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PubMed2001

Large-scale chromatin fibers of living cells display a discontinuous functional organization.

We investigated the chromatin organization of living cells with a combination of recently developed approaches for histone and DNA labeling. Nucleosomal DNA was labeled with a histone H2B-GFP (green fluorescent protein) fusion protein and the chromatin organization of living HeLa cells was analyzed by high resolution confocal microscopy. Within the perinuclear and perinucleolar regions chromatin was organized into large-scale fibers of 2 to 8 microm in length and 300 to 500 nm in diameter. Within the nuclear interior we observed similar large-scale fibers, but in addition focal as well as diffuse forms of organization. Comparison with standard labeling and detection procedures revealed major differences in the chromatin organization observed. Chromatin organization revealed by the distribution of histone H2B-GFP was directly compared with the functional organization of chromatin by Cy3-dUTP labeling of DNA replicating at a specific time. DNA regions replicating at a specific time display characteristic physical and functional properties. Analysis of Cy3-labeled foci revealed that they are associated with all three forms of chromatin organization (fibrillar, focal and diffuse). In particular, Cy3-labeled foci appeared as discontinuous regions of large-scale fibers. These results demonstrate that large-scale chromatin fibers have discontinuous functional characteristics.

Carbocyanines↗
PubMed1988

Reproducibility of intra-abdominal pressure when lifting.

Reproducibility of intra-abdominal pressure (IAP) variation was investigated in fifteen young male subjects when lifting three loads, 49, 98 and 147 N, with three speeds of movement, slow, fast and spontaneous, and starting from four standing postures: trunk erect, trunk forward flexed at 30, 60, and 90 degrees of dorsolumbar inclination. Each lift was replicated five times successively and the whole protocol was replicated at one a week interval. The intra-individual variability in IAP response was assessed using the standard deviation of each series of ten lifts. Results showed that variability of peak IAP increased with the load and with the lifting speed. This effect of speed was especially observed for light loads and in forward bending postures. Trunk posture had in itself no significant effect on IAP reproducibility. However, when the variations in the moment acting at lumbar level were taken into account by considering the IAP to moment ratio, the reproducibility of the response was not affected by the load but only by the trunk posture. Reproducibility was lower in the erect posture than in the three flexed positions. It is suggested that this difference relates to the importance in each posture of the moment acting at the shoulder with respect to the total moment acting at lumbar level.

Abdomen↗
PubMed1999

The timing between skeletal muscle myoblast replication and fusion into myotubes, and the stability of regenerated dystrophic myofibres: an autoradiographic study in mdx mice.

In mdx mice, a model for Duchenne muscular dystrophy, the timing between the replication of myoblasts and their incorporation into myotubes was determined autoradiographically. Thirty-eight mdx mice aged 23 d were injected with tritiated thymidine to label myoblasts replicating early in the dystrophic process. At intervals from 8 h to 30 d after injection the tibialis anterior muscles were removed, processed for autoradiography and analysed for labelled central myonuclei (derived from the progeny of myoblasts which had been labelled at 23 d). At 8 h after injection there were no labelled central myonuclei, showing that the labelled myoblasts had not fused within this time. At 1 d, 2 % of central myonuclei were labelled, at 2 d, up to 32% were labelled, at 3 d approximately 60% were labelled, and at 4 d the labelling peaked at 74%. In the 27 mice sampled from 5-30 d after injection, the levels of central myonuclear labelling varied enormously: from 1-63%. However, there was a consistent decrease in the numbers of labelled central myonuclei with time. This may have been due to dilution of the relative numbers of labelled myonuclei due to other, nonlabelled, myoblasts replicating after the availability of tritiated thymidine, and fusing. It was also possible that labelled myofibres underwent subsequent necrosis and were eliminated from the muscle. The proposal that a regenerated myofibre can undergo a subsequent cycle of necrosis and regeneration was supported by evidence of some necrotic myofibres with labelled and unlabelled central nuclei. These results have implications for understanding the cellular biology and pathology of dystrophic muscle, particularly in relation to myoblast transfer therapy as a potential treatment of Duchenne muscular dystrophy.

