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At least 955 records · Page 53Linked to original sources
PubMed2000

p38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release. Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system.

In cardiac myocytes, the stimulation of p38 MAPK by the MAPKK, MKK6, activates the transcription factor, NF-kappaB, and protects cells from apoptosis. In the present study in primary neonatal rat cardiac myocytes, constitutively active MKK6, MKK6(Glu), bound to IkappaB kinase (IKK)-beta and stimulated its abilities to phosphorylate IkappaB and to activate NF-kappaB. MKK6(Glu) induced NF-kappaB-dependent interleukin (IL)-6 transcription and IL-6 release in a p38-dependent manner. IL-6 protected myocardial cells against apoptosis. Like IL-6, TNF-alpha, which activates both NF-kappaB and p38, also induced p38-dependent IL-6 expression and release and protected myocytes from apoptotis. While TNF-alpha was relatively ineffective, IL-6 activated myocardial cell STAT3 by about 8-fold, indicating a probable role for this transcription factor in IL-6-mediated protection from apoptosis. TNF-alpha-mediated IL-6 induction was inhibited by a kinase-inactive form of the MAPKKK, TGF-beta activated protein kinase (Tak1), which is known to activate p38 and NF-kappaB in other cell types. Thus, by stimulating both p38 and NF-kappaB, Tak1-activating cytokines, like TNF-alpha, can induce IL-6 expression and release. Moreover, the myocyte-derived IL-6 may then function in an autocrine and/or paracrine fashion to augment myocardial cell survival during stresses that activate p38.

Animals↗
PubMed2006

A network-based analysis of polyanion-binding proteins utilizing yeast protein arrays.

The high affinity of certain cellular polyanions for many proteins (polyanion-binding proteins (PABPs)) has been demonstrated previously. It has been hypothesized that such polyanions may be involved in protein structure stabilization, stimulation of folding through chaperone-like activity, and intra- and extracellular protein transport as well as intracellular organization. The purpose of the proteomics studies reported here was to seek evidence for the idea that the nonspecific but high affinity interactions of PABPs with polyanions have a functional role in intracellular processes. Utilizing yeast protein arrays and five biotinylated cellular polyanion probes (actin, tubulin, heparin, heparan sulfate, and DNA), we identified proteins that interact with these probes and analyzed their structural and amino acid sequence requirements as well as their predicted functions in the yeast proteome. We also provide evidence for the existence of a network-like system for PABPs and their potential roles as critical hubs in intracellular behavior. This investigation takes a first step toward achieving a better understanding of the nature of polyanion-protein interactions within cells and introduces an alternative way of thinking about intracellular organization.

Amino Acid Sequence↗
PubMed2005

Perceived stress and physiological dysregulation in older adults.

We use a population-based representative sample of older Taiwanese to investigate links between respondents' perceived levels of stress and a broad set of biological measures. These biomarkers were collected at a single time (2000) and reflect sympathetic nervous system (SNS)-activity, hypothalamo-pituitary-adrenal (HPA)-activity, immune function, cardiovascular function, and metabolic pathways. We model the relationship between perceived stress and (1) extreme values for each of 16 individual biological indicators; and (2) a measure of cumulative physiological dysregulation based on the full set of biomarkers. We consider two measures of perceived stress, one derived from the 2000 interview and the second based on data from three interviews (1996-2000). Age and sex-adjusted models reveal significant associations between measures of perceived stress and extreme values of cortisol, triglycerides, interleukin-6 (IL-6), dehydroepiandrosterone sulphate (DHEAS) and fasting glucose. Examined individually, numerous biomarkers, including those pertaining to blood pressure and obesity, are not significantly related to perceived stress. Jointly, however, the measure of cumulative physiological dysregulation is associated with both the level of perceived stress at a given time and to a longitudinal measure of perceived stress. Some results suggest that the relationship between level of perceived stress and physiological response is stronger for women than men.

Aged↗
PubMed2004

The influence of exterior dust and soil lead on interior dust lead levels in housing that had undergone lead-based paint hazard control.

