Search PubMed⌕ Search

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.

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

At least 19 recordsLinked to original sources
PubMed2025

Computational network biology analysis revealed COVID-19 severity markers: Molecular interplay between HLA-II with CIITA.

COVID-19, severe acute respiratory syndrome coronavirus 2, rapidly spread worldwide. Severe and critical patients are expected to rapidly deteriorate. Although several studies have attempted to uncover the mechanisms underlying COVID-19 severity, most have focused on the perturbations of single genes. However, the complex mechanism of COVID-19 involves numerous perturbed genes in a molecular network rather than a single abnormal gene. Thus, we aimed to identify COVID-19 severity-specific markers in the Japanese population using gene network analysis. In order to reveal the severity-specific molecular interplays, we developed a novel computational network biology strategy that measures dissimilarity between networks based on the comprehensive information of gene network (i.e., expression levels of genes and network structure) by using Kullback-Leibler divergence. Monte Carlo simulations demonstrated the effectiveness of our strategy for differential gene network analysis. We applied this method to publicly available whole blood RNA-seq data from the Japan coronavirus disease 2019 Task Force and identified differentially regulated molecular interplays between 368 severe and 105 non-severe samples. Our analysis suggests the gene network between HLA class II, CIITA, and CD74 as a COVID-19 severity specific molecular marker. Although the association between HLA class II and COVID-19 has been demonstrated, our data analysis revealed that the molecular interplay of HLA class II with its target and/or regulator is a crucial marker for COVID-19 severity. Our findings from computational network biology analysis suggest that suppression and activation of the molecular interplay between HLA class II, CIITA, and CD74 provide crucial clues to uncover the mechanisms of COVID-19 severity.

Humans↗
PubMed1990

The effect of interplay interval on adjunctive behavior in humans in a game-playing situation.

Thirty-seven undergraduate students played two consecutive games of backgammon where manipulated interplay intervals were either 10, 22.5, 45, or 90 sec in length. When visual access to the opponent's play was blocked by a curtain during the second game, rates of movement, drinking, and eating increased over baseline rates prevailing in the first game. Grooming rate was not affected. Functions relating behavior rate to interplay interval were not bitonic for any of the behaviors; however, response distributions for drinking demonstrated postplay peaks at each interplay interval. Problems of classifying human behaviors into adjunctive versus faculatative categories were discussed.

Adolescent↗
PubMed2024

Sparse spectral graph analysis and its application to gastric cancer drug resistance-specific molecular interplays identification.

Uncovering acquired drug resistance mechanisms has garnered considerable attention as drug resistance leads to treatment failure and death in patients with cancer. Although several bioinformatics studies developed various computational methodologies to uncover the drug resistance mechanisms in cancer chemotherapy, most studies were based on individual or differential gene expression analysis. However the single gene-based analysis is not enough, because perturbations in complex molecular networks are involved in anti-cancer drug resistance mechanisms. The main goal of this study is to reveal crucial molecular interplay that plays key roles in mechanism underlying acquired gastric cancer drug resistance. To uncover the mechanism and molecular characteristics of drug resistance, we propose a novel computational strategy that identified the differentially regulated gene networks. Our method measures dissimilarity of networks based on the eigenvalues of the Laplacian matrix. Especially, our strategy determined the networks' eigenstructure based on sparse eigen loadings, thus, the only crucial features to describe the graph structure are involved in the eigenanalysis without noise disturbance. We incorporated the network biology knowledge into eigenanalysis based on the network-constrained regularization. Therefore, we can achieve a biologically reliable interpretation of the differentially regulated gene network identification. Monte Carlo simulations show the outstanding performances of the proposed methodology for differentially regulated gene network identification. We applied our strategy to gastric cancer drug-resistant-specific molecular interplays and related markers. The identified drug resistance markers are verified through the literature. Our results suggest that the suppression and/or induction of COL4A1, PXDN and TGFBI and their molecular interplays enriched in the Extracellular-related pathways may provide crucial clues to enhance the chemosensitivity of gastric cancer. The developed strategy will be a useful tool to identify phenotype-specific molecular characteristics that can provide essential clues to uncover the complex cancer mechanism.

