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PubMed1999

The pattern of replication at a human telomeric region (16p13.3): its relationship to chromosome structure and gene expression.

We have studied replication throughout 325 kb of the telomeric region of a human chromosome (16p13.3) and related the findings to various aspects of chromosome structure and function (DNA sequence organization, nuclease-hypersensitive sites, nuclear matrix attachment sites, patterns of methylation and gene expression). The GC-rich isochore lying adjacent to the telomere, which contains the alpha-globin locus and many widely expressed genes, replicates early in the cell cycle regardless of the pattern of gene expression. In subtelomeric DNA, replication occurs later in the cell cycle and the most telomeric region (20 kb) is late replicating. Juxtaposition of early replicating DNA next to the telomere causes it to replicate later in S-phase. Analysis of the timing of replication in chromosomes with deletions, or in transgenes containing various segments of this telomeric region, suggests that there are no critical origins or zones that initiate replication, rather the pattern of replication appears to be related to the underlying chromatin structure which may restrict or facilitate access to multiple, redundant origins. These results contrast with the pattern of replication at the human beta-globin locus and this may similarly reflect the different chromosomal environments containing these gene clusters.

Animals↗
PubMed1994

DNA replication analysis of FMR1, XIST, and factor 8C loci by FISH shows nontranscribed X-linked genes replicate late.

The relationship between the transcriptional state of a locus and the time when it replicates during DNA synthesis is increasingly apparent. Active autosomal genes tend to replicate early, whereas inactive ones are more permissive and frequently replicate later. Although the inactive X chromosome replicates later than its active homologue, little is known about the replication of X-linked genes. We have used FISH to examine the replication of loci on the active X chromosome that are not transcribed, either because the tissue analyzed was not the expressing tissue (F8C), because the locus is silent on all active X chromosomes (XIST), or because it has been mutated by expansion and methylation of a CpG island (FMR1). In this assay, an unreplicated locus is characterized by a single hybridization signal, and a replicated locus is characterized by a doublet hybridization signal. The percentage of doublets is used as a measure of relative time of replication in S phase. The validity of this approach has been established elsewhere, since results compare favorably with those obtained using traditional methods for studying DNA replication. Our results show that the FMR1 gene replicates relatively later in fragile X (fraX) males with the full mutation than in normal males, irrespective of the probe used. The F8C locus is late replicating in both normal and fraX males and replicates at nearly the same time on active and inactive X in females. The XIST locus replicates late in all the males studied and asynchronously in female cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

Cell-cycle-specific initiation of replication.

The following characteristics are relevant when replication of chromosomes and plasmids is discussed in relation to the cell cycle: the timing or replication, the selection of molecules for replication, and the coordination of multiple initiation events within a single cell cycle. Several fundamentally different methods have been used to study these processes: Meselson-Stahl density-shift experiments, experiments with the so-called 'baby machine', sorting of cells according to size, and flow cytometry. The evidence for precise timing and co-ordination of chromosome replication in Escherichia coli is overwhelming. Similarly, the high-copy-number plasmid ColE1 and the low-copy-number plasmids R1/R100 without any doubt replicate randomly throughout the cell cycle. Data about the low-copy-number plasmids F and P1 are conflicting. This calls for new types of experiments and for a better understanding of how these plasmids control their replication and partitioning.

Bacteriological Techniques↗
PubMed1992

Identification of skeletal muscle precursor cells in vivo by use of MyoD1 and myogenin probes.

The activation of mononuclear muscle precursor cells after crush injury to mouse tibialis anterior muscles was monitored in vivo by in situ hybridization with MyoD1 and myogenin probes. These genes are early markers of skeletal muscle differentiation and have been extensively studied in vitro. The role in vivo of these regulatory proteins during myogenesis of mature muscle has not been studied previously. MyoD1 and myogenin mRNA were present in occasional mononuclear cells of uninjured muscle. Increased MyoD1 and myogenin mRNA sequences in mononuclear cells were detected as early as 6 h after injury, peaked between 24 and 48 h, and thereafter declined to pre-injury levels at about 8 days. The mRNAs were detected in mononuclear cells throughout the muscle, with the majority of cells located some distance from the site of crush injury. The presence of MyoD1 and myogenin mRNA at 6 to 48 h indicates that transcription of these genes is occurring at the same time as replication of muscle precursor cells in vivo. At no time were significant levels of mRNA for these genes detected in myotubes. MyoD1 and myogenin provide precise markers for the very early identification and study of mononuclear skeletal muscle precursor cells in muscle regenerating in vivo.

