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PubMed2004

Bacteroid proline catabolism affects N(2) fixation rate of drought-stressed soybeans.

In prior work, we observed that soybean (Glycine max L. cv Merr.) seeds inoculated with a mutant Bradyrhizobium japonicum strain unable to catabolize Pro (Pro dehydrogenase(-) [ProDH(-)]) resulted in plants that, when forced to depend on N(2) fixation as the sole source of nitrogen and subjected to mild drought stress, suffered twice as large a loss in seed yield as did plants inoculated with the parental strain. Here, we used a continuous gas flow system to measure H(2) evolution as a function of time and leaf water potential (Psi(L)). Since one H(2) is produced for every N(2) fixed as an obligate part of the mechanism of N(2) fixation, these measurements serve as the basis for continuous monitoring of the N(2) fixation rate. In five replicate experiments, the slope of the decline in N(2) fixation rate in response to water stress was always greater for plants inoculated with the mutant strain unable to catabolize Pro or take up H(2) (ProDH(-), hup(-)) than it was for plants inoculated with the parental strain (ProDH(+), hup(-)). In aggregate, the probability that this difference occurred by chance alone was 0.005. In combination with the earlier result, this is consistent with bacteroid catabolism of Pro synthesized in response to mild drought stress having a positive impact on N(2) fixation rate and seed yield.

Bradyrhizobium↗
PubMed2003

The interacting pathways for prevention and repair of oxidative DNA damage.

Genomes are damaged by spontaneous decay, chemicals, radiation and replication errors. DNA damage may cause mutations resulting in inheritable disease, cancer and ageing. Oxidative stress from ionising radiation and oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by reactive oxygen species (ROS) generated, e.g. O2(.-) (superoxide radical), OH. (hydroxyl radical) and H2O2 (hydrogen peroxide). ROS also oxidise RNA, lipids, proteins and nucleotides. The first line of defence against ROS is enzymatic inactivation of superoxide by superoxide dismutase and inactivation of the less toxic hydrogen peroxide by catalase. As a second line of defence, incorporation of damaged bases into DNA is prevented by enzymes that hydrolyse oxidised dNTPs (e.g. 8-oxodGTP) to the corresponding dNMP. The third line of defence is repair of oxidative damage in DNA by an intricate network of DNA repair mechanisms. Base excision repair (BER), transcription-coupled repair (TCR), global genome repair (GGR), mismatch repair (MMR), translesion synthesis (TLS), homologous recombination (HR) and non-homologous end-joining (NHEJ) all contribute to repair of oxidative DNA damage. These mechanisms are also integrated with other cellular processes such as cell cycle regulation, transcription and replication and even use some common proteins. BER is the major pathway for repair of oxidative base damage, with TCR and MMR being important backup pathways for repair of transcribed strands and newly replicated strands, respectively. In recent years, several new DNA glycosylases that initiate BER of oxidative damage have been identified. These have specificities overlapping with previously known DNA glycosylases and serve as backups, and may have distinct roles as well. Thus, there is both inter- and intra-pathway complementation in repair of oxidative base damage, explaining the limited effects of absence of single DNA glycosylases in animal model systems.

Base Pair Mismatch↗
PubMed2000

Depression and social stress in Pakistan.

BACKGROUND: The high prevalence of depression in developing countries is not well understood. This study aimed to replicate the previous finding of a high prevalence of depression in Pakistan and assess in detail the associated social difficulties. METHOD: A two-phase survey of a general population sample in a Pakistani village was performed. The first-phase screen used the Personal Health Questionnaire (PHQ) and the self-rating questionnaire (SRQ). A one in two sample of high scorers and a one in three sample of the low scorers were interviewed using the Psychiatric Assessment Schedule (PAS) and Life Events and Difficulties Schedule (LEDS). RESULTS: A total of 259 people were screened (96% response rate). The second stage yielded 55 cases, of whom 54 had depressive disorder, and 48 non-cases. The adjusted prevalence of depressive disorders was 44-4% (95% CI 35.3 to 53.6): 25.5% in males and 57.5% in females. Nearly all cases had lasted longer than 1 year. Comparison of the cases and non-cases indicated that cases were less well educated, had more children and experienced more marked, independent chronic difficulties. Multivariate analysis indicated that severe financial and housing difficulties, large number of children and low educational level were particularly closely associated with depression. CONCLUSION: This study confirms the high prevalence of depressive disorders in Pakistan and suggests that this may be higher than other developing countries because of the high proportion of the population who experience social adversity.

