SEARCH · Search PubMed

Results for “Interplay”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources

PubMed2002

Distinctive gene profiles occur at key points during natural metamorphosis in the Xenopus laevis tadpole tail.

Thyroid hormones (THs) are essential for tadpole metamorphosis into a juvenile frog; however, a complex interplay between additional hormones and signaling events also contributes to this dramatic developmental phase. A major mechanism of TH action is the nuclear receptor-mediated regulation of gene transcription of responsive genes. By using the precocious metamorphic model, several genes have been identified as TH responsive in the regressing tail. Many of these genes also exhibit altered expression during natural metamorphosis. Although identification of these genes provides insight into the mechanism whereby TH acts, complex interplay between TH and other hormones and the developmental stage-dependency of tissue responses contribute to the timing and coordination of metamorphic events. We investigated the temporal gene expression profile in Xenopus laevis tadpole tails from premetamorphosis through metamorphic climax by using a combination of a novel frog cDNA array containing 420 genes and quantitative real-time PCR. Seventy-nine genes were identified whose steady-state mRNA expression levels were altered in the tadpole tail during natural metamorphosis, of which 34 have previously been identified to be TH responsive in frogs or mammals. Of these genes, 75 clustered into 13 groups that displayed distinct developmental expression profiles. The levels of 28 transcripts were altered during premetamorphosis, 31 during prometamorphosis, and 43 with the onset of tail regression. This work establishes an important baseline for determining the mechanisms whereby tissues undergo differing metamorphic fates.

Animals↗

PubMed2003

Triggering of Toll-like receptors modulates IFN-gamma signaling: involvement of serine 727 STAT1 phosphorylation and suppressors of cytokine signaling.

Microbial stimuli activate cells of the innate immune system by triggering Toll-like receptors (TLR). Activation of macrophages and dendritic cells is further enhanced by secondary signals like IFN-gamma. Here we analyzed the interplay of IFN-gamma and TLR signaling in cells of the innate immune system. Using a STAT1-dependent reporter construct we show that IFN-gamma signaling can be enhanced as well as inhibited by simultaneous stimulation with either defined TLR agonists or whole-bacterial lysates. Short costimulation resulted in the amplification of IFN-gamma signaling and was attributable to the p38 mitogen-activated protein kinase (MAPK)-dependent phosphorylation of signal transducer and activator of transcription (STAT)1 on serine 727. In contrast, prolonged co-incubation as well as pre-incubation with TLR agonists led to an inhibition of IFN-gamma signaling. TLR triggering induced expression of suppressor of cytokine signaling (SOCS)-1, SOCS-3 and cytokine-inducible SH2 domain-containing protein (CIS). Overexpression of SOCS-1 and, to a lesser extend, of SOCS-3 and CIS inhibited IFN-gamma signaling as measured by activation of STAT1. Moreover, pre-incubation with TLR-dependent stimuli impaired IFN-gamma-induced MHC class II regulation but enhanced CD40 and CD86 expression. Taken together, the results indicate a tight interplay between TLR and IFN-gamma signaling pathways which involve induction of SOCS proteins and serine phosphorylation of STAT1.

Antigens, CD↗

PubMed2001

CYP3A4, CYP3A5, and MDR1 in human small and large intestinal cell lines suitable for drug transport studies.

The aim of this study was to find a cell culture model of the intestinal epithelium for use in studies of CYP3A4-mediated first-pass metabolism of drugs and also for studies of the interplay between CYP3A4 metabolism and P-glycoprotein efflux. For this purpose, the expression of CYP3A4, CYP3A5, and MDR1 mRNA was studied in three cell lines of the normal human intestinal epithelium and three transformed cell lines of colonic (Caco-2) origin. Surprisingly, only transformed cell lines were induced by 1alpha,25-dihydroxy vitamin D3 (D3) to express high amounts of CYP3A4. In contrast to the original findings for this model, the monolayer integrity was maintained during D3 treatment. Levels of CYP3A mRNA expression in Caco-2 and TC7 cells differed dramatically. The highest levels of CYP3A4 and lowest levels of CYP3A5 mRNA expression were observed in D3 treated Caco-2 cells of high passage numbers, resulting in a CYP3A4/3A5 expression ratio greater than fourfold higher than that seen in TC7 cells. Functional studies, using the CYP3A probe testosterone, showed that CYP3A activity was completely absent only in uninduced Caco-2 cells. After D3 induction, high levels of the metabolite were produced in both cell lines (149.4 +/- 12.3 and 86.5 +/- 3.8 pmol 6beta-OH testosterone/min/mg cellular protein from 75 microM testosterone in Caco-2 and TC7 cells, respectively). The maximum velocity (Vmax) and the apparent Michaelis constant (Km) for the 6beta-hydroxylation of testosterone by CYP3A4 in intact Caco-2 monolayers were similar to those obtained from human intestinal microsomes. Only minor changes in P-glycoprotein activity were observed when the metabolically stable P-glycoprotein substrate celiprolol was used. In conclusion, these results show that the features of the generally available Caco-2 cell line from American Type Culture Collection make it suitable for studies of CYP3A4-mediated first-pass metabolism and also for studies of the interplay between CYP3A4 and drug efflux mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Heat, safety or solitude? Using habitat selection experiments to identify a lizard's priorities.