Animals↗
PubMed1979

Mental travel: some reservations.

Two experiments were conducted to assess the extent of potential experimental demand characteristics inherent in the image-scanning paradigm. The results of the first "mental travel" experiment that pitted verbal versus imagery coding showed that (a) the positive correlation between physical distance and reaction time was replicated, and (b) when given a choice, subjects' reaction times varied as a function of verbal codes rather than imagery. To isolate the effects due to demand constraints from those produced by mode dominance, a nonexperiment in which subjects received only a description of the image-scanning procedure was conducted. Results demonstrated that subjects were capable of predicting the reaction time results for both verbal and imagery codes. The presence of experimental demand in the image-scanning paradigm necessitates caution when structural interpretations of visual images are considered.

Distance Perception↗
PubMedDate not supplied

Repeatability of replicate breath alcohol measurements collected in short time intervals.

The effect of short time interval sampling between replicate breath alcohol samples has been investigated. The results from 10 samples, which were collected approximately one minute apart from eight individuals and approximately 20 seconds apart from one individual, were evaluated by simple linear regression. The regression coefficient (slope) and its standard error were evaluated for the presence of any trend in alcohol depletion. Other statistical analyses were also included in this assessment. All nine subjects had linear regression coefficients for the end-expiratory results that were not significantly different from zero (P > 0.05). In view of the respiratory physiology, there does not appear to be any measurable depletion of breath alcohol concentration due to sampling intervals as short as one minute.

Alcohol Drinking↗
PubMed2004

Porcine adenovirus type 3 E1 transcriptional control region contains a bifunctional regulatory element.

We identified a bifunctional regulatory element located between nt 374 and 431 upstream of TATA box of porcine adenovirus (PAV) 3 E1A promoter. Deletion of the element dramatically reduced the steady-state level of E1A mRNA, but increased that of E1B, which lies immediately downstream of E1A. The mutant virus displayed defective replication at early times of infection, but replicated nearly as efficiently as wild-type PAV-3 at late times of infection. This defect was complemented with coinfecting wild-type virus in a mixed infection. The results indicated that the upstream activation sequences (UAS) of E1A overlap the upstream repression sequences (URS) of E1B, although both transcription units are transcribed from different promoters.

Adenovirus E1A Proteins↗
PubMed2001

Comparison of number of Streptococcus uberis calculated on a volume or weight basis in sand and sawdust bedding.

OBJECTIVE: To determine a method for comparing counts of Streptococcus uberis in sand and sawdust and account for the influence of weight or volume of the bedding material. SAMPLE POPULATION: 2 sources of kiln-dried sawdust and 2 sources of washed sand. PROCEDURES: Sterilized bedding material (100 ml) was weighed and uniformly distributed in an aluminum pan. Each sterilized bedding material was inoculated with a mean of 3.6 X 10(6) (experiment 1) or 2.4 X 10(7) (experiment 2) colony-forming units (CFU) of S uberis/ml of bedding material. Without allowing time for replication of S uberis, inoculated bedding materials were washed with sterile saline (0.9% NaCl) solution. A 200-ml aliquot of wash solution was serially diluted up to 2,500 times with additional saline solution and inoculated on plates containing tryptose agar with 5% sheep blood. After incubation for 48 hours, number of CFU of S uberis was counted. This procedure was replicated 19 and 16 times for each bedding material in experiments 1 and 2, respectively. RESULTS: Evaluation of Bonferroni 95% confidence intervals revealed significant differences for counts of S uberis calculated on a weight basis between sand and sawdust. CONCLUSIONS AND CLINICAL RELEVANCE: Comparison of counts of S uberis determined on a volume basis for sand and sawdust accentuates to a lesser degree the weight difference of the bedding materials and ensures a more appropriate comparison of number of S uberis.

Animals↗
PubMed1986

Inhibition of SV40 DNA replication by benzo[a]pyrene diol epoxide adducts: two recovery modes.

Anti-benzo[a]pyrene diol epoxide (BPDE) adducts produced in vitro in SV40 initially inhibit SV40 DNA replication in vivo, in cells unexposed to BPDE. A single adduct in a replicon is probably sufficient to block DNA replication. The recovery process appears to begin immediately after infection. The rate of recovery of replicative capacity is inversely related to the initial adduct number. Holding the infected cells temporarily under conditions that prevent viral DNA replication results subsequently in increased recovery, proportional to the holding time. The mechanism of recovery appears to be constitutive and prereplicative. In addition, there is a second mode of recovery which is induced by pretreatment of the host cells with BPDE before infection. The effect of pretreatment is similar to that of extending the holding time before replication: the first molecules begin to replicate earlier but the subsequent rate of recovery is unchanged. The induced mechanism may be either a limited stoichiometric repair process or a slow replicative bypass.