To aid in understanding the contribution of exterior dust/soil lead to postintervention interior dust lead, a subset of housing from the HUD Lead-Based Paint Hazard Control Grant Program Evaluation was selected for study. Housing from 12 state and local governments was included. Exterior entry and street dust samples were obtained by a vacuum method, and soil samples were building perimeter core composites. Interior dust wipe lead data (microg/ft(2)) and paint lead data (mg/cm(2)) were also available for each of the dwelling units and included in the modeling. Results from 541 dwelling units revealed a wide range of exterior dust and soil lead levels, within and between grantees. Minimum and maximum geometric mean lead levels, by grantee, were 126 and 14400 microg/ft(2) for exterior entry dust; 325 and 4610 microg/ft(2) for street dust; and, for soil concentration, 383 and 2640 ppm. Geometric mean exterior entry dust lead concentration (1641 ppm) was almost four times as high as street dust lead concentration (431 ppm), suggesting that lead dust near housing was often a source of street dust lead. Geometric mean exterior entry dust lead loading was more than four times as high as window trough dust lead loading and more than an order of magnitude higher than interior entry dust lead loading. Statistical modeling revealed pathways from exterior entry dust lead loading to loadings on interior entryway floors, other interior floors, and windowsills. Paint lead was found to influence exterior entry dust lead. Results of this study show that housing where soil lead hazard control activities had been performed had lower postintervention exterior entry, interior entry floor, windowsills, and other floor dust loading levels. Soil was not present for almost half the buildings. Statistical analysis revealed that exterior strategy influenced soil lead concentration, and soil lead concentration influenced street dust lead loading. This study represents one of the few where an impact of soil treatments on dust lead levels within the housing has been documented and may represent the first where an impact on exterior entry dust lead has been found. The inclusion of measures to mitigate the role of exterior sources in lead hazard control programs needs consideration.

Dust↗
PubMed2006

Transcriptomics, proteomics and interactomics: unique approaches to track the insights of bioremediation.

Microbial mediated bioremediation has a great potential to effectively restore contaminated environment, but the lack of information about factors regulating the growth and metabolism of various microbial communities in polluted environment often limits its implementation. Newly seeded techniques such as transcriptomics, proteomics and interactomics offer remarkable promise as tools to address longstanding questions regarding the molecular mechanisms involved in the control of mineralization pathways. During mineralization, transcript structures and their expression have been studied using high-throughput transcriptomic techniques with microarrays. Generally however, transcripts have no ability to operate any physiological response; rather, they must be translated into proteins with significant functional impact. These proteins can be identified by proteomic techniques using powerful two-dimensional polyacrylamide gel electrophoresis (2-DE). Towards the establishment of functional proteomics, the current advances in mass spectrometry (MS) and protein microarrays play a central role in the proteomics approach. Exploring the differential expression of a wide variety of proteins and screening of the entire genome for proteins that interact with particular mineralization regulatory factors would help us to gain insights into bioremediation.

Biodegradation, Environmental↗
PubMed1998

Regulation of septum formation in Aspergillus nidulans by a DNA damage checkpoint pathway.

In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear division before the formation of the first septum. Previous characterization of temperature-sensitive sepB and sepJ mutations showed that although they block septation, they also cause moderate defects in chromosomal DNA metabolism. Results presented here demonstrate that a variety of other perturbations of chromosomal DNA metabolism also delay septum formation, suggesting that this is a general cellular response to the presence of sublethal DNA damage. Genetic evidence is provided that suggests that high levels of cyclin-dependent kinase (cdk) activity are required for septation in A. nidulans. Consistent with this notion, the inhibition of septum formation triggered by defects in chromosomal DNA metabolism depends upon Tyr-15 phosphorylation of the mitotic cdk p34nimX. Moreover, this response also requires elements of the DNA damage checkpoint pathway. A model is proposed that suggests that the DNA damage checkpoint response represents one of multiple sensory inputs that modulates p34nimX activity to control the timing of septum formation.

Aspergillus nidulans↗
PubMed2001

Core heritable personality characteristics and relapse in alcoholics.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were David S. Janowsky and Jan Fawcett. The presentations were (1) The tridimensional personality questionnaire: Predictor of relapse in detoxified alcoholics, by Kurt Meszaros; (2) Novelty seeking predicts clinical trial attrition in alcoholics, by Jan Fawcett; (3) Personality and alcohol/substance use disorder patient relapse and attendance at self-help group meetings, by David S. Janowsky; and (4) A three-pathway psychobiological model for craving for alcohol, by Roel Verheul.

