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PubMed2003

When cues collide: use of stress and statistical cues to word boundaries by 7- to 9-month-old infants.

Prior research suggests that stress cues are particularly important for English-hearing infants' detection of word boundaries. It is unclear, though, how infants learn to attend to stress as a cue to word segmentation. This series of experiments was designed to explore infants' attention to conflicting cues at different ages. Experiment 1 replicated previous findings: When stress and statistical cues indicated different word boundaries, 9-month-old infants used syllable stress as a cue to segmentation while ignoring statistical cues. However, in Experiment 2, 7-month-old infants attended more to statistical cues than to stress cues. These results raise the possibility that infants use their statistical learning abilities to locate words in speech and use those words to discover the regular pattern of stress cues in English. Infants at different ages may deploy different segmentation strategies as a function of their current linguistic experience.

Attention↗
PubMed1984

Helping behavior of females: effects of stress and commonality of fate.

In a design replication of Dovidio and Morris' study, the effects of stress and commonality of fate on helping behavior were examined. Ss were randomly assigned to one of four conditions: high stress/common fate (n = 15), high stress/dissimilar fate (n = 15), or low stress/common fate (n = 15), or low stress/dissimilar fate (n = 15). While the initial study involved male Ss, the present study involved females in order to assess the generality of the original findings. Other aspects of the original experiment were repeated as closely as possible. Consistent with the original study, a significant interaction was found, indicating that Ss were more helpful under conditions of high stress and common fate. Results also revealed a greater overall amount of helping behavior than that found by Dovidio and Morris.

Adult↗
PubMed2002

Stress-induced premature senescence or stress-induced senescence-like phenotype: one in vivo reality, two possible definitions?

No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in "stress-induced premature senescence-like phenotype" according to definition 1 or "stress-induced premature senescence," according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as "telomere-dependent" replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (patho)physiology and aging.

Aging↗
PubMed2005

Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.

The availability of full genome sequences has allowed the construction of microarrays, with which screening of the full genome for changes in gene expression is possible. This method can provide a wealth of information about biology at the level of gene expression and is a powerful method to identify genes and pathways involved in various processes. In this study, we report a detailed analysis of the full heat stress response in Drosophila melanogaster females, using whole genome gene expression arrays (Affymetrix Inc, Santa Clara, CA, USA). The study focuses on up- as well as downregulation of genes from just before and at 8 time points after an application of short heat hardening (36 degrees C for 1 hour). The expression changes were followed up to 64 hours after the heat stress, using 4 biological replicates. This study describes in detail the dramatic change in gene expression over time induced by a short-term heat treatment. We found both known stress responding genes and new candidate genes, and processes to be involved in the stress response. We identified 3 main groups of stress responsive genes that were early-upregulated, early-downregulated, and late-upregulated, respectively, among 1222 differentially expressed genes in the data set. Comparisons with stress sensitive genes identified by studies of responses to other types of stress allow the discussion of heat-specific and general stress responses in Drosophila. Several unexpected features were revealed by this analysis, which suggests that novel pathways and mechanisms are involved in the responses to heat stress and to stress in general. The majority of stress responsive genes identified in this and other studies were downregulated, and the degree of overlap among downregulated genes was relatively high, whereas genes responding by upregulation to heat and other stress factors were more specific to the stress applied or to the conditions of the particular study. As an expected exception, heat shock genes were generally found to be upregulated by stress in general.

Animals↗
PubMed1997

Photoelastic analysis of miniplate osteosynthesis for mandibular angle fractures.

OBJECTIVE: The purpose of this study was to reassess Champy's findings, which were instrumental in justifying the theory of tension band plating for mandibular angle fractures. STUDY DESIGN: Ten anatomically correct mandibles were fabricated with a photoelastic resin. In five mandibles, angle fractures were created and fixed with a superior border miniplate; five uncut mandibles served as controls. Each mandible was loaded in a manner that simulated physiologic conditions. The internal stress patterns were preserved within the models by completing a stress freezing cycle. RESULTS: The stress patterns in the experimental mandibles virtually replicated the patterns seen in the controls. Stress fringes were present surrounding the outer screws, indicating that these screws were subjected to pull-out forces. CONCLUSIONS: There is greater force on the outer screws that may contribute to fixation failure. The theory of tension band plating for mandibular angle fractures is accurate but Champy's model is oversimplified.