Animals↗
PubMed2000

Antivirals other than for HIV therapy.

This review concentrates on drugs directed at viruses other than HIV and does not include anti-HIV drugs. Many antivirals are nucleoside analogues, although new classes of enzyme inhibitors are being developed for treatment of HIV (proteases) and enteroviruses. Antisense drugs and receptor blockers have recently been approved. Regardless of mechanism, antivirals are predominantly virustatic, not virucidal, and usually require help from the host immune system to either completely eliminate pathogens (e.g., influenza) or to provide sufficient immune surveillance to prevent a latent pathogen from reactivating (e.g., the herpesviruses). Viruses by nature are intracellular pathogens, using the host cell to produce progeny. Often the viral pathogen uses the host cell machinery or enzyme system to facilitate replication. At times the virus usurps nearly the entire intracellular system for replication and may shut down all functional host cell output for host-determined products. Because of the intracellular nature of viruses and because viruses use many "normal" host cell factors, functions, and systems for replication, antivirals can have notable toxicities to host cells. As antivirals inhibit viral activity in the viral-infected host cells (these encompass a minority of the total host cell numbers), they may also negatively affect functions in the virus-uninfected host cells. These alterations may be biochemical, detected only if sought specifically, or clinically obvious toxicities. Either may limit the use of some antivirals to severe or life-threatening situations.

Antiviral Agents↗
PubMed1999

Normal human telomeres are not late replicating.

Telomeres in yeast are late replicating. Genes placed next to telomeres in yeast can be repressed (telomere positional effects), leading to the hypothesis that telomeres may be heterochromatic and may control the expression of subtelomeric genes. In addition, yeast telomeres are processed to have a transient long overhang at the end of S phase. The applicability of the yeast data to human biology was examined by determining the timing of telomere replication and processing in normal human diploid fibroblasts. Telomeres were purified from synchronized cells that had been labeled with 5-bromodeoxyuridine (BrdU) at hourly intervals, and the fraction of labeled telomeres was analyzed by retrieval with anti-BrdU antibodies. We determined that normal human telomeres replicate throughout S phase rather than being very late replicating. Furthermore, the overall timing of replication was unaffected by telomere length in young versus old cells or cells whose telomeres had been elongated following transfection with the catalytic subunit of telomerase. Finally, the asymmetry in the length of the G-rich overhang in daughter telomeres produced by leading versus lagging strand synthesis was shown to be established within 1 h of telomere replication, indicating there is no significant delay between synthesis and the processing events that contribute to the establishment of asymmetric overhangs. Therefore, the timings of replication and processing of human telomeres are very different from those of yeast.

Base Composition↗
PubMed1990

DNA contents of replication without DNA density labeling.

A new method for determining the timing of DNA replication in specific regions of the mammalian genome without the use of DNA density labeling and DNA density centrifugation is described. The method is based on determination of average relative DNA copy numbers in specific genomic regions as cells progress through S phase, and "time of replication" for a specific region is described in terms of the cell's DNA content when the region is replicated. DNA is isolated from synchronized populations of G1 and S phase cells, it is slot-blotted at the same DNA concentration(s) for each population, and it is hybridized with 32P-labeled DNA probes that are specific to the regions of interest. Quantitation of the slot blot autoradiograms and flow cytometric analysis allows determination of (a) average relative DNA copy numbers for the regions of interest in synchronized cell populations, and (b) the average total DNA content in each population of synchronized cells. This information and the flow cytometry histograms are then used to calculate the cellular DNA content at which each region of interest is replicated. The results have a precision of less than or equal to +/- 10% of S phase for Chinese hamster (line CHO) rhodopsin, metallothionein II, the 5'-end of dihydrofolate reductase, the telomeric repeated sequence, pHuR-093 (also located near the centromeres in CHO chromosomes), and the c-Ki-ras family.

Cell Cycle↗
PubMed2005

Efficacy of either a single or split treatment of PGF2alpha after a 14 day melengestrol acetate treatment to synchronize estrus and induce luteolysis in Bos indicus x Bos taurus heifers.