Laboratory experiments with a rock-dwelling nocturnal gecko, Oedura lesueurii, showed that retreat-site selection (and other behaviours) are affected by the interplay between thermal benefits, social advantages and avoidance of predators. Velvet geckos were highly selective in habitat choice: they preferred artificial retreat-sites that mimic the thermal properties of natural rocks in full sun rather than those that mimic rocks in full shade; mature male geckos rarely shared retreat-sites with other adult males; and these lizards strongly avoided retreat-sites covered with the scent of a natural predator (the broadheaded snake, Hoplocephalus bungaroides). After documenting these preferences, we carried out additional trials in which two or more of these factors co-occurred, as is often the case in nature. Social dominance interacted with thermal benefits in determining retreat-site selection, with smaller (subordinate) males forced to use cooler retreat-sites when larger (dominant) males were present. Avoidance of predators was a higher priority than thermoregulation: the lizards would forego a warmer retreat-site with predator scent in favour of a cooler, unscented one. There was also an interplay between social dominance and predator scent: smaller males were forced to use either predator-scented retreat-sites or no retreat-site when larger males were present. General activity levels, and the frequencies of specific behavioural acts, also shifted in response to social and predator-scent cues. Our study emphasizes the complexity of habitat-selection behaviour in these lizards, and clarifies the criteria used in retreat-site selection when (as is commonly the case) the animal must choose between conflicting priorities. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMedDate not supplied

What makes a man similar to a tie? Stimulus compatibility with comparison and integration.

We argue and show that different properties of stimuli are compatible with different types of processing. Specifically, object pairs from the same taxonomic category (e.g., chair-bed) tend to be alignable and thus compatible with comparison, whereas object pairs that play different roles in thematic relations (e.g., chair-carpenter) tend to be nonalignable and compatible with integration. Using object pairs that varied orthogonally in alignability and thematic relatedness, we demonstrated that stimulus compatibility modulates processing and affects the outcomes of tasks that are currently believed to involve only comparison (similarity ratings, Experiment 1; listing commonalities and differences, Experiment 2) or only integration (thematic relatedness ratings, Experiment 3). Our findings and others that we have reviewed suggest that: (1) many cognitive tasks involve both comparison and integration, and (2) the relative influence of each process is modulated by an interplay between the task-appropriate and the stimulus-compatible process. We believe that single-process models should be extended to take this interplay into account.

Humans↗

PubMed2002

Effects of domain knowledge, working memory capacity, and age on cognitive performance: an investigation of the knowledge-is-power hypothesis.

Domain knowledge facilitates performance in many cognitive tasks. However, very little is known about the interplay between domain knowledge and factors that are believed to reflect general, and relatively stable, characteristics of the individual. The primary goal of this study was to investigate the interplay between domain knowledge and one such factor: working memory capacity. Adults from wide ranges of working memory capacity, age, and knowledge about the game of baseball listened to, and then answered questions about, simulated radio broadcasts of baseball games. There was a strong facilitative effect of preexisting knowledge of baseball on memory performance, particularly for information judged to be directly relevant to the baseball games. However, there was a positive effect of working memory capacity on memory performance as well, and there was no indication that domain knowledge attenuated this effect. That is, working memory capacity contributed to memory performance even at high levels of domain knowledge. Similarly, there was no evidence that domain knowledge attenuated age-related differences (favoring young adults) in memory performance. We discuss implications of the results for understanding proficiency in cognitive domains from an individual-differences perspective.

Adolescent↗

PubMed1998

Insulin-like growth factor I induction of c-myc expression in bovine fibroblasts can be blocked by antecedent insulin receptor activation.