Birefringence↗
PubMed1996

Two distinct modes of strand unlinking during theta-type DNA replication.

DNA gyrase and topoisomerase IV (Topo IV) are type II bacterial DNA topoisomerases that show a high degree of similarity to each other yet appear to have different functions during DNA replication. We show here that the torsional stress generated during theta-type DNA replication in vitro can take the form of either positive supercoils ahead of the replication fork or catenane-like right-handed windings (precatenanes) of the two partially replicated duplexes behind the fork. Gyrase prefers to act on the former, whereas Topo IV prefers the latter. Removal of either form of positive winding can support nascent chain elongation, but only precatenane removal can support the final stages of DNA replication: processing of the late intermediate and daughter chromosome decatenation.

DNA Replication↗
PubMedDate not supplied

Age-dependent response of primary human dermal fibroblasts to oxidative stress: cell survival, pro-survival kinases, and entrance into cellular senescence.

A central question in cell biology is how cells become senescent. After a finite number of cell divisions, normal cultured human cells enter a state of irreversible growth arrest, termed "replicative senescence." Alternatively, oxidative stress in the form of hydrogen peroxide (H(2)O(2)) can render human dermal fibroblasts (HDFs) nonproliferative and quiescent, a phenomenon known as stress-induced premature senescence (SIPS). Although critical to the understanding of the pathophysiological basis of many diseases, there is no research to date that has simultaneously examined the interactions between age, oxidative stress, and SIPS. Therefore, the goals of this study were to examine in concert the interactions between these three factors in primary HDFs, and to test our central hypothesis that aging lowers the ability of primary HDFs to respond to oxidative stress. Our data provide, for the first time, evidence that aging dramatically reduces the capacity of primary HDFs to respond to the challenge of hydrogen peroxide. Specifically, aged HDFs showed decreased cell viability, decreased phosphorylation (activation) of pro-survival kinases (Akt and ERK 1/2), and increased entrance into a senescent state when compared with their younger counterparts. Another important conclusion of this study is that blockade of transforming growth factor-beta1 had a pronounced "rescue effect" in the aged, preventing entrance of HDFs into cellular senescence.

Adolescent↗
PubMed2002

Cardiac mechanoenergetics in silico.

The aim of this thesis is to investigate the link between biochemical intracellular processes and mechanical contraction of the cardiac muscle. First, the regulation of intracellular energy fluxes between mitochondria and myofibrils is studied. It is shown, that the experimentally observed metabolic stability of the cardiac muscle is reproducible by a simple feedback regulation mechanism, i.e., ATP consumption in myofibrils and ATP production in mitochondria are balanced by the changes of the high energy phosphate concentrations. Second, an important property of energy transformation from biochemical form to mechanical work in the cardiac muscle, the linear relationship between the oxygen consumption and the stress-strain area, is replicated by a cross-bridge model. Third, by using the developed cross-bridge model, the correlation between ejection fraction of the left ventricle and heterogeneity of sarcomere strain, developed stress and ATP consumption in the left ventricular wall is established. Fourth, an experimentally observed linear relationship between oxygen consumption and the pressure-volume area can be predicted theoretically from a linear relationship between the oxygen consumption and the stress-strain area. Summing up, it is shown how the macrovariables of a cardiac muscle are interwoven with intracellular physiological processes into a whole.

Actomyosin↗
PubMed2006

Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase.

If cells are treated with DNA damaging agents or inhibitors that interfere with ongoing DNA replication, the intra-S and S/M checkpoints delay progression through S phase and mitotic entry, respectively, to allow time for DNA repair and replication restart. In vertebrates, these checkpoint responses to replication blocks are largely mediated by the sensor kinase ATR and its major downstream effector kinase Chk1. Increasing evidence suggests that the ATR pathway is also vital in the absence of exogenous stresses, i.e., during "unperturbed" replication. Both ATR and Chk1 are essential proteins in vertebrates, and lack of components of the ATR/Chk1 pathway can result in impaired replication and spontaneous DNA damage. Here we give an overview of how the ATR/Chk1 pathway responds to exogenously blocked replication and then describe evidence for roles of this pathway during replication in an unperturbed S phase.

