontranscribed spacer (NTS) copies in the rDNA palindrome at either of two closely spaced origins. Thus, these origins are active throughout the life cycle and their regulation changes at different developmental stages. The second, novel class of amplification intermediates is generated by multiple initiation events. Intermediates with mass greater than fully replicated DNA were observed, suggesting that onionskin replication occurs at this stage. Unlike amplified rDNA in Xenopus laevis, the novel Tetrahymena species are not produced by random initiation; replication also initiates in the 5' NTS. Surprisingly, a replication fork barrier which is activated only in these amplifying molecules blocks the progression of forks near the center of the palindrome. Whereas barriers have been previously described, this is the first instance in which programmed regulation of replication fork progression has been demonstrated in a eukaryote.

Animals↗
PubMed1992

[Evolution and ecological changes of animal viruses].

Although the origin of viruses has not yet been clarified, definite differences in evolutionary patterns have been found among RNA. Retro and DNA viruses. These differences are reflected in infectious diseases. RNA viruses, which have RNA in their genome, replicate many times over in cells within a short period of time, destroying the host cells and causing an acute infection. As the error frequency of RNA replicase enzymes is high, the rate of evolution of RNA viruses is very rapid. Retroviruses also contain RNA as their genome, but the genome RNA is reversely transcribed to the DNA in nuclei and then incorporated into the host chromosome to replicate. The error frequency of reverse transcriptase is also high, and therefore mutations easily occur as well. The transcribed DNA is integrated into host DNA in the nucleus, and it remains in the integrated state for human entire life time, causing chronic disease or developing malignant tumors. As DNA viruses except poxviruses replicate inside the cell nucleus and the error frequency of DNA polymerase is low, the speed of mutation and the degree of resulting diversity are lower than those in the case of the RNA virus. DNA viruses tend to stay inside the body for long periods of time and easily become latent. In this paper, I shall discuss 1) the nature of viruses, 2) the origin of viruses, 3) mutation and recombination, 4) diversity of RNA viruses, 5) quickly changing viral diseases, 6) eradicated viral diseases, 7) chronic and malignant diseases, and 8) control of viral diseases.

Biological Evolution↗