Stomach Neoplasms↗
PubMed2026

The Multiple Roles of Genetics on Freshwater Macrophyte Functional Traits in the Interplay With the Environment: A Review.

The study of functional trait variation is increasingly used to understand macrophyte adaptation, as traits reflect organismal performance under different ecosystem conditions. Phenotypic expression results from the interplay of genetic and environmental factors: genetics provides the molecular basis for heritable traits and constrains potential phenotypes, while the environment acts as a selective and modulatory force. However, the genetic insight into traits has rarely been addressed in freshwater macrophyte studies. This review examines the different ways in which the DNA of macrophytes interplays with the environment and contributes to the variation in their functional traits, outlining main approaches, gaps, and future challenges. Only 21 studies explicitly combined genetics with functional traits and environment in the last fifteen years. The most common approach was the use of common garden experiments to explore acclimation and adaptation in a few model species. Current studies mainly focus on morphological and growth traits that best describe macrophytes' economic strategies, with limited attention to other trait categories, while the genetic and DNA traits studied are more variable. Across studies, environmental factors generally explained a larger proportion of functional trait variation, highlighting the dominant role of phenotypic plasticity for macrophyte acclimatation, whereas genetic contribution increased under experimentally manipulated conditions. Genome size and epigenetic variation influenced phenotypic plasticity; however, the effect was different and inconsistent on traits and depended on phylogenetic relationships and geographical environment variation. In field studies of natural populations, life history traits and hydrology had a strong effect on the geographic distribution of genetic diversity and the response to selection, as well as on our ability to distinguish selection from genetic drift. Future research should enhance molecular analyses, adopt multifactorial and long-term experimental designs, develop conceptual frameworks to address the relationships between genomics, environment and functional traits and integrate emerging tools to capture macrophyte adaptation better.

adaptation↗
PubMed2026

The interplay of epigenetic remodelling and transposon-mediated genomic instability in ageing and longevity.

Ageing and age-related diseases are the result of complex biological processes that progressively cause deterioration of cellular and tissue function. Among the key hallmarks of ageing are epigenetic alterations and genomic instability, both of which are closely interconnected and significantly contribute to the ageing process. The epigenome, encompassing both DNA and histone modifications, regulates gene expression and maintains genomic integrity throughout life. With age, these regulatory systems become dysregulated, leading to genome-wide changes in chromatin structure, histone modifications and the reactivation of transposable elements (TEs). TEs, typically silenced in heterochromatic regions, become active in aged cells, contributing to genomic instability, mutagenesis, inflammation and metabolic disruption. Despite their significant implications, the role of TEs in the ageing process remains underexplored, and the interplay between epigenomic remodelling and TE activity remains poorly understood. In this review, we explore the molecular mechanisms underlying epigenetic alterations and TE reactivation during ageing, the impact of these changes on genomic stability and the potential therapeutic interventions targeting this interplay. By deciphering the role of epigenetic modifications and TE derepression in the ageing process, we aim to highlight novel avenues for anti-ageing and pro-longevity strategies.

Aging↗
PubMed1984

Interaction of calmodulin with muscle phosphofructokinase. Interplay with metabolic effectors of the enzyme under physiological conditions.

