Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “molecular network”

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 145 records · Page 8Linked to original sources
PubMed2006

Cytoskeletal polymer networks: the molecular structure of cross-linkers determines macroscopic properties.

In living cells the mechanical properties of the actin cytoskeleton are defined by the local activation of different actin cross-linking proteins. These proteins consist of actin-binding domains that are separated and geometrically organized by different numbers of rod domains. The detailed molecular structure of the cross-linking molecules determines the structural and mechanical properties of actin networks in vivo. In this study, we systematically investigate the impact of the length of the spacing unit between two actin-binding domains on in vitro actin networks. Such synthetic cross-linkers reveal that the shorter the constructs are, the greater the elastic modulus changes in the linear response regime. Because the same binding domains are used in all constructs, only the differences in the number of rod domains determine their mechanical effectiveness. Structural rearrangements of the networks show that bundling propensity is highest for the shortest construct. The nonlinear mechanical response is affected by the molecular structure of the cross-linker molecules, and the observed critical strains and fracture stress increase proportional to the length of the spacing unit.

Actins↗
PubMed2003

Dichlorobis(2-chloro-5-methylpyridine-kappaN)copper(II).

In the crystals of the title compound, [CuCl(2)(C(6)H(6)ClN)(2)], the Cu atom lies on an inversion centre and is four-coordinated by two pyridine N atoms and two Cl atoms in trans positions. The coordination geometry is square planar, with Cu-N and Cu-Cl distances of 1.986 (2) and 2.2536 (11) A, respectively. The two pyridine rings are parallel, but twist from the CuN(2)Cl(2) coordination plane by about 95 degrees in the complex molecule. There are three kinds of intermolecular C-H.Cl hydrogen bonds in the crystals. Two of these types generate two-dimensional molecular networks, viewed in the direction of the a axis, and the other connects adjacent molecular networks.

Journal Article↗
PubMed2001

Report from the second international meeting of the Attention Deficit Hyperactivity Disorder Molecular Genetics Network.

Given evidence from twin, family, and adoption studies of genetic influence on attention deficit hyperactivity disorder (ADHD), a growing number of researchers have initiated molecular genetics studies to explore the influence of specific genes on this condition. In 1999, these investigators convened to discuss ways of sharing information and facilitating collaborations across research sites. Enthusiastic response to this first conference prompted an even larger group of investigators to come together this year. This recent meeting, held in London, began with a presentation of Hypescheme, an operational criteria checklist developed in an effort to promote the reliable communication of diagnostic and other relevant clinical information related to ADHD. The benefits and limitations of Hypescheme, as well as the continued challenges to collaboration, were discussed. A new ADHD-specific rating scale, developed to be of use in genetic analyses, was also presented. Focus then turned to collaborative projects proposed by investigators and practical suggestions regarding joint data analyses projects. Finally, new data from individual sites were presented. Because the mode of inheritance of ADHD is likely to be complex, efforts to collaborate and cross-validate findings remain an important priority for researchers studying the molecular genetics of this disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Antisense oligonucleotide drug design.

Maneuvering single gene expression is not only an optimal way to study gene function but also an ambitious goal, which will lead to the treatment of a variety of human diseases whose main pathogenetic event is a genetic alteration. The recent efforts focusing on the genome project have led to array based, high throughput, gene expression analysis techniques that allow the study of complex molecular networks. Combining these powerful new technologies with modulation of gene expressions is making it possible to unravel complex molecular networks or, vice versa, to find new gene products responsible for pathological conditions on which exogenous modulation can be productive. Efficient and specific modulation of gene expression can be obtained either by producing transgenic or gene knockout organisms or cells (gene targeting), or by treating organisms or cells with short synthetic nucleic acid segments in antisense orientation with respect to the targeted mRNAs (mRNA targeting by antisense strategy). While genome manipulation is a time consuming and expensive approach, requiring invasive intervention, the "antisense strategy" is characterized by high flexibility resulting from safeness, specificity, reversibility, modulability, and low cost. The rationale of the antisense strategy is that, once one gene sequence is known, its expression can be silenced by application of synthetic single-strand nucleic acid segments (oligonucleotides) whose sequence is in antisense orientation compared to the targeted mRNA. Recently, this "informational" strategy has been boosted by the discovery of the RNA interference: a natural mechanism by which cells are thought to fight detrimental exogenous viruses and endogenous transposons. Despite promising futures, antisense-based therapeutics are far from being an established reality. This review analyses the recent improvements in antisense-based gene expression modulation, focuses on the treatment of diseases in the light of the past, and provides our personal findings on this topic.