Adult↗
PubMed2002

Neuroimaging findings in post-traumatic stress disorder. Systematic review.

BACKGROUND: Findings from neuroimaging studies complement our understanding of the wide-ranging neurobiological changes in trauma survivors who develop post-traumatic stress disorder (PTSD). AIMS: To determine whether neuroimaging studies had identified structural and functional changes specific to PTSD. METHOD: A review of all functional and structural neuroimaging studies of subjects with PTSD was carried out. Studies were identified using general medical and specific traumatic stress databases and paper searches of current contents and other secondary sources. RESULTS: The most replicated structural finding is hippocampal volume reduction, which may limit the proper evaluation and categorisation of experience. Replicated localised functional changes include increased activation of the amygdala after symptom provocation (which may reflect its role in emotional memory) and decreased activity of Broca's area at the same time (which may explain the difficulty patients have in labelling their experiences). CONCLUSIONS: Evidence from neuroimaging studies has suggested areas of the brain that may be damaged by psychological trauma. The clinical implications of these neuroimaging findings need to be investigated further because they challenge traditional therapeutic approaches.

Amygdala↗
PubMed2001

From inequity to burnout: the role of job stress.

This research examined burnout (i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment) among 2 samples of Dutch teachers as a function of inequity and experienced job stress in 3 different exchange relationships (with students, colleagues, and the school). It was hypothesized that inequity would be linked to burnout through the stress resulting from this inequity. Analysis of a cross-sectional sample (N = 271) revealed that this was indeed the case. Findings were replicated longitudinally using an independent sample of 940 teachers. It is concluded that the often-reported effect of inequity on burnout can partly be interpreted in terms of elevated levels of job stress. Implications of the findings are discussed.

Achievement↗
PubMed1996

Direct isolation of longevity mutants in the nematode Caenorhabditis elegans.

We have isolated several new EMS-induced, long-lived mutants of Caenorhabditis elegans, using a novel screen that eliminates the need for replica plating. Three new alleles of age-1 (z10, z12, and z25) were identified by failure to complement age-1 (hx546) for life span extension; these alleles had life spans ranging from 18.9 to 25.9 days at 25 degrees C, with an average 46% increase in life span. After backcrossing, alleles were examined in a wild-type background for resistance to several environmental stresses: heat (35 degrees C), ultraviolet (UV) light (20 J/m2), and hydrogen peroxide (H2O2) (0.5 M). Two replicates of the test of thermotolerance were completed on each strain, giving mean survivals of 842 min (hx546), 810 min (z10), 862 min (z12), and 860 min (z25), compared to 562 min for wild type. All the age-1 alleles were significantly tolerant, compared with wild type (P < 0.001). Two replicates for UV resistance were also completed with mean survivals of 103, 118, 108, and 89 hr, respectively, compared to 72 hr for wild type. One test of hydrogen peroxide resistance has shown that z12 and N2 had a mean survival of 41 hr, while the other age-1 alleles had mean survival of 54 hr (z10), and 62 hr (z25); H2O2 resistance is the only environmental stress that differentiates among the age-1 alleles.

Animals↗
PubMed2001

Assessing coping flexibility in real-life and laboratory settings: a multimethod approach.

This research sought to formulate a theoretically based conceptualization of coping flexibility and to adopt a multimethod approach in assessing this construct. A self-report daily measure and an experiment were designed geared to theoretical and empirical grounds. The new daily measure was used in Study 1 to examine coping flexibility in a life transition. Findings showed individual differences in patterns of coping flexibility across different real-life stressful events. In Study 2, coping flexibility was examined in both real-life and laboratory settings. Results replicated those of Study 1 and further revealed consistency between the self-report and the experiment data. Study 3 extended previous studies by adopting a longitudinal design over a 3-month time span. Participants' flexibility in coping with laboratory tasks was found to predict how flexible they would be in handling real-life stressful events.