Alcoholism↗
PubMed2000

Mechanisms of central pain.

Central pain is common in patients with stroke, multiple sclerosis, syringomyelia, and spinal cord injury. It frequently develops after a delay of weeks or months, is associated with sensory change involving the spinothalamic pathways, and has a poor prognosis for spontaneous remission. Hypotheses to explain the varied clinical manifestations can be divided in two categories: those stressing aberrant neural activity in the deafferented circuits and those focusing on the postlesion imbalance between facilitatory and inhibitory neural pathways. All models inherently assume a degree of specialization of cerebral structures in pain processing, which has not been proved conclusively.

Central Nervous System Diseases↗
PubMed2005

Genome-wide monocytic mRNA expression in polytrauma patients for identification of clinical outcome.

Immune activation in multiple trauma is closely linked to the development of multiple organ dysfunction and failure, and consequently, has a profound influence on patient outcome. Although peripheral blood monocytes play a critical role in this immune response, the biological significance of changes in genome-wide expression immediately after traumatic injury have not been explored previously. Thirteen patients presenting with multiple blunt trauma were studied. Peripheral blood monocytes were obtained within 90 min and at 6, 12, 24, 48, and 72 h after trauma. Apparent genome-wide expression was determined with Affymetrix U133A microarrays. Supervised analysis identified 698 probe sets that were differentially expressed in the 13 trauma subjects (P < 0.001) over the 72-h study period. An additional 763 probe sets were differentially expressed in patients who died (n = 3) compared with those who survived (n = 10). The ability of these probe sets to function as a classifier of survival was significantly demonstrated with six prediction models. Using pathway analysis, a network of proinflammatory genes and intracellular signaling pathways leading to c-JUN activation were consistently overexpressed in patients who died. Genome-wide mRNA expression patterns in circulating peripheral blood monocytes from multiple-injured patients can discriminate clinical outcome. The pattern of gene expression in patients who died suggests that in these individuals, there is a reprioritization of gene expression consistent with an early activation of selected genes involved in the initiation and propagation of a proinflammatory response.

Adult↗
PubMed2001

Dissecting the superoxide dismutase-ascorbate-glutathione-pathway in chloroplasts by metabolic modeling. Computer simulations as a step towards flux analysis.

The present study introduces metabolic modeling as a new tool to analyze the network of redox reactions composing the superoxide dismutase-ascorbate (Asc)-glutathione (GSH) cycle. Based on previously determined concentrations of antioxidants and defense enzymes in chloroplasts, kinetic properties of antioxidative enzymes, and nonenzymatic rate constants of antioxidants with reactive oxygen, models were constructed to simulate oxidative stress and calculate changes in concentrations and fluxes of oxidants and antioxidants. Simulated oxidative stress in chloroplasts did not result in a significant accumulation of O2*- and H2O2 when the supply with reductant was sufficient. Model results suggest that the coupling between Asc- and GSH-related redox systems was weak because monodehydroascorbate radical reductase prevented dehydroascorbate (DHA) formation efficiently. DHA reductase activity was dispensable. Glutathione reductase was mainly required for the recycling of GSH oxidized in nonenzymatic reactions. In the absence of monodehydroascorbate radical reductase and DHA reductase, glutathione reductase and GSH were capable to maintain the Asc pool more than 99% reduced. This suggests that measured DHA/Asc ratios do not reflect a redox balance related to the Asc-GSH-cycle. Decreases in Asc peroxidase resulted in marked H2O2 accumulation without significant effects on the redox balance of Asc/DHA or GSH/GSSG. Simulated loss of SOD resulted in higher H2O2 production rates, thereby affecting all subsequent steps of the Asc-GSH-cycle. In conclusion, modeling approaches contribute to the theoretical understanding of the functioning of antioxidant systems by pointing out questions that need to be validated and provide additional information that is useful to develop breeding strategies for higher stress resistance in plants.

Ascorbic Acid↗
PubMed1995

Characterization of TAP-independent and brefeldin A-resistant presentation of Sendai virus antigen to CD8+ cytotoxic T lymphocytes.