Animals↗
PubMed2026

Sanguinarine as a multi-target therapeutic candidate for laryngeal cancer: insights from network pharmacology, molecular dynamics and in vitro validation.

OBJECTIVE: To identify the core targets and elucidate the potential molecular mechanisms of sanguinarine (SA) against laryngeal squamous cell carcinoma (LSCC), and to validate its antitumor effects in vitro. METHODS: Potential targets of SA were predicted using SwissTargetPrediction, TargetNet, and SuperPred and intersected with LSCC-related targets obtained from the GeneCards, OMIM, and DISEASES databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed using the STRING database (combined score > 0.900), and topological parameters including degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EC), and local average connectivity (LAC) were calculated in Cytoscape to identify core genes based on median thresholds. Molecular docking and 100-ns molecular dynamics (MD) simulations were conducted for epidermal growth factor receptor (EGFR), Phosphatidylinositide-3-kinase catalytic subunit alpha (PIK3CA), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), and Non-Receptor Tyrosine Kinase (SRC). The effects of SA on LSCC were evaluated using CCK-8, colony formation, Transwell migration, and wound-healing assays in TU177 cells and TU212. RESULTS: A total of 213 common targets were identified, which were significantly enriched in PI3K-Akt signaling, EGFR tyrosine kinase inhibitor resistance, and adhesion- and migration-related pathways. The PPI network comprised 259 nodes and 259 edges, from which five core genes-PIK3CA, PIK3CB, PIK3CD, EGFR, and SRC-were identified. Molecular docking revealed strong binding affinities between SA and the PI3K family proteins (- 9.79 to - 10.96 kcal/mol), as well as EGFR (- 8.58 kcal/mol) and SRC (- 6.77 kcal/mol). MD simulations indicated greater stability of SA complexes with EGFR and PI3K family members compared with SRC. In vitro assays demonstrated that SA significantly inhibited TU177 cell and TU212 cell proliferation, colony formation, and migration. CONCLUSION: SA may exert anti-laryngeal cancer effects through synergistic multi-target inhibition centered on the EGFR/SRC/PI3K signaling axis, highlighting its potential as a promising therapeutic candidate for LSCC.

Humans↗
PubMed1996

Determination of collagen-proteoglycan interactions in vitro.

The objective of this study was to characterize the physical interactions of the molecular networks formed by mixtures of collagen and proteoglycan in vitro. Pure proteoglycan aggrecan solutions, collagen (type II) suspensions and mixtures of these molecules in varying proportions and concentrations were subjected to viscometric flow measurements using a cone-on-plate viscometer. Linear viscoelastic and non-Newtonian flow properties of these solutions and suspensions were described using a second-order statistical network theory for polymeric fluids (Zhu et al., 1991, J. Biomechanics 24, 1007-1018). This theory provides a set of material coefficients which relate the macroscopic flow behavior of the fluid to an idealized molecular network structure. The results indicated distinct differences between the flow properties of pure collagen suspensions and those of pure proteoglycan solutions. The collagen network showed much greater shear stiffness and more effective energy storage capability than the proteoglycan network. The relative proportion of collagen to proteoglycan is the dominant factor in determining the flow behavior of the mixtures. Analysis of the statistical network theory indicated that the collagen in a collagen-proteoglycan mixture enhances molecular interactions by increasing the amount of entanglement interactions and/or the strength of interaction, while aggrecan acts to reduce the number and/or strength of molecular interactions. These results characterize the physical interactions between type II collagen and aggrecan and provide some insight into their potential roles in giving articular cartilage its mechanical behavior.

Aggrecans↗
PubMed1987

Gelling agents.