Adaptation, Psychological↗
PubMed1976

Chloroplast Growth and Replication in Germinating Spinach Cotyledons following Massive gamma-Irradiation of the Seed.

Spinach seeds (Spinacia oleracea L.) given massive doses of gamma-irradiation (500 krad) germinate and form a seedling with two green cotyledons and a radicle, but develop no further. Irradiated cotyledons show no increase in cell number or total DNA over a 7-day period in the light, while in control cotyledons there is a small increase in cell number and large increases in total DNA and chloroplast number. The chloroplasts of irradiated cotyledons are delayed in their division, become greatly enlarged and contain large amounts of starch. The whole population of chloroplasts subsequently undergoes a wave of division. The daughter chloroplasts show normal thylakoid development, but have some abnormal structural features caused by the radiation stress. Information on the effect of X-irradiation, ultraviolet irradiation, and 5-fluorodeoxyuridine on chloroplast replication and on chloroplast and nuclear DNA synthesis was obtained from cultured spinach leaf discs. It appears that chloroplast replication is more resistant to ionizing radiation than cell division and can proceed in the absence of nuclear DNA synthesis and greatly reduced chloroplast DNA synthesis.

Journal Article↗
PubMed2003

Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication.

Legionella pneumophila can replicate inside amoebae and also alveolar macrophages to cause Legionnaires' Disease in susceptible hosts. When nutrients become limiting, a stringent-like response coordinates the differentiation of L. pneumophila to a transmissive form, a process mediated by the two-component system LetA/S and the sigma factors RpoS and FliA. Here we demonstrate that the broadly conserved RNA binding protein CsrA is a global repressor of L. pneumophila transmission phenotypes and an essential activator of intracellular replication. By analysing csrA expression and the phenotypes of csrA single and double mutants and a strain that expresses csrA constitutively, we demonstrate that, during replication in broth, CsrA represses every post-exponential phase phenotype examined, including cell shape shortening, motility, pigmentation, stress resistance, sodium sensitivity, cytotoxicity and efficient macrophage infection. At the transition to the post-exponential phase, LetA/S relieves CsrA repression to induce transmission phenotypes by both FliA-dependent and -independent pathways. For L. pneumophila to avoid lysosomal degradation in macrophages, CsrA repression must be relieved by LetA/S before phagocytosis; conversely, before intracellular bacteria can replicate, CsrA repression must be restored. The reciprocal regulation of replication and transmission exemplified by CsrA likely enhances the fitness of microbes faced with fluctuating environments.

Animals↗
PubMed1991

Stress and sodium hypertension in baboons: neuroendocrine and pharmacotherapeutic assessments.

Behavioral stress and high dietary salt have been reported to increase blood pressure additively in non-human primates. This study was designed to replicate this phenomenon and to assess neuroendocrine correlates and responses to two commonly used antihypertensives, a beta-adrenoceptor blocker and a thiazide diuretic. High-salt intake (240 mmol sodium per day) and stress were administered for 9 weeks in adult baboons. Oral atenolol hydrochloride (50 mg, twice daily) or hydrochlorothiazide (25 mg/day) was administered for 2 weeks each. In all four baboons, salt loading and stress increased systolic blood pressure (SBP) chronically by 14 mmHg, with increases in water intake, urine osmolality and excretion of sodium, decreases in levels of serum sodium, plasma renin activity and plasma vasopressin and no changes in urinary excretion of norepinephrine or epinephrine. Neither drug decreased SBP during ongoing high salt and stress. The results confirm the additive chronic effects of high-dietary salt intake and behavioral stress on blood pressure in non-human primates. The hypertension in this model is resistant to two antihypertensive drugs commonly used clinically.

Animals↗
PubMed2003

Stressful life events in pregnancy and head circumference at birth.