The hysteretic calmodulin-induced inactivation of muscle phosphofructokinase and the calmodulin-mediated reactivation are essentially dependent on environmental conditions. The interplay of calmodulin during these reactions and at allosteric conditions with Mg . ATP, fructose 6-phosphate, adenosine 5'-[beta, gamma-imido]triphosphate and with the allosteric effectors AMP, ADP, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate and glucose 1,6-bisphosphate was studied by two techniques. (a) A two-step technique with a preincubation of enzyme, calmodulin and effectors in close to physiological concentrations before dilution into an optimal activity assay. It reveals aggregation and slowly reversible conformation changes. (b) A direct assay of dilute enzyme at allosteric conditions. Dominating in the interplay of calmodulin with metabolic effectors is the competitive-like action of calmodulin on Mg . ATP binding to the regulatory sites of the enzyme. At high enzyme concentrations in the absence of hexose phosphates, i.e. at noncatalytic conditions calmodulin counteracts the stabilization of the highly active tetrameric form caused by Mg . ATP. In the allosteric assay it counteracts the ATP-induced allosteric inhibition. In both cases calmodulin acts synergistic with AMP and ADP. To a minor degree calmodulin also counteracts the stabilization of the tetrameric form caused by fructose 6-phosphate and hexose bisphosphate, now however antagonistically to AMP and ADP. By the demonstrated interactions the enzyme can be slowly and hysteretically shifted between an active tetrameric and an inactive dimeric state under control metabolic conditions and of Ca2+ and calmodulin. Resting conditions will inactivate and high contractile activity reactivate available enzyme.

Adenosine Triphosphate↗
PubMed1976

The interplay between target organ concentrations of lymphocytic choriomeningitis virus and cell mediated immunity in baby mice.

Circumstantial evidence has been presented which supports the view that the fatal LCM virus infection is due to an immunological conflict in the host animal. Hitherto, this outcome of the infection has only been observed in intracerebrally infected mice. In the present study, the intraperitoneal infection in young mice was investigated and the results revealed a new example of this immunological conflict. In mice infected a few days after birth, concentrations of the virus in the brain are high, while the CMI response is non-measurable. If the infection is induced when the mice are 28 days old or more, there is little virus in the CNS, but a strong CMI response can be demonstrated. All the mice in these two age groups survive. If mice are infected when they are 17-19 days old, however, they raise a moderate CMI response nine days after infection and, at the same time, their brains contain virus in high titres. The mortality among mice infected at this age is 100%, indicating that this combination is fatal. The lives of these animals can be saved by anti theta serum or if they are transplanted with syngeneic lymphoid cells sensitized to LCM virus. Our results strongly suggest an interplay between, on the one hand, the spread and the magnitude of the virus infection in the brain and, on the other, the cell mediated immune response. This interplay seems to be decisive for the clinical outcome of the LCM infection in mice.

Age Factors↗
PubMed2026

Methods for modeling gene-environment interplay using polygenic risk scores.

Polygenic risk scores (PRS) are increasingly recognized as pivotal tools for quantifying disease risk through the aggregation of multiple genetic variants. As sample sizes in genome-wide association studies (GWAS) continue to expand and PRS become more powerful, they are set to play a key role in translational research and personalized medicine. Understanding the interplay of PRS with environmental factors is critical for interpreting and applying PRS in diverse contexts. This interplay manifests in two forms: PRS-by-environment interaction (PRS × E) and gene-environment correlation (rGE). However, despite the growing application and importance of PRS, there are limited guidelines for performing PRS × E interaction analyses while controlling for rGE, which can lead to inconsistencies across studies and misinterpretation of results. Here we provide a review of different methods for performing PRSxE interaction in various epidemiological study designs, propose recommendations for best-practice, and discuss future challenges.

Gene-Environment Interaction↗
PubMed2026

Interplay between DNA and RNA methylation shapes cancer cell plasticity.