Two experiments evaluated a modified delivery of prostaglandin F2alpha (PGF2alpha) after a melengestrol acetate (MGA) treatment in Angus and Bos indicus x Bos taurus (BI) heifers. Experiment 1 was replicated three times with yearling BI heifers (n = 695). Heifers received MGA (0.5 mg head(-1) day(-1)) for 14 days. In Replications 1 and 2, heifers received either 25 mg of PGF2alpha im 19 days after MGA (single) or 12.5 mg of PGF2alpha im 19 and 20 days after MGA (split). In Replication 3, heifers received the same treatments, with PGF2alpha initiated either 18 or 19 days after MGA. Estrus was detected for 72 h after PGF2alpha, with AI commencing 8-12 h after a detected estrus. Heifers not observed in estrus by 72 h were timed-AI concomitant with GnRH (100 microg im). Heifers from Replication 2 (n = 146) had blood samples collected at the initial PGF2alpha and at timed-AI to determine corpus luteum (CL) regression by evaluating plasma progesterone concentrations. The interval from MGA withdrawal to PGF2alpha did not have a significant effect on any variable in Replication 3 and there were no treatment by replication effects for any variables, therefore data were pooled. Modifying the PGF2alpha treatment from a single treatment to two treatments on consecutive days increased (P < 0.05) 72 h estrous response (43.2% versus 50.1%), timed-AI (23.9% versus 33.5%) and total-AI pregnancy rates (34.5% versus 42.5%), and CL regression (79.1% versus 92.5%), respectively. In Experiment 2, yearling Angus (n = 66) and 2-year-old BI (n = 68) heifers were synchronized as per Experiment 1 (with the initial PGF2alpha 19 days after MGA). Neither breed nor PGF2alpha treatment effected (P > 0.05) 72 h estrous response, total-AI pregnancy rate, or CL regression rate. In conclusion, treating yearling BI heifers with split treatments of PGF2alpha (given on two consecutive days) improved estrous response and pregnancy rates by increasing PGF2alpha-induced luteolysis.

Animals↗
PubMed2002

The fixation probability of a beneficial allele in a population dividing by binary fission.

We derive formulae for the fixation probability, P, of a rare benefical allele segregating in a population of fixed size which reproduces by binary fission, in terms of the selection coefficient for the beneficial allele, s. We find that an earlier result P approximately = 4s does not depend on the assumption of binary fission, but depends on an assumption about the ordering of events in the life cycle. We find that P approximately = 2s for mutations occurring during chromosome replication and P approximately = 2.8s for mutations occurring at random times between replication events.

Alleles↗
PubMed2005

Effect of inorganic versus organic selenium on hen production and egg selenium concentration.

A 28-d experiment using 288 Hy-Line W-36 laying hens was conducted to compare sodium selenite (SS) with Se-enriched yeast (SY). The Se from SS or SY was supplemented into a corn-soybean meal basal diet at 0, 0.15, 0.30, 0.60, or 3.00 ppm, and the basal diet was formulated to provide 0.82% lysine and 2,950 kcal/kg of ME. Each treatment was replicated 4 times with 2 cages of 4 hens per cage in each replicate. Hen production was assessed daily, and 2 eggs per replicate were collected every 4 d for whole-egg Se analysis. Albumen quality was assessed at 2 egg storage temperatures (7.2 vs. 22.2 degrees C) with the eggs collected on d 24 and 28, respectively. The percentage of dirty and cracked eggs was greater (P < 0.04) in hens fed SY than in those fed SS. Percentage hen-day production was not affected (P > 0.05) by diet. Albumen quality of eggs stored at 22.2 degrees C was improved (P < 0.04) in eggs from hens fed SS, but there was no difference (P > 0.05) in albumen quality of eggs stored at 7.2 degrees C. Egg weight was linearly increased (P < 0.01) by SY. Whole-egg Se levels were linearly increased (P < 0.01) as dietary Se level increased for both sources of Se, but eggs from hens fed SY had higher (P < 0.01) Se concentrations than those fed SS. The results from this experiment indicate that percentage hen-day production is not affected by Se source, and that SY increases egg Se concentrations more than SS.

Animal Feed↗
PubMed1991

Effects of epsilon aminocaproic acid on primary hemostasis.