Animals↗
PubMed2001

Multistage carcinogenesis in cell culture.

Rodent fibroblasts explanted from embryos to culture undergo a period of declining growth rate in serial passages leading to crisis, followed by the appearance of variants which can multiply indefinitely. If the "immortal" cell line was established by low density passage, i.e., 3T3 cells, it has a low saturation density and is non-tumorigenic. If it was established by high density passage, it has a high saturation density and is tumorigenic. The establishment of cells goes through successive stages, including increased capacity to multiply in low serum concentration, growth to high saturation density, growth in suspension, assisted tumour formation in susceptible hosts and unassisted tumour formation. Chromosome aberrations and aneuploidy occur long before the capacity to produce tumours appears. Contrary to conventional belief, human fibroblast populations also undergo a continuous loss of capacity to multiply from the time of explantation, with only the longest surviving clone reaching the Hayflick limit. Neoplastic transformation of rodent cells is strongly favoured by maintaining them in a quiescent state at confluence for prolonged periods, which results in genetic damage to the cells. It also produces a large variety of chromosomal aberrations in human cells and extends their replicative lifespan. Individual clones are more susceptible to spontaneous transformation than their heterogeneous parental cultures. The implications of these results for tumour development in vivo are that oncogenic genetic changes may be common under stressful conditions which restrict replication, and that such changes are maximized when a rogue clone reaches a critical size that reduces stabilizing interactions with neighbouring clones. An alternative explanation, described in the Addendum, which we retrospectively favor is that the easily transformed clones are a minority in the uncloned parental population. The reason they transform before the parental population is that when they are expanded, they have more transformable cells available under the selective condition of confluence than the uncloned parental population from which they are derived.

Cell Culture Techniques↗
PubMed2003

Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure: association with posttraumatic stress disorder.

BACKGROUND: Larger heart rate responses to sudden, loud (startling) tones represent one of the best-replicated psychophysiologic markers for posttraumatic stress disorder (PTSD). This abnormality may be a pretrauma vulnerability factor, ie, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD on traumatic exposure. Alternately, it may be an acquired PTSD sign, ie, it may have developed after the traumatic exposure, along with the PTSD. Studying identical twins discordant for traumatic exposure offers an opportunity to resolve these competing origins. METHODS: Subjects included pairs of Vietnam combat veterans and their non-combat-exposed, monozygotic twins. Combat veterans were diagnosed as having current PTSD (n = 50) or non-PTSD (ie, never had) (n = 53). All subjects listened to a series of 15 sudden, loud tone presentations while heart rate, skin conductance, and orbicularis oculi electromyogram responses were measured. RESULTS: Consistent with previous reports, averaged heart rate responses to the tones were larger in Vietnam combat veterans with PTSD. These larger responses were not shared by their non-combat-exposed co-twins, whose responses were similar to those of the non-PTSD combat veterans and their non-combat-exposed co-twins. This result remained significant after adjusting for a number of potentially confounding factors. CONCLUSIONS: The results suggest that larger heart rate responses to sudden, loud tones represent an acquired sign of PTSD rather than a familial vulnerability factor.

Acoustic Stimulation↗
PubMed1989

Birth stress, handedness and cognitive performance.

Information regarding conditions during pregnancy and delivery was obtained by extensive interviews with mothers to left-handed and right-handed students. Using the same criterion as van Strien, Bouma and Bakker (1987) for defining birth stress, the present study did not replicate their findings of higher frequency of reported birth stress in left-handers. The difference in outcome was ascribed to differences in recruitment of subjects, the present sample constituting a majority of left hand writers from a population of 921 students, while the van Strien sample was less well defined. The present study was extended by comparing left-handed and right-handed subjects (separated for sex) with and without birth stress, on verbal and nonverbal abilities, and on eye dominance, early learning difficulties and familial sinistrality. Left eye dominance was more frequent in male left-handers with birth stress. Birth stress alone had negative effects on cognitive performance, different for males and females.