A strong association between stress in pregnancy and small head circumference in infants at birth was reported in 1994. This important finding has never been replicated. In a follow-up study of 4211 participants with singleton pregnancies, information on life events was collected twice during pregnancy and head circumference measured shortly after birth following standard procedures. No association was found between experienced or perceived stress as a result of life events during pregnancy and head circumference in the infants. In conclusion, stress in pregnancy may influence foetal brain development in many ways, but we found no support for an effect on the size of the brain as measured by head circumference at birth.

Birth Weight↗
PubMed1985

Stress and health among Polynesian migrants to New Zealand.

A survey study of 228 Samoans, 212 Cook Islanders, and 224 native-born New Zealanders of European background randomly selected from the same working-class neighborhoods of Auckland was interviewed in their own language by same-sex interviewers on their adaptation to life in New Zealand's major industrial city. Strong positive associations were found between the number of symptoms of poor health reported and both the frequency of external situational stressors and the strength of Type A psychological attributes, which together account for 25% of the variance in health status. These statistical relationships were replicated within all ethnic and both sex groups. Social support systems, however, did not provide the stress-buffering effects anticipated, raising the issue of the possible psychic costs of maintaining these kinship ties, particularly among Samoan migrants.

Acculturation↗
PubMed2006

Monoubiquitination of proliferating cell nuclear antigen induced by stalled replication requires uncoupling of DNA polymerase and mini-chromosome maintenance helicase activities.

Proliferating cell nuclear antigen (PCNA) is a homotrimeric, ring-shaped protein complex that functions as a processivity factor for DNA polymerases. Following genotoxic stress, PCNA is modified at a conserved site by either a single ubiquitin moiety or a polyubiquitin chain. These modifications are required to coordinate DNA damage tolerance processes with ongoing replication. The molecular mechanisms responsible for inducing PCNA ubiquitination are not well understood. Using Xenopus egg extracts, we show that ultraviolet radiation and aphidicolin treatment induce the mono- and diubiquitination of PCNA. PCNA ubiquitination is replication-dependent and coincides with activation of the ataxia telangiectasia mutated and Rad3-related (ATR)-dependent DNA damage checkpoint pathway. However, loss of ATR signaling by depletion of the ATR-interacting protein (ATRIP) or Rad1, a component of the 911 checkpoint clamp, does not impair PCNA ubiquitination. Primed single-stranded DNA generated by uncoupling of mini-chromosome maintenance helicase and DNA polymerase activities has been shown previously to be necessary for ATR activation. Here we show that PCNA ubiquitination also requires uncoupling of helicase and polymerase activities. We further demonstrate that replicating single-stranded DNA, which mimics the structure produced upon uncoupling, is sufficient to induce PCNA monoubiquitination. Our results suggest that PCNA ubiquitination and ATR activation are two independent events that occur in response to a common single-stranded DNA intermediate generated by functional uncoupling of mini-chromosome maintenance (MCM) helicase and DNA polymerase activities.

Animals↗
PubMed2004

Stress response inhibits the nephrotoxicity of cisplatin.

Salt loading and saline hydration are used to protect patients from cisplatin-induced nephrotoxicity. The mechanism by which salt exerts its protective effect is unknown. As part of an ongoing study of cisplatin nephrotoxicity, an in vitro assay system was developed that models the in vivo exposure and response of proximal tubule cells to cisplatin. In this study, it was discovered that the toxicity of cisplatin toward LLC-PK(1) cells varied dramatically according to the tissue culture media used for 3-h cisplatin exposure. Further experiments revealed that minor variations in the sodium concentration among standard tissue culture media modulated cisplatin nephrotoxicity. NaCl has been shown to protect against cisplatin-induced nephrotoxicity in vivo but has never before been demonstrated in vitro. NaCl did not alter the cellular accumulation of cisplatin. NaCl altered the osmolarity of the external media, and its effect was replicated by substituting equiosmolar concentrations of impermeant anions or cations. The change in osmolarity triggered a stress response within the cell that modulated sensitivity to cisplatin. These data resolve several long-standing controversies regarding the mechanism by which salt loading protects the kidney from cisplatin-induced nephrotoxicity.

Animals↗
PubMed2000

Temporal loss of Nef-epitope CTL recognition following macaque lipopeptide immunization and SIV challenge.