Animals↗
PubMed1996

Caregiver burden in partners of Vietnam War veterans with posttraumatic stress disorder.

Caregiver burden in 58 partners of Vietnam veterans with posttraumatic stress disorder (PTSD) was examined. The relationship between patient PTSD severity and caregiver burden, as well as the effect of several caregiver and patient variables on caregiver psychological status, was evaluated twice, an average of 8 months apart. Patient symptom severity was positively correlated with caregiver burden. Time 1 cross-sectional analysis indicated that greater caregiver burden was associated with greater caregiver psychological distress, dysphoria, and anxiety. Patient symptom severity also contributed to caregiver psychological distress; financial stress contributed to caregiver dysphoria and trait anxiety. Time 2 cross-sectional analyses essentially replicated the Time 1 findings. A third set of analyses examining change scores indicated that changes in caregiver burden for individuals in the sample positively predicted individual changes in caregiver psychological distress, dysphoria, and state anxiety.

Adult↗
PubMed1993

The structure of replicating kinetoplast DNA networks.

Kinetoplast DNA (kDNA), the mitochondrial DNA of Crithidia fasciculata and related trypanosomatids, is a network containing approximately 5,000 covalently closed minicircles which are topologically interlocked. kDNA synthesis involves release of covalently closed minicircles from the network, and, after replication of the free minicircles, reattachment of the nicked or gapped progeny minicircles to the network periphery. We have investigated this process by electron microscopy of networks at different stages of replication. The distribution of nicked and closed minicircles is easily detectable either by autoradiography of networks radiolabeled at endogenous nicks by nick translation or by twisting the covalently closed minicircles with intercalating dye. The location of newly synthesized minicircles within the network is determined by autoradiography of network is determined by autoradiography of networks labeled in vivo with a pulse of [3H]thymidine. These studies have clarified structural changes in the network during replication, the timing of repair of nicked minicircles after replication, and the mechanism of division of the network.

Animals↗
PubMed2006

DomainSieve: a protein domain-based screen that led to the identification of dam-associated genes with potential link to DNA maintenance.

MOTIVATION: The Dam methyltransferase (DamMT) activity, broadly distributed in association with restriction endonucleases, as part of the restriction-modification defense systems, has evolved to become intimately associated with essential biological functions in a few organisms. In Escherichia coli, DamMT is involved in multiple aspects of DNA maintenance, replication initiation, daughter chromosome segregation, DNA mismatch repair, gene expression control, etc. The participation of DamMT in such a diverse set of functions required that other genes adapted, or emerged through evolution, in response to the DamMT-induced modification of the genomic environment. One example is SeqA, a protein that senses the methylation status of the origin of replication of the chromosome to control the timing of replication initiation. Interestingly, seqA is only present in a few DamMT-specifying proteobacteria. This observation led us to hypothesize that other genes, specifying related functions, might also be found in these organisms. To test this hypothesis, we implemented a large-scale comparative genomic screen meant to identify genes specifying DNA methylation sensing domains, probably involved in DNA maintenance functions. RESULTS: We carried out a phylogenetic analysis of DamMT, identifying two contrasting behaviors of the protein. Based on this phylogeny, we defined precisely a set of genomes, in which the protein activity is likely to be involved in DNA maintenance functions, the 'resident' dam genomes. We defined a second set of genomes, in which DamMT is not resident. We developped a new tool, 'DomainSieve', in order to screen these two sets for protein domains that are strictly associated with 'resident' dam genomes. This approach was rewarding and generated a list of genes, among which some, at least, specify activities with clear linkage to DamMT-dependent DNA methylation and DNA maintenance. AVAILABILITY: DomainSieve is implemented as a web resource and is accessible at http://stat.genopole.cnrs.fr/ds/.

Algorithms↗
PubMed2000

Efficacy of neomycin sulfate water medication on the control of mortality associated with colibacillosis in growing turkeys.