Adult↗
PubMed1999

Studies on effective PCR screening strategies for white spot syndrome virus (WSSV) detection in Penaeus monodon brooders.

We re-tested stored (frozen) DNA samples in 5 independent polymerase chain reaction (PCR) replicates and confirmed that equivocal test results from a previous study on white spot syndrome virus (WSSV) in brooders and their offspring arose because amounts of WSSV DNA in the test samples were near the sensitivity limits of the detection method. Since spawning stress may trigger WSSV replication, we also captured a fresh batch of 45 brooders for WSSV PCR testing before and after spawning. Replicates of their spawned egg batches were also WSSV PCR tested. For these 45 brooders, WSSV prevalence before spawning was 67% (15/45 1-step PCR positive, 15/45 2-step PCR positive and 15/45 2-step PCR negative). Only 27 (60%) spawned successfully. Of the successful spawners, 56% were WSSV PCR positive before spawning and 74% after. Brooders (15) that were heavily infected (i.e. 1-step PCR positive) when captured mostly died within 1 to 4 d, but 3 (20%) did manage to spawn. All their egg batch sub-samples were 1-step PCR positive and many failed to hatch. The remaining 30 shrimp were divided into a lightly infected group (21) and a 2-step PCR negative group (9) based on replicate PCR tests. The spawning rates for these 2 groups were high (81 and 78%, respectively). None of the negative spawners (7) became WSSV positive after spawning and none gave egg samples positive for WSSV. In the lightly infected group (21), 6 brooders were 2-step WSSV PCR negative and 15 were 2-step WSSV PCR positive upon capture. However, all of them were WSSV PCR positive in replicate tests and after spawning or death. Four died without spawning. The remaining 17 spawned but only 2 gave egg samples PCR negative for WSSV. The other 15 gave PCR positive egg samples, but they could be divided into 2 spawner groups: those (7) that became heavily infected (i.e. 1-step PCR positive) after spawning and those (8) that remained lightly infected (i.e. became or remained 2-step PCR positive only). Of the brooders that became heavily infected after spawning, almost all egg sample replicates (91 %) tested 2-step PCR positive. One brooder even gave heavily infected (i.e. 1-step PCR positive) egg samples. For the brooders that remained lightly infected after spawning, only 27% of the egg sample replicates were 2-step PCR positive. Based on these results, we recommend that to avoid false negatives in WSSV PCR brooder tests screening tests should be delayed until after spawning. We also recommend, with our PCR detection system, discarding all egg batches from brooders that are 1-step PCR positive after spawning. On the other hand, it may be possible with appropriate monitoring to use eggs from 2-step PCR positive brooders for production of WSSV-free or lightly infected postlarvae. These may be used to stock shrimp ponds under low-stress rearing conditions.

Animals↗
PubMed2002

Modelling telomere shortening and the role of oxidative stress.

Extensive evidence supports the idea that progressive telomere loss contributes to the phenomenon of cell replicative senescence, but the mechanisms responsible for telomere loss are still unclear. In addition to the widely recognized end-replication problem, there is evidence that oxidative stress plays a major role in determining the rate of loss of telomeric DNA, and the action of a C-strand-specific exonuclease is also suggested to be important. We describe a mathematical model which examines the different contributions of these mechanisms to telomere loss and its role in triggering cell senescence. The model allows us to make quantitative predictions about the rates of telomere loss resulting from these alternative mechanisms, and their interactions. By varying the key parameters of the model, it is possible to examine the extent to which the different hypotheses are compatible with quantitative and qualitative features of the experimental data. For example, the model predicts that under low levels of oxidative stress, the main mechanisms of telomere shortening are the end-replication problem plus C-strand processing. However, when levels of oxidative stress are higher, as in cell cultures grown under normoxic or hyperoxic conditions, the model predicts that single strand breaks make an important contribution to telomere loss and their inclusion within the model is necessary to explain the data. We suggest that theoretical models of this kind are valuable tools to bridge the gap between the verbal statements of hypotheses and their rigorous experimental test.