These studies examined the effect of an oral dose of epsilon-aminocaproic acid (EACA) on primary hemostasis. Bleeding time tests (with and without the use of a blood pressure cuff) were measured before and 2 h following EACA in 56 patients with mild bleeding disorders and/or thrombocytopenia. Preliminary studies evaluated the reproducibility of these tests in 13 patients who had bleeding times (cuff) ranging from 8.0 to greater than 20 min. Their replicate bleeding time values with cuff agreed within 2.5 min and those without cuff within 3 min. Therefore, the 56 study patients were considered to have had no change in their bleeding times after EACA, if their bleeding time with cuff was +/- 2.5 min and/or their nonoccluded value was +/- 3 min of their baseline values, respectively. An isolated increase in bleeding times was observed in 6 of 56 (11%) patients. All 6 had myelodysplasia associated with long bleeding times; their nonoccluded values increased by 5-14 min. Of the 56 study patients, 54% showed a decrease in their bleeding times following EACA. The changes were evident with venostasis in 18 of 30 (60%) and without venostasis in 12 (40%) patients. These studies suggest that EACA may improve primary hemostasis in some patients with prolonged bleeding times.

Administration, Oral↗
PubMed1999

Liver transplantation and HBsAg-positive postnecrotic cirrhosis: adequate immunoprophylaxis and delta virus co-infection as the significant determinants of long-term prognosis.

BACKGROUND/AIMS: The place of liver transplantation in hepatitis B viral (HBV)-related diseases remains controversial because of the high rate of reinfection. The aim of this study was to define the determinants of long-term prognosis after transplantation. METHODS: Fifty-eight patients were transplanted during the period February 1984-September 1996. Six patients died during the early (< 3 months) posttransplant period from causes unrelated to HBV infection. All 52 long-term (> 3 months) survivors were evaluated in relation to the mode of presentation, viral replication at time of transplantation, absence of hepatocellular cancer at time of transplantation and use of adequate immunoprophylaxis (IP). Adequate immunoprophylaxis, defined as maintenance of anti-HBs levels over 100 mUI/ml, was introduced in December 1989. Intention-to-treat IP analysis compared patients transplanted before and after this date. The median follow-up was 74 months (range 4 to 131). Forty-seven patients (90%) had a minimal follow-up of 3 years. RESULTS: Five-year actuarial survival rates of 58 patients and of 52 long-term survivors were 72 +/- 6% and 80 +/- 6%, respectively. Univariate analysis showed that delta co-infection (n = 25) significantly improved survival (p < 0.001) [96 +/- 4% vs 63 +/- 10% in HBV patients (n = 27) at 5 years] as did absence of hepatocellular cancer (n = 36) (p = 0.020) [89 +/- 5% vs 61 +/- 12% in 16 non-cancer patients]. IP, however, significantly influenced 5-year survival in the HBV-patient group (n = 17) (p = 0.001) [85 +/- 10% vs 30 +/- 14% in 10 patients without IP). Multivariate analysis selected delta co-infection (p = 0.002) and IP (p = 0.01) as the significant determinants of prognosis independently influencing survival. Uni- and multivariate analyses showed that survival without reinfection was significantly influenced by IP (p = 0.002) [73 +/- 8% (n = 31) versus 33 +/- 12% in 15 non-treated patients). CONCLUSIONS: Delta virus co-infection and immunoprophylaxis are the most important prognostic factors after transplantation for postnecrotic HBsAg-positive cirrhosis. Transplantation can be proposed as a therapeutic tool only if life-long adequate adjuvant therapy can be achieved. Under this condition good results can even be obtained if there is viral replication at the time of transplantation.

Actuarial Analysis↗
PubMed2002

Movement, replication, and emigration rates of individual bacteria in a biofilm.

Single-cell behavior within a biofilm was observed over a period of several hours. The observations were converted into quantitative stochastic rules governing the behavior of individual cells within a biofilm. Such a quantitative summary provides not only a concise description of the results but also information helpful when constructing computer models of dynamic biofilm systems. The time to division, emigration, and rate of motility of individual green fluorescent protein labeled Pseudomonas aeruginosa PAO1 cells in a 3-10 microm thick biofilm containing predominantly non-GFP labeled cells were calculated based on images of individual cells collected at 15-min time intervals. The biofilms were grown in flow cells and the images captured with a confocal laser microscope. Cells destined to emigrate are more active than those that remain; the geometric means for velocities in the biofilm are 1.0 microm/h for remaining cells and 1.5 microm/h for emigrating cells. The median time to emigration was 2.0 h. During the experimental observation period, the estimated probability for emigration is 0.44, illustrating that a substantial number of bacteria leave the field of view. Cells emigrate at a median time one-third that of the median time to replication. Specifically, the median time for cells to divide was 6.9 h, and it was estimated that 10% of the cells had a time to division greater than 10 h.

Biofilms↗