The objective of this investigation was to evaluate the efficacy, safety, and toxicity of neomycin sulfate (Neomix 325) water medication to control mortality associated with colibacillosis (Escherichia coli) in growing turkeys. One efficacy trial was conducted at five locations; each location included 2,880 sexed 21-d-old turkey poults that were naturally challenged with litter from turkey flocks that had colibacillosis. Between 5 and 7 d after challenge, and when mortality had reached 0.5%, poults were randomized within sex into three treatment groups of 0, 11, or 22 mg neomycin sulfate/kg body weight. In each location, each treatment was replicated 12 times with 40 poults per sex per replicate. All treatments were administered in the drinking water for 5 d. The pivotal decision criterion was mortality. Mortality was defined as 1) supported mortality (SM): positive microbial culture for E. coli and gross lesions, 2) diagnosed mortality (DM): diagnosed as associated with E. coli but not supported by lesions or positive microbiological cultures, 3) overall mortality (OM): mortality associated with E. coli or other microorganisms and miscellaneous reasons such as accidents (trampling or suffocations). Performance data (growth and feed utilization) also were measured and are reported without statistical analysis. Results from this efficacy study clearly demonstrated the effectiveness of neomycin sulfate against E. coli as measured by a reduction in mortality. In the target animal safety and toxicity study (done in conjunction with the efficacy study), neomycin sulfate in the drinking water at 66, 110, or 220 mg/kg per d for 15 d had no observable adverse effects on poult performance, as measured by feed or water consumption, body weight, gross pathology, or mortality.

Animal Nutritional Physiological Phenomena↗
PubMed1991

The chromatin structure of Saccharomyces cerevisiae autonomously replicating sequences changes during the cell division cycle.

The chromatin structures of two well-characterized autonomously replicating sequence (ARS) elements were examined at their chromosomal sites during the cell division cycle in Saccharomyces cerevisiae. The H4 ARS is located near one of the duplicate nonallelic histone H4 genes, while ARS1 is present near the TRP1 gene. Cells blocked in G1 either by alpha-factor arrest or by nitrogen starvation had two DNase I-hypersensitive sites of about equal intensity in the ARS element. This pattern of DNase I-hypersensitive sites was altered in synchronous cultures allowed to proceed into S phase. In addition to a general increase in DNase I sensitivity around the core consensus sequence, the DNase I-hypersensitive site closest to the core consensus became more nuclease sensitive than the distal site. This change in chromatin structure was restricted to the ARS region and depended on replication since cdc7 cells blocked near the time of replication initiation did not undergo the transition. Subsequent release of arrested cdc7 cells restored entry into S phase and was accompanied by the characteristic change in ARS chromatin structure.

Cell Cycle↗
PubMed2005

Genome-wide gene expression in response to parasitoid attack in Drosophila.

BACKGROUND: Parasitoids are insect parasites whose larvae develop in the bodies of other insects. The main immune defense against parasitoids is encapsulation of the foreign body by blood cells, which subsequently often melanize. The capsule sequesters and kills the parasite. The molecular processes involved are still poorly understood, especially compared with insect humoral immunity. RESULTS: We explored the transcriptional response to parasitoid attack in Drosophila larvae at nine time points following parasitism, hybridizing five biologic replicates per time point to whole-genome microarrays for both parasitized and control larvae. We found significantly different expression profiles for 159 probe sets (representing genes), and we classified them into 16 clusters based on patterns of co-expression. A series of functional annotations were nonrandomly associated with different clusters, including several involving immunity and related functions. We also identified nonrandom associations of transcription factor binding sites for three main regulators of innate immune responses (GATA/srp-like, NF-kappaB/Rel-like and Stat), as well as a novel putative binding site for an unknown transcription factor. The appearance or absence of candidate genes previously associated with insect immunity in our differentially expressed gene set was surveyed. CONCLUSION: Most genes that exhibited altered expression following parasitoid attack differed from those induced during antimicrobial immune responses, and had not previously been associated with defense. Applying bioinformatic techniques contributed toward a description of the encapsulation response as an integrated system, identifying putative regulators of co-expressed and functionally related genes. Genome-wide studies such as ours are a powerful first approach to investigating novel genes involved in invertebrate immunity.