Cellular plasticity refers to the ability of healthy cells to shift between phenotypic states and modify their characteristics to maintain tissue homeostasis and integrity. In the tumor context, cancer stem cells (CSCs) exploit this flexibility to withstand stress, facilitate tumor dissemination, and evade therapeutic interventions. Epigenetic regulation, particularly DNA methylation at CpG sites, is recognized as a well-known driver of tumor plasticity by repressing differentiation programs through modulation of chromatin accessibility. More recently, RNA modifications (epitranscriptomics) have emerged as crucial post-transcriptional regulators of gene expression that shape RNA fate and function. Among these, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G) contribute to the regulation of cell identity by modulating stemness-differentiation balance, stress adaptation, and epithelial-to-mesenchymal transition (EMT). Notably, dysregulation of both DNA and RNA methylation signatures is frequently observed in tumors, suggesting potential functional interactions between these regulatory layers. Emerging evidence indicates that DNA CpG methylation and RNA methylation pathways may cooperate to influence stemness, survival, and EMT-associated signaling, thereby supporting CSCs' plasticity. Although the molecular mechanisms underlying this crosstalk remain incompletely understood, accumulating studies suggest that DNA and RNA methylation could converge within interconnected regulatory networks that contribute to the control of cancer cell identity. A deeper understanding of these interactions may uncover novel vulnerabilities for targeting tumor plasticity. In this review, we summarize the current knowledge on the interplay between DNA and RNA methylation in regulating tumor plasticity, highlighting emerging mechanistic insights, functional interactions, and potential implications for future epigenetic and epitranscriptomic therapeutic strategies.

Humans↗
PubMed1992

Tyrosine phosphatases and their possible interplay with tyrosine kinases.

Protein tyrosine phosphatases represent a new family of intracellular and receptor-linked enzymes. They are totally specific toward tyrosyl residues in proteins, and, with specific activities 10-1000-fold greater than those of the protein tyrosine kinases, they can be expected to tightly control the level of phosphotyrosine within the cell. Most transmembrane forms contain two conserved intracellular catalytic domains, as displayed by the leukocyte common antigen CD45, but highly variable external segments. Some are related to the neuronal cell adhesion molecules (NCAMs) or fasciclin II and others contain fibronectin III repeats; this suggests that these enzymes might be involved in cell-cell interaction. The intercellular enzymes appear to contain a highly conserved catalytic core linked to a regulatory segment. Deletion of the regulatory domain alters both substrate specificity and cellular localization. Likewise, overexpression of the full-length and truncated enzymes affects cell cycle progression and actin filament stability, respectively. The interplay between tyrosine kinases and phosphatases is considered. A hypothesis is presented suggesting that in some systems phosphatases might act synergistically with the kinases and elicit a physiological response, irrespective of the state of phosphorylation of the target protein.

Animals↗
PubMed1990

A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients.

Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.

Complement Activation↗
PubMed1991

Implications for persistent chlamydial infections of phagocyte-microorganism interplay.

In vitro models of Chlamydia trachomatis inhibition by cytokines, human-monocyte derived macrophages (HMDM) and human polymorphonuclear leukocytes (HPMN) are discussed in an attempt to delineate the molecular basis of parasite-host cell interplay in persistent and chronic chlamydial infection. Interferon gamma (IFN) has been found to reversibly inhibit chlamydial growth at an early stage in the replicative cycle, while tumor necrosis factor (TNF) has a more profound effect on chlamydial growth resulting in production of aberrant reticulate bodies and enhancement of production of prostaglandin E2 (PGE2). Chlamydia trachomatis (serovar L2) replicate in HMDM while serovar K has been found to be restricted in these cells. Chlamydiae are killed by HPMN but the cell walls persist undegraded, inducing production of oxygen radicals which can be demonstrated to induce DNA strand scissions in HeLa target cells. Evidence is accumulating that chlamydia specific serum IgA antibodies may serve as a noninvasive serological marker for diagnosis of a number of acute and persistent Chlamydia trachomatis infections.

Chlamydia Infections↗
PubMed1991

High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group.