Humans↗
PubMedDate not supplied

The relationship of burnout, stress, and hardiness in nurses in a military medical center: a replicated descriptive study.

The purpose of this descriptive study was to determine whether the personality trait of hardiness is a predictor of burnout and whether it can buffer the effect of stress on burnout. Forty-nine registered nurses working in 7 special care units completed the Tedium Burnout Scale, the Nursing Stress Scale, and the Hardiness Test. Results indicate that burnout, stress, and hardiness had a significant relationship (P < .001). Hierarchical multiple regression analysis indicated that hardiness alone accounted for 35% of burnout variance (P < .05) and that the addition of stress had no effect. A previous study reported that burn unit nurses had the least burnout and greatest hardiness. However, in this study, nurses from the Burn Intensive Care Unit had the highest burnout and stress scores and the lowest hardiness scores of nurses from the 7 units. This study confirms findings by a previous study that hardiness is a predictor of burnout but is not a buffer in the stress-burnout relationship. To further understand burnout and hardiness, longitudinal and multisite studies that include burn units are recommended.

Adult↗
PubMed2001

Mitochondrial transcription factor A (mtTFA) and diabetes.

Mitochondrial DNA (mtDNA) content decreased in an age-dependent manner and may be one of the causal factors in age-related type 2 diabetes. Mitochondrial transcription factor A (mtTFA), which provides the replication primer, plays a key role for the regulation of mtDNA replication and its level is proportional to mtDNA. Here, we studied on the regulatory mechanism of mtTFA expression and the factors affecting the transcriptional activity of the mtTFA promoter. The promoter of human mtTFA contains 67 CpG dinucleotides. When the plasmids bearing the mtTFA promoter (2378 bp) linked to luciferase were transiently transfected into HepG2 cells, in vitro methylation of NRF-1 site by HhaI methylase abolished the mtTFA promoter activity up to 90%, implying that the CpG methylation of NRF-1 site inactivate mtTFA promoter-driven transcriptional activity. Besides the promoter methylation, the exogenous hydrogen peroxide or glucose also modulates the promoter activity of mtTFA. The bacterially overexpressed mtTFA protein exhibits a strong binding affinity to circular DNA (perhaps to mtDNA in mitochondria in vivo) and the protection of the DNA from cleavage by a hydrogen peroxide attack. Taken all these results together, age-related alterations of oxidative stress may affect mtDNA replication via regulating mtTFA activity. Furthermore, a vicious cycle may be present between mtTFA protein level and oxidative stress in the sense of DNA damage. Further studies were necessary to prove the presence of methyl cytosine in the mtTFA promoter of either an aged or a diabetic person and the effect of oxidative stress on the mtTFA function and expression resulting in a change of the mtDNA copy number.

Amino Acid Sequence↗
PubMed2006

Role of 2-5A-dependent RNase-L in senescence and longevity.

Senescence is a permanent growth arrest that restricts the lifespan of primary cells in culture, and represents an in vitro model for aging. Senescence functions as a tumor suppressor mechanism that can be induced independent of replicative crisis by diverse stress stimuli. RNase-L mediates antiproliferative activities and functions as a tumor suppressor in prostate cancer, therefore, we examined a role for RNase-L in cellular senescence and aging. Ectopic expression of RNase-L induced a senescent morphology, a decrease in DNA synthesis, an increase in senescence-associated beta-galactosidase activity, and accelerated replicative senescence. In contrast, senescence was retarded in RNase-L-null fibroblasts compared with wild-type fibroblasts. Activation of endogenous RNase-L by 2-5A transfection induced distinct senescent and apoptotic responses in parental and Simian virus 40-transformed WI38 fibroblasts, respectively, demonstrating cell type specific differences in the antiproliferative response to RNase-L activation. Replicative senescence is a model for in vivo aging; therefore, genetic disruption of senescence effectors may impact lifespan. RNase-L-/- mice survived 31.7% (P<0.0001) longer than strain-matched RNase-L+/+ mice providing evidence for a physiological role for RNase-L in aging. These findings identify a novel role for RNase-L in senescence that may contribute to its tumor suppressive function and to the enhanced longevity of RNase-L-/- mice.

Aging↗