Animals↗
PubMed2003

The dihydrofolate reductase origin of replication does not contain any nonredundant genetic elements required for origin activity.

The Chinese hamster dihydrofolate reductase (DHFR) origin of replication consists of a broad zone of potential initiation sites scattered throughout a 55-kb intergenic spacer, with at least three sites being preferred (ori-beta, ori-beta', and ori-gamma). We previously showed that deletion of the most active site or region (ori-beta) has no demonstrable effect on initiation in the remainder of the intergenic spacer nor on the time of replication of the DHFR locus as a whole. In the present study, we have now deleted ori-beta', both ori-beta and ori-beta', an 11-kb region just downstream from the DHFR gene, or the central approximately 40-kb core of the spacer. The latter two deletions together encompass >95% of the initiation sites that are normally used in this locus. Two-dimensional gel analysis shows that initiation still occurs in the early S phase in the remainder of the intergenic spacer in each of these deletion variants. Even removal of the 40-kb core fails to elicit a significant effect on the time of replication of the DHFR locus in the S period; indeed, in the truncated spacer that remains, the efficiency of initiation actually appears to increase relative to the corresponding region in the wild-type locus. Thus, if replicators control the positions of nascent strand start sites in this complex origin, either (i) there must be a very large number of redundant elements in the spacer, each of which regulates initiation only in its immediate environment, or (ii) they must lie outside the central core in which the vast majority of nascent strand starts occur.

Animals↗
PubMed1993

Transcription of ftsZ oscillates during the cell cycle of Escherichia coli.

The FtsZ protein is a key element controlling cell division in Escherichia coli. A powerful transcription titration assay was used to quantify the ftsZ mRNA present in synchronously dividing cells. The ftsZ mRNA levels oscillate during the cell cycle reaching a maximum at about the time DNA replication initiates. This cell cycle dependency is specifically due to the two proximal ftsZ promoters. A strain was constructed in which expression of ftsZ could be modulated by an exogenous inducer. In this strain cell size and cell division frequency were sensitive to the cellular FtsZ contents, demonstrating the rate-limiting role of this protein in cell division. Transcriptional activity of the ftsZ promoters was found to be independent of DnaA, indicating that DNA replication and cell division may be independently controlled at the time when new rounds of DNA replication are initiated. This suggests a parallelism between the prokaryotic cell cycle signals and the START point of eukaryotic cell cycles.

Bacterial Proteins↗
PubMed1978

Genetic mapping of the chromosome of Rhizobium trifolii.

Cultures of the wild strain and auxotrophic mutants of Rhizobium trifolii T37 synchronized by means of phenylethanol have been mutagenized with nitrosoguanidine. Fifteen genetic markers were characterized in respect of their order and the time of replication based on the peaks of mutations of the genes. The time of R. trifolii chromosome replication was estimated using inhibitors of the initiation of DNA replication: rifampicin, chloramphenicol and phenylethanol. The replicative map of R. trifolii chromosome has been constructed. Taking into account the replicative map, linkages of the genes, and the bidirectional model of the Rhizobium chromosome replication, a circular genetic map of the chromosome of R. trifolii T37 was elaborated.

Chloramphenicol↗
PubMed1980

Analysis of life-shortening effects in female BALB/C mice fed 2-acetylaminofluorene.

A total of 4320 female BALB/cStCrlfC3H/Nctr mice were continuously fed 2-acetylaminofluorene (2-AAF) in the diet at various concentrations in order to obtain a quantitative assessment of dose-related life-shortening effects. Statistical procedures which adjust for extraneous deaths were used to analyze the survival data. In addition to the demonstration of a reduced survival time associated with bladder and liver tumors induced by 2-AAF, a further toxic effect was observed at 150 ppm. Since the experiment was replicated six times, variability in the survival times of animals in different replicates was studied. Although all replicates were conducted under specific pathogen free / defined flora (SPF/DF) conditions, a significant change in survival time was demonstrated across replicates.