The characteristic physical properties of food gels result from the ability of certain proteins and polysaccharides to form continuous three-dimensional molecular networks. Development of new products based on gels, and improvements to existing ones, require a basic understanding of the intermolecular forces by which network cross-linkages are formed and stabilized. In this review new methods for studying food gels are described. The mechanisms by which molecular networks are formed by the gelling agents most frequently used by the food industry are discussed, with emphasis on the role of the solvent (water) and added solutes such as salts and sugars. More complex mixed gelling systems are discussed in some detail because of their practical importance and recent significant developments in this area.

Chemical Phenomena↗
PubMed2006

Reflections on the European Union Eurythron Network Meeting "Molecular Control of Erythropoiesis," September 22-23, 2005, Istituto Superiore di Sanità, Rome, Italy.

Red blood cells (RBCs) mediate oxygen transport throughout the body, a function that is essential for life. RBCs are continuously produced via a process called erythropoiesis. Anemias (insufficient numbers of functional RBCs), caused by failure of erythropoiesis, are a major cause of disease worldwide. Hereditary anemias constitute the most common human genetic disorders; they have no effective cure yet. The European research training network Eurythron follows a multidisciplinary approach to clarify the important molecular mechanisms in normal and pathological erythropoiesis, with a view to develop novel therapies to cure the anemias. The aim is to generate a comprehensive molecular description of mechanisms governing specification of hematopoietic stem cells in embryogenesis, lineage commitment, differentiation, and postmitotic maturation of RBCs. We report on the Eurythron meeting in Rome, in which novel approaches in stem cell and erythroid cell biology, including in vitro expansion of primary cells, biochemistry of receptor/signal transduction complexes and transcription factors, and (epi)genetics, were discussed.

Animals↗
PubMed1996

Testing the efficacy of a molecular surveillance network: methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) genotypes in six hospitals in the metropolitan New York City area. The BARG Initiative Pilot Study Group. Bacterial Antibiotic Resistance Group.

Molecular fingerprinting techniques are rapidly becoming indispensable tools for hospital epidemiology. On the other hand, the relative complexity and unfamiliarity of these techniques to most hospital diagnostic laboratories limit their usefulness. In an attempt to provide a solution for this dilemma, we tested the feasibility and efficacy of a cooperative venture in which molecular typing of isolates recovered from patients in six hospitals was performed at two microbiology research laboratories with expertise in these techniques. In a small preliminary study, 30 methicillin-resistant Staphylococcus aureus (MRSA) and 30 vancomycin-resistant Enterococcus faecium (VREF) isolates were collected over a 3-week period from six hospitals in the metropolitan New York area and transported to the Laboratory of Microbiology at The Rockefeller University during the summer months of 1994. Nineteen of the 27 confirmed MRSA isolates were closely related strains carrying the same mecA and the same Tn554 polymorphs in a pulsed-field gel electrophoresis (PFGE) background represented by closely related subtypes of a single pattern, indicating the wide distribution of this MRSA clone among the participating hospitals. Typing of the same 27 MRSA isolates was also performed at the Tuberculosis Center of the Public Health Research Institute and identical results were obtained. The 29 confirmed VREF isolates were highly heterogeneous and belonged to as many as 23 distinct clonal types as defined by PFGE patterns and probing with vanA. Characterization of the 60 isolates by these methods was completed in one month of full-time effort by a single experienced laboratory assistant guided by a doctoral-level expert in molecular fingerprinting techniques. The collection of samples for both MRSA and VREF was not intended to address epidemiological questions but to determine the feasibility of a multicenter study. On the basis of our preliminary findings we are encouraged that a larger cooperative effort is possible and with the correct sampling method we believe that epidemiological and surveillance studies could be accomplished that would provide a tracking system to assist hospitals, clinics, and chronic care facilities in controlling the spread of multidrug-resistant pathogens.

Anti-Bacterial Agents↗
PubMed2005

Concluding remarks.

This meeting has well illustrated the state-of-the-art phenomenon of receptor-receptor interactions between heptaspanning membrane receptors (also named G protein-coupled receptors [GPCRs]), as both theoretical aspects and new experimental evidence have been discussed extensively.From