H-2Kb-transfected T2 cells, which lack both TAP1/2 and LMP2/7 genes, are able to efficiently process and present Sendai virus Antigen to Kb-restricted Sendai virus-specific CTL. This presentation is not inhibited by Brefeldin A (BFA). Here we extend our analysis of this novel antigen presentation pathway. We show that presentation of Sendai virus antigen was not due to sensitization of T2Kb cells by peptides in the virus preparation or peptides released from virus infected cells. Also, the ability to present Sendai virus in a BFA resistant fashion was specific for cells of the T2 lineage. Re-expression of TAP1/2 genes in T2Kb cells did not alter the capability to present antigen in a BFA resistant fashion, i.e. the presence of a functional TAP transporter complex did not relocate (all) peptides to the classical pathway for antigen processing and presentation. We found that co-infection of T2Kb cells with either Sendai virus plus influenza virus or Sendai virus plus VSV did not relocate presentation of influenza or VSV antigen to the TAP independent BFA resistant antigen presentation pathway. Peptide elution experiments and studies with peptide-specific CTL firmly demonstrated that the antigen presented by T2Kb cells after infection with Sendai virus was the natural Sendai virus epitope NP324-332. The same epitope, when expressed as a minigene in vaccinia virus, could be presented also by T2Kb cells but this presentation could be blocked by BFA. Thus, the TAP independent BFA resistant presentation of antigen seem cell (T2 lineage) and virus (Sendai virus) specific, but not epitope specific. The ability of T2Kb cells to present Sendai virus antigen in a TAP independent BFA resistant fashion was only partially blocked by lysosomal inhibitors such as methylamine, ammonium chloride and chloroquine. These findings demonstrate that TAP1/2-independent and BFA-resistant class I processing is only expressed in certain cell types, in parallel with classical MHC class I processing, and that Sendai virus selectively can enter this pathway. Hypothetical models for the TAP-independent class I processing are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

The Auburn Elective Surgery Pilot Project.

BACKGROUND: The aim of this project was to increase rates of day surgery, reduce elective surgical waiting lists, give patients a guaranteed date of surgery and improve operating theatre utilization. The guiding principle behind the project was to treat the administration of elective surgery as a separate business unit, distinct from emergency surgery. METHODS: Elective surgical referrals for admission from throughout the Western Sydney Health Area Service were pooled. The procedure for surgical admissions was altered in three areas: (i) the use of a new booking and waiting list system administered by a dedicated nurse coordinator who generated the lists for surgery; (ii) restructuring the elective surgical operating sessions; and (iii) planning post-discharge care at the time of operation using model clinical pathways. RESULTS AND CONCLUSIONS: During the project period, the number of the selected surgical procedures performed doubled. Fifty-seven per cent of patients were discharged on the day of surgery. Surgeons took less time to perform procedures. By the end of the trial period, waiting lists for the selected procedures were eliminated. Operating costs as evaluated by the Centre for Health Economics Research and Evaluation were reduced by 25%. The administrative changes to surgical admissions resulted in improved cost and patient throughput for elective surgical admissions with no adverse patient outcomes.

Ambulatory Surgical Procedures↗
PubMed2005

Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia.

Identification of the neural basis of the visual deficits experienced by humans with amblyopia, particularly when associated with strabismus (strabismic amblyopia), has proved to be difficult in part because of the inability to observe directly the neural changes at various levels of the human visual pathway. Much of our knowledge has necessarily been obtained on the basis of sophisticated psychophysical studies as well as from electrophysiological explorations on the visual pathways in animal models of amblyopia. This study combines these two approaches to the problem by employing similar psychophysical probes of performance on animal models of two forms of amblyopia (deprivation and strabismic) to those employed earlier on human amblyopes (Hess & Field, 1994, Vis. Res., 34, 13397-13406). The tests explore two competing explanations for the visual deficits, namely an evenly distributed loss of neural connections (undersampling) with the amblyopic eye as opposed to disordered connections with this eye (neural disarray). Unexpectedly, the results in animal models of deprivation amblyopia were not in accord with expectations based upon an even distribution of lost connections with the amblyopic eye. However, the results were similar to those observed in a strabismic amblyopic animal and to strabismic amblyopic humans. We suggest that deprivation amblyopia may be accompanied by an uneven loss of connections that results in effective neural disarray. By contrast, amblyopia associated with strabismus might arise from neural disarray of a different origin such as an alteration of intrinsic cortical connections.