To address the subtle interactions between antiviral cytotoxic T-cell (CTL) immune responses and the evolution of viral quasispecies variants in vivo, we performed a longitudinal study in a simian immunodeficiency virus (SIV)-infected rhesus macaque that had a long experimental SIV infection before developing simian AIDS. Before being infected with SIV, this animal was immunized with a mixture of seven lipopeptides derived from SIV Nef and Gag proteins and showed a bispecific antiviral CTL response directed toward Nef 169-178 and 211-225 peptides. After SIV infection, CTL activity against the Nef 169-178 epitope was no longer detectable, as assessed from peripheral blood mononuclear cells stimulated by autologous SIV. CTL activity against the 211-225 epitope was lost after 3 months, and an additional CTL response to the amino acids 112-119 Nef epitope emerged. Analysis of the Nef proviral sequence revealed the presence of immune escape variants first in the 211-225 epitope and much later in the 112-119 epitope. In contrast, epitope 169-178 showed only two mutations among all viral sequencing performed. We conclude that in this macaque, bispecific CTL exerted a strong selective pressure and escape virus mutants finally emerged. We identified CTL recognizing a conserved Nef epitope 112-119 (SYKLAIDM), essential for viral replication, which could be associated with a prolonged AIDS-free period. These results stress the importance of the induction of broader multispecific CTLs directed against highly conserved and functional T-cell epitopes by vaccination, with the aim of keeping HIV infection in check.

Amino Acid Sequence↗
PubMed1981

Acidification and sodium entry in frog skin epithelium.

Acidification of the external medium by isolated frog skin epithelium (Rana catesbeiana, Rana temporaria, and Caudiververa caudiververa) and its relationship to Na+ uptake was studied. Acidification was measured by the pH-stat technique under short-circuit or open-circuit conditions. The results of this study demonstrate that (a) acidification by these species of in vitro frog skins is not directly coupled to Na+ or anion transport; (b) acidification can be inhibited by the diuretic drug amiloride, but only at high external Na+ concentrations; (c) acidification rate in these species of frog skin is controlled in part by the metabolic production of CO2; and (d) the positive correlation between net Na+ absorption and net acidification observed in whole animal studies could not be replicated in the in vitro skin preparation, even when the frogs were first chronically stressed by salt depletion, a physiological state comparable to that used in the in vivo experiments.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Mathematical principles of cell division.

The report given here is an attempt of the mathematical formulations to solve a problem concerning cell division and the control of mass and volume of the nucleus and cytoplasm. The study of the interaction forces on the nucleus and the vibrational frequencies during cell division are analyzed in detail. Lastly, the vibrations of a cell and the coalescence of the vacuoles inside a living plant cell are discussed theoretically.

Animals↗
PubMed1995

Development and validation of a gradient reversed-phase high-performance liquid chromatographic assay for S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923) from a transdermal delivery system.

A gradient reversed-phase HPLC method for potency determination of N-0923 (10 mg) from a transdermal delivery system (TDS), was developed and validated with single point calibration using internal standard quantitation. N-0923 and the internal standard, N-0434, are eluted from a reversed-phase C18 column using a gradient which contains 0.1 M triethylamine-0.04 M citrate buffer, pH 5.9, water, and acetonitrile with UV detection at 272 nm. N-0923 is isolated from the transdermal delivery system by extraction with n-heptane followed by extraction of the resulting organic phase with 0.1 M citric acid containing the internal standard. The method was free from matrix interferences in both untreated and forced degraded placebo delivery systems. Acceptable linearity and quantitative recovery from spiked placebo delivery systems over the range 50-150% of nominal label claim were demonstrated. Within-day assay precision from individual samples of active transdermal delivery systems (n = 10) was 5.6% R.S.D. The detection limit was at least 0.1 microgram/ml which is equivalent to 0.05% of the working standard concentration. Replicate injection precision at this level was 0.08% R.S.D. (n = 4). Analysis of thermally stressed active and placebo delivery systems with this HPLC method and photodiode-array detection showed that the chromatography was stability-indicating as demonstrated by the absence of measurable interferences from principal degradation products of either the n-0923 or the delivery system excipients.

Administration, Cutaneous↗