PURPOSE AND PATIENTS: We measured the serum concentrations of interleukin-6 (IL-6) in 70 patients with established septic shock caused predominantly by gram-negative bacteria. The aims of the study were to determine whether and for how long IL-6 was detectable in the circulation of these patients, to assess whether IL-6 levels were associated with patients' outcomes, and, finally, to examine the interplay between IL-6, tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma). RESULTS: IL-6 was detected in 64% of the patients at study entry but in only 18% on Day 1 and 2% on Day 10. Serum levels of IL-6 were higher (median: 3.5 ng/mL, range: less than 0.1 to 305 ng/mL) in patients dying of fulminant septic shock than in those surviving (median: 0.5 ng/mL, range: less than 0.1 to 135 ng/mL; p = 0.003) or in those with a transient reversal of shock but who ultimately died of a relapse of shock (median: less than 0.1 ng/mL, range: less than 0.1 to 12.5 ng/mL; p = 0.005). However, no cutoff values of IL-6 confidently predicted the outcome of an individual patient. The serum concentrations of IL-6 measured at study entry correlated with the duration of survival (r = -0.51, p = 0.004) and with the levels of TNF-alpha (r = 0.53; p less than 0.0001) but not with the levels of either IL-1 beta (r = 0.01, p = 0.90) or IFN-gamma (r = 0.06, p = 0.60). CONCLUSIONS: These results indicate that circulating levels of IL-6 are detectable in a majority of patients with gram-negative septic shock. Concentrations of IL-6 peaked near the onset of shock and rapidly decreased to undetectable levels within approximately 24 hours in most patients. Levels of IL-6 measured at study entry correlated with levels of TNF and with patients' outcomes. Yet, IL-6 does not appear to be a clinically useful laboratory test for predicting the outcome of an individual patient.

Adolescent↗
PubMed1988

Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation.

Reduced glutathione (GSH) delays microsomal lipid peroxidation via the reduction of vitamin E radicals, which is catalyzed by a free radical reductase (Haenen, G.R.M.M. et al. (1987) Arch. Biochem. Biophys. 259, 449-456). Lipoic acid exerts its therapeutic effect in pathologies in which free radicals are involved. We investigated the interplay between lipoic acid and glutathione in microsomal Fe2+ (10 microM)/ascorbate (0.2 mM)-induced lipid peroxidation. Neither reduced nor oxidized lipoic acid (0.5 mM) displayed protection against microsomal lipid peroxidation, measured as thiobarbituric acid-reactive material. Reduced lipoic acid even had a pro-oxidant activity, which is probably due to reduction of Fe3+. Notably, protection against lipid peroxidation was afforded by the combination of oxidized glutathione (GSSG) and reduced lipoic acid. It is shown that this effect can be ascribed completely to reduction of GSSG to GSH by reduced lipoic acid. This may provide a rationale for the therapeutic effectiveness of lipoic acid.

Animals↗
PubMed1992

Loneliness and alcohol abuse: a review of evidences of an interplay.

This report contains a review of the literature about the interplay between loneliness and the abuse of alcohol. A theoretical discussion based on clinical observations can be dated back to the 1950's. Systematic empirical studies, however, appear sparsely and have mainly been performed during the last decade. Thus, knowledge is still incomplete, but the review indicates that loneliness may be significant at all stages in the course of alcoholism: as a contributing and maintaining factor in the growth of abuse and as an encumbrance in attempts to give it up. Concordant reports demonstrate that alcoholics do feel more lonely than members of most other groups do. In advanced abusers, loneliness is obviously connected with a number of negative characteristics and, together with several of those, directly linked to a poor prognosis. There are, however, no obvious relations to the external social situation (i.e. network) or amount of drinking. Instead, the feeling of loneliness appears to be more connected with a general negative perception about oneself and one's relations to other people and also with a general dissatisfaction with most things in life. The lonely abuser seems likewise resigned and unable to bring himself to change his/her situation. There are also associations with a broad array of psychopathology. In comparison to people with other health problems, the supportive value of the social network of alcoholics appears to be more wavering.

Alcoholism↗
PubMed2016

The impact of metagenomic interplay on the mosquito redox homeostasis.