Amblyopia↗
PubMed2006

Genetic and environmental influences on Person x Situation profiles.

Genetic and environmental influences on Person x Situation interactions were studied using data of the German Observational Study of Adult Twins. The performance of 168 monozygotic and 132 dizygotic twin pairs in 15 tasks was observed by 120 judges who never met the twins in person. Four judges observed one twin of each pair in one task. Twin similarities in Person x Situation profiles were analyzed via (a) correlations across tasks between co-twins' Person x Situation profiles (their personality signatures) and (b) common-pathway genetic models that partitioned genetic and environmental contributions to trait levels and to Person x Situation interactions. Genes accounted for about 25% of the reliable Person x Situation interactions, whereas shared environmental influences were negligible.

Adolescent↗
PubMed2006

Structure and function of the 3-carboxy-cis,cis-muconate lactonizing enzyme from the protocatechuate degradative pathway of Agrobacterium radiobacter S2.

3-carboxy-cis,cis-muconate lactonizing enzymes participate in the protocatechuate branch of the 3-oxoadipate pathway of various aerobic bacteria. The gene encoding a 3-carboxy-cis,cis-muconate lactonizing enzyme (pcaB1S2) was cloned from a gene cluster involved in protocatechuate degradation by Agrobacterium radiobacter strain S2. This gene encoded for a 3-carboxy-cis,cis-muconate lactonizing enzyme of 353 amino acids - significantly smaller than all previously studied 3-carboxy-cis,cis-muconate lactonizing enzymes. This enzyme, ArCMLE1, was produced in Escherichia coli and shown to convert not only 3-carboxy-cis,cis-muconate but also 3-sulfomuconate. ArCMLE1 was purified as a His-tagged enzyme variant, and the basic catalytic constants for the conversion of 3-carboxy-cis,cis-muconate and 3-sulfomuconate were determined. In contrast, Agrobacterium tumefaciens 3-carboxy-cis,cis-muconate lactonizing enzyme 1 could not, despite 87% sequence identity to ArCMLE1, use 3-sulfomuconate as substrate. The crystal structure of ArCMLE1 was determined at 2.2 A resolution. Consistent with the sequence, it showed that the C-terminal domain, present in all other members of the fumarase II family, is missing in ArCMLE1. Nonetheless, both the tertiary and quaternary structures, and the structure of the active site, are similar to those of Pseudomonas putida 3-carboxy-cis,cis-muconate lactonizing enzyme. One principal difference is that ArCMLE1 contains an Arg, as opposed to a Trp, in the active site. This indicates that activation of the carboxylic nucleophile by a hydrophobic environment is not required for lactonization, unlike earlier proposals [Yang J, Wang Y, Woolridge EM, Arora V, Petsko GA, Kozarich JW & Ringe D (2004) Biochemistry43, 10424-10434]. We identified citrate and isocitrate as noncompetitive inhibitors of ArCMLE1, and found a potential binding pocket for them on the enzyme outside the active site.

Agrobacterium tumefaciens↗
PubMedDate not supplied

Peer rejection and neglect of latency-age children: pathways and a group psychotherapy model.

TOPIC: Children's peer relations are one of the most powerful predictors of mental health PROBLEMS: Peer rejection and neglect are associated with depression, academic problems, school withdrawal, and delinquency. PURPOSE: To provide brief introductions to models of social development and peer rejection, and to introduce a developmental-group psychotherapy model for children experiencing peer neglect or rejection. SOURCES: Theoretical and empirical literature, as well as clinical experience. CONCLUSIONS: Early identification and intervention with children vulnerable to peer rejection are essential. Research addressing affective experiences of peer-rejected children and the relationships between self-perception and treatment outcomes is needed.

Child↗
PubMed2000

Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease.

Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid beta-peptides (A beta). Thus, lowering A beta production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as beta-, gamma-, and alpha-secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic alpha-secretase pathway in model systems. Talsaclidine was administered double-blind, placebo-controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total A beta were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of A beta significantly over time within the treatment group (n = 20) by a median of 16% as well as compared to placebo (n = 4) by a median of 27%. We conclude that treatment with selective M1 agonists may reduce A beta production and may thus be further evaluated as a potential amyloid-lowering therapy of AD.

Aged↗