We previously reported that preexposure of cultured bovine fibroblasts to insulin at low concentrations inhibits subsequent insulin-like growth factor I (IGF-I)-stimulated DNA synthesis. This insulin-induced desensitization to IGF-I is mediated by specific insulin receptors on bovine fibroblasts and occurs distally to IGF-I receptor engagement and activation. In the present study, we use this model system to determine insulin and IGF-I receptor interplay in the regulation of proto-oncogenes involved in mitogenesis. Insulin (10 nM), IGF-I (10 nM), and 10% fetal bovine serum were each capable of stimulating rapid and transient c-fos and c-myc mRNA expression in bovine fibroblasts. Expression of c-myc was most responsive to mitogenic stimuli; IGF-I and serum had equivalent potency resulting in approximately 14-fold increases in c-myc mRNA expression, while insulin produced 3- to 5-fold increases. Max mRNA, which encodes the partner protein for Myc, was constitutively expressed and levels did not change with treatment or with time. When bovine fibroblasts were pretreated with 10 nM insulin for 48 h, washed, and then stimulated with 10 nM IGF-I, alterations in c-fos mRNA expression were moderate. In contrast, insulin pretreatment completely blocked IGF-I induction of c-myc expression. This block was averted if a specific inhibitor of intracellular signaling through the phosphatidylinositol 3-kinase pathway was present during the incubation period with insulin. These data indicate significant insulin/IGF-I receptor interplay in normal bovine fibroblasts and suggest that insulin receptor-initiated signaling can profoundly alter proto-oncogene expression induced by growth factors sharing components of a common intracellular signaling network.

Animals↗

PubMed1997

Conduction block and chaotic dynamics in an asymmetrical model of coupled cardiac cells.

The initiation and propagation of the cardiac impulse depends on intrinsic properties of cells, geometrical arrangements, and intercellular coupling resistances. To address the issue of the interplay between these factors in a simple way, we have used a system, based on the van Capelle and Dürrer model, including a pacemaker and a non-pacemaker cell linked by an ohmic coupling resistance. The influence of asymmetrical cell sizes and electronic load was investigated by using numerical simulations and continuation-bifurcation techniques. The loading of a small pacemaker cell by a large non-pacemaker one (pacemaker: non-pacemaker size ratio = 0.3) was expressed as a pronounced early repolarization in the pacemaker cell and a quite long latency for the impulse propagation. Using coupling resistance as the continuation parameter, three behavioral zones were detected from low to high coupling resistance values: a zone of total quiescence (0:0), a zone of effective entertainment (1:1), and a zone of total block (1:0 pattern). At the boundary between 1:1 and 1:0 patterns, for relatively high coupling resistance values, a cascade of period doubling bifurcations emerged, corresponding to discrete changes of propagation patterns leading into irregular dynamics. Another route to irregular dynamics was also observed in the parameter space. The high sensitivity of the detected irregular dynamics to initial conditions and the positive value of the maximum Lyapunov exponent allowed us to identify these dynamics as being chaotic. Since neither intermediate block patterns nor irregular dynamics were observed with larger size ratios, we suggest that the interplay between resting membrane conductance of the non-pacemaker cell and intercellular coupling may bring about these rhythmic disturbances.

Animals↗

PubMed1995

ADH evolution and the phylogenetic footprint.

The evolution of any given protein reflects the interplay between proximal selective forces involving the conservation of protein structure and function and more general populational factors that shape the action and efficiency of natural selection. In an attempt to address that interplay, we have analyzed patterns of amino acid replacement within a well-conserved molecule, alcohol dehydrogenase (ADH), in the Drosophilidae. A sliding window, moved along the protein sequence in order to quantify the extent of change at each amino acid position, reveals heterogeneous amounts of replacement across the molecule when all ADH sequences are analyzed simultaneously. Surprisingly, the replacement profile for ADH differs significantly in the melanogaster, mulleri, and Hawaiian subgroups, reflecting the imprint of the differing evolutionary histories of each of these assemblages on the evolution of this conservative molecule.

Alcohol Dehydrogenase↗

PubMed1987

The interaction of stressful life events and chronic strains on community mental health.

One of the possible adaptive costs of coping with stress is diminished capacity to respond to subsequent adaptive demands. This paper examined the complex interplay between major life events and one source of chronic strain. Residents of the greater Los Angeles metropolitan area exposed to higher levels of smog, who had also experienced a recent stressful life event, exhibited poorer mental health than those exposed to pollution who had not experienced a recent stressful life event. There were, however, no direct effects of smog levels on mental health. These patterns of results were replicated in both a cross-sectional and a longitudinal study. The interplay of psychosocial vulnerability and environmental conditions is discussed.