Mosquitoes are exposed to oxidative challenges throughout their life cycle. The primary challenge comes from a blood meal. The blood digestion turns the midgut into an oxidative environment, which imposes pressure not only on mosquito fecundity and other physiological traits but also on the microbiota in the midgut. During evolution, mosquitoes have developed numerous oxidative defense mechanisms to maintain redox homeostasis in the midgut. In addition to antioxidants, SOD, catalase, and glutathione system, sufficient supply of the reducing agent, NADPH, is vital for a successful defense against oxidative stress. Increasing evidence indicates that in response to oxidative stress, cells reconfigure metabolic pathways to increase the generation of NADPH through NADP-reducing networks including the pentose phosphate pathway and others. The microbial homeostasis is critical for the functional contributions to various host phenotypes. The symbiotic microbiota is regulated largely by the Duox-ROS pathway in Drosophila. In mosquitoes, Duox-ROS pathway, heme-mediated signaling, antimicrobial peptide production and C-type lectins work in concert to maintain the dynamic microbial community in the midgut. Microbial mechanisms against oxidative stress in this context are not well understood. Emerging evidence that microbial metabolites trigger host oxidative response warrants further study on the metagenomic interplay in an oxidative environment like mosquito gut ecosystem. Besides the classical Drosophila model, hematophagous insects like mosquitoes provide an alternative model system to study redox homeostasis in a symbiotic metagenomic context.

Animals↗
PubMed1983

Reverse transcriptase and its associated ribonuclease H: interplay of two enzyme activities controls the yield of single-stranded complementary deoxyribonucleic acid.

The synthesis of single-stranded globin cDNA by the RNA-directed DNA polymerase activity of reverse transcriptase in the presence of oligothymidylate primers was investigated in order to determine the limitations to higher yields. The results indicated that the associated ribonuclease H activity, an integral part of reverse transcriptase, plays a large role in the synthesis of the first strand of cDNA and that the interplay of the two enzyme activities for any specific set of conditions determines the yield of single-stranded products. In both the presence and the absence of polymerization, the associated ribonuclease H catalyzed the deadenylation of mRNA, producing molecules that were somewhat shorter, highly homogeneous in size, and fully translatable into globin protein. They were also entirely lacking in the ability to serve as templates for cDNA synthesis. The reaction was completely dependent on oligothymidylate and completely independent of deoxyribonucleoside triphosphates. The initial rate of deadenylation was one-fourth the initial rate of initiation of polymerization when saturating levels of deoxyribonucleoside triphosphates were used in the polymerase reaction. In the presence of ribonuclease H activity, the DNA polymerase catalyzed the synthesis of an array of cDNAs including some that were full length. The initiation of polymerization was rate limiting: once synthesis had begun, it required 1-1.5 min to transcribe globin mRNA. However, most primers that were elongated were aborted prematurely. Maximum synthesis of full-length cDNA required stoichiometric levels of enzyme and high triphosphate levels, but regardless of conditions, the sum of completed cDNA and deadenylated mRNA accounted for only 50% of the input mRNA. The data fit a model in which synthesis of full-length cDNA molecules depends on the arrangement of primers and transcription initiation complexes on the poly(A) "tail" of mRNA.

Animals↗
PubMed1990

Interplay of advances between theory, research, and application in treatment interventions aimed at behavior problem children and adolescents.

This article examines the important role that the interplay between theory, research, and application has in fostering breakthroughs in the treatment of clinical problems. This issue is presented in the context of an ongoing program of psychotherapy research that targets for intervention Hispanic behavior problem youth and their families. Findings and breakthroughs in structural family therapy, the measurement of family and child psychodynamic functioning, the development of culturally appropriate interventions, the role of attrition as a measure of outcome, and the investigation of theoretically postulated mechanisms in behavior change are discussed. Recommendations for future research directions are made.

Adolescent↗