2-Acetylaminofluorene↗
PubMed1998

Improving power with repeated measures: diet and serum lipids.

The inability to detect associations between diet and serum cholesterol in cross-sectional population studies has been attributed to measurement error in diet assessments and between-subject variability in lipid concentrations. Current statistical methods can reduce the effects of measurement error and allow within-subject comparisons when replicate measures on individuals are available, even if the time between replicates is as long as 4 y and replicate data are not available for all subjects. Data from 928 nondiabetic participants of the San Luis Valley Diabetes Study with measures of 24-h dietary intake and fasting lipid concentrations at baseline, at a 4-y follow-up visit, or both were analyzed in a random-effects model that allowed for an unbalanced design. Sex was included as a non-time-varying covariate and age, body mass index, and energy intake were included as time-varying covariates. The findings when LDL cholesterol (mmol/L) was regressed on saturated fat intake (20 g/d) with all observations in a random-effects model (beta = 0.14, P = 0.0016) were compared with results with observations restricted to the first visit only (beta = 0.05, P = 0.52), a balanced design using averages across visits (beta = -0.12, P = 0.28), and a balanced design with random effects obtained by excluding subjects without two observations (beta = 0.12, P = 0.0092). Study power was greatest in the random-effects model using all observations and time-varying covariates. These findings highlight the importance of even a single replicate observation on a subsample of subjects. We recommend analyzing all data rather than averaging measures across visits or omitting observations to create a balanced design.

Adult↗
PubMed1988

[A model of localized iconic memory, replicable and associative, using time sharing and 3 neuronal communication modes].

A model is proposed for the functioning of an iconic memory involving several layers of neurones. A small group of neurones in one layer project their terminations over the terminations of a single neurone of the superior layer. According to the communication mode (emission or reception), a neurone in one layer can memorize the state of the terminations of a neurone of the superior layer, or impose on the latter the state of its own terminations. In the comparison mode, an emitting neurone compares its state to another emitting neurone and, in case of sufficient similarity, switches to the reception mode (associative recall). The first layer, corresponding to short-term memory, communicates with the cells involved in the representation of the perceived image. This model makes possible the establishment of a correspondence between a percept and a neurone, the replication of memorized configurations, the restructuration of memory and, starting with a percept or a memorized item, the integral associative recall of all similar memorized items.

Humans↗
PubMed1983

Cell cycle time and possible early DNA replication in C-band regions in the domestic pig (Sus scrofa) lymphocytes.

Dynamic cell replication studies on peripheric blood lymphocytes cultured from the domestic pig (Sus scrofa) were performed. Replication started after 18-24 hr in culture and the cell cycle time was about 8-10 hr. Chromosomes from cells at first division showed C-banded-like regions. This finding suggests the occurrence of early DNA replication zones within the constitutive heterochromatin of the pig chromosomes.

Animals↗
PubMed2004

Children's mental health in times of economic recession: replication and extension of the family economic stress model in Finland.

This study evaluated the applicability of the family economic stress model (FESM) in understanding the influences of economic hardship on child mental health during a nationwide economic recession in Finland. The information was gathered from 527 triads of 12-year-olds and their mothers and fathers from a population sample. The structural equation models showed that the FESM fit the data well, indicating its generalizability in Finnish society. The results confirmed that a reduction in disposable family income constitutes a risk for child mental health through increased economic pressure and negative changes in parental mental health, marital interaction, and parenting quality. Controlling the children's prerecession mental health substantiated that economic hardship can lead to deterioration in children's mental health. Alternative models based on fully recursive analyses revealed reciprocal influences between parents and their children over time: Children's prerecession mental health problems predicted compromised parenting, which in turn contributed to children's internalizing and externalizing symptoms during the recession.

Adult↗