Adaptation, Psychological↗

PubMed1995

Increased intracellular cyclic AMP levels suppress the mitogenic responses of human astrocytoma cells to growth factors.

It has been shown that the intracellular cAMP levels were decreased in human malignant astrocytomas. On the other hand, various growth factors and their receptors were found to be overexpressed in these tumors. It is therefore intriguing as to whether there is interplay between the two phenomena in the modulation of the astrocytoma cell growth. In a basal medium consisting of 75% DMEM, 25% Ham's F-12 supplemented with 2% FBS, we show that the mitogenic effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on human astrocytoma cells were suppressed by dibutyryl-cAMP. Dibutyryl-cAMP alone neither potentiated nor inhibited the tumor cell growth. Further studies show that PDGF-induced receptor autophosphorylation in human astrocytoma cells is suppressed by increased intracellular cAMP levels as measured by immunoprecipitation with anti-PDGF receptor and antiphosphotyrosine antibodies. Our results indicate that there is antagonistic interplay between the receptor tyrosine kinase pathway and cAMP-dependent protein kinase pathway in the control of the malignantly transformed glial cells. A reduced cAMP level seen in many human astrocytoma cells may favor their response to growth factor mitogenesis.

Astrocytoma↗

PubMed1989

Studies of the dose-effect relation.

Dose-effect relations and, specifically, cell survival curves are surveyed with emphasis on the interplay of the random factors--biological variability, stochastic reaction of the cell, and the statistics of energy deposition--that co-determine their shape. The global parameters mean inactivation dose, D, and coefficient of variance, V, represent this interplay better than conventional parameters. Mechanisms such as lesion interaction, misrepair, repair overload, or repair depletion have been invoked to explain sigmoid dose dependencies, but these notions are partly synonymous and are largely undistinguishable on the basis of observed dose dependencies. All dose dependencies reflect, to varying degree, the microdosimetric fluctuations of energy deposition, and these have certain implications, e.g. the linearity of the dose dependence at small doses, that apply regardless of unresolved molecular mechanisms of cellular radiation action.

Animals↗

PubMed1993

Medical treatment of esophageal motility disorders.

Swallowing is a complex mechanism that is based on the coordinated interplay of tongue, pharynx, and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain, or regurgitation. The major esophageal motility disorders include achalasia, diffuse esophageal spasm, hypercontractile esophagus ("nutcracker esophagus"), and hypocontractile esophagus ("scleroderma esophagus"). Other esophageal diseases such as hypopharyngeal (Zenker's) diverticula or gastroesophageal reflux disease also may be sequelae of primary esophageal motility disorder. Finally, a substantial group of patients referred for evaluation of possible esophageal motor disorders have milder degrees of dysmotility--referred to as nonspecific esophageal motor disorder--that are of unclear clinical significance. Medical treatment of esophageal motility disorders involves the uses of agents that either reduce (anti-cholinergic agents, nitrates, calcium antagonists) or enhance (prokinetic agents) esophageal contractility. Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment is often disappointing. From clinical and epidemiological studies there is some evidence for a "psychological" component in the pathogenesis or perception of esophageal symptoms. Further understanding of esophageal pathophysiology, as well as development of new receptor selective drugs, might increase our chances of successful treatment of esophageal motility disorders.

Esophageal Motility Disorders↗

PubMed2001

Neurotrophin signalling pathways regulating neuronal apoptosis.

Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival.

Animals↗

PubMed2002

[Pain and the immune system: friend or foe?].

When tissue is destroyed, pain arises. Tissue destruction as well as wound healing are associated with an inflammatory reaction. This leads to activation of nociceptors ("pain receptors") which can cross-communicate with the inflammatory infiltrate. The following review will concentrate on pain-exaggerating (hyperalgesic) and pain-ameliorating (analgesic) mediators which arise from immune cells or the circulation during the inflammation. In the early stages of inflammation endogenous hyperalgesic mediators are produced, including the proinflammatory cytokines IL-1, IL-6 and TNF-alpha, nerve growth factor as well as bradykinin and prostaglandins. Simultaneously, analgesic mechanisms are activated. Opioid peptides such as endorphins, enkephalins and dynorphins are produced by immune cells and can be released locally in the inflamed tissue on stimulation with IL-1 or corticotropin releasing factor. Analgesia is elicited by binding of the opioid peptides to receptors on peripheral sensory neurons. During the course of an inflammatory process, peripheral opioid-mediated analgesia increases. In parallel, antiinflammatory cytokines such as IL-4, IL-10, IL-13 and IL-1ra are produced and reduce hyperalgesic effects of the proinflammatory cytokines initially produced. Inflammatory pain, therefore, is the result of an interplay between hyperalgesic and analgesic mediators. Drugs such as immunosuppressants influencing this interplay may also impair endogenous hyperalgesic and analgesic mechanisms.

Humans↗

PubMed2003

Role of the microenvironment in immune responses to transplantation.

Through the constant interplay of cellular and extracellular components, the microenvironment of tissues directs immune responses. In solid organ transplantation, one factor that significantly alters the microenvironment of tissues is reperfusion injury, which occurs to a certain extent in essentially all cadaver organs. The damage that results from reperfusion injury initiates a cascade of signals to surveillance cells such as macrophages, mast cells, and dendritic cells, augmenting both innate and allo-immune responses. Chemokines, released from surveillance cells and others, orchestrate an influx of cells into the allograft, and subsequently drive the migration of dendritic cells and lymphocytes to proper areas within lymph nodes for the efficient generation of allo-immune responses. Heparan sulfate, a component of the extracellular matrix, binds chemokines and thus regulates their localization within tissues. This association is one of a multitude of examples of the interplay between cells and their extracellular surroundings. In addition to the association with chemokines, heparan sulfate binds cytokines such as IFN-gamma and IL-2. In the spleen, heparan sulfate localizes IL-2 to the marginal zone, red pulp, and interdigitating dendritic cells of the T cell zone. Our laboratory recently determined that the contribution of heparan sulfate-bound IL-2 to immune responses is substantial, finding that bound, rather than free, IL-2 drives immune responses. This finding reiterates the critical nature of the interaction between cells and the extracellular matrix. Disruptions in these interactions may lead to dysregulation of immune responses and, in turn, pathologies such as tissue fibrosis or autoimmunity. Further studies into the exchange between cells and the extracellular matrix will likely lead to new lines of therapies aimed at correcting these abnormalities before irreversible damage occurs.

Animals↗

PubMed2000

Obesity: molecular bases of a multifactorial problem.

Obesity could well become the most common health problem of the 21st century. There are more opportunities to consume large quantities of food: big portions of tasty, varied food, at reasonable prices, are available everywhere. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, since for thousands of years our species evolved in circumstances where nutrients were in short supply. The response of each individual to diet and other environmental factors varies considerably, depending on the characteristics of his/her body weight control mechanisms. The differentiating element in the future, especially as regards the dietary and pharmacological control of obesity, will be knowledge of an individual's possible response depending on his/her genetic background. Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a)feeding control, which determines the sensations of satiety and hunger through processes that depend on an interplay between internal signals (notably leptin) and environmental factors; b) energy efficiency, in particular the activation of thermogenesis mediated by uncoupling proteins (UCPs) that makes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by which cells specialised in fat storage (adipocytes) are formed, which is controlled by an interplay of transcription factors, including members of the C/EBP, PPARgamma and ADD families. The knowledge of a growing number of genes and molecules implicated in these three types of processes and of their metabolic relationships is leading toward a molecular understanding of the body weight regulatory system, and is paving the way for new methods of obesity control, especially pharmacological but also nutritional and possibly involving genetic intervention.

Adipose Tissue↗

PubMed2004

Hsp70 and Hsp90--a relay team for protein folding.

Molecular chaperones are a functionally defined set of proteins which assist the structure formation of proteins in vivo. Without certain protective mechanisms, such as binding nascent polypeptide chains by molecular chaperones, cellular protein concentrations would lead to misfolding and aggregation. In the mammalian system, the molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins, like steroid hormone receptors, transcription factors, and kinases, some of which are involved in cancer progression. Hsp70 and Hsp90 form a multichaperone complex, in which both are connected by a third protein called Hop. The connection of and the interplay between the two chaperone machineries is of crucial importance for cell viability. This review provides a detailed view of the Hsp70 and Hsp90 machineries, their cofactors and their mode of regulation. It summarizes the current knowledge in the field, including the ATP-dependent regulation of the Hsp70/Hsp90 multichaperone cycle and elucidates the complex interplay and their synergistic interaction.

Adenosine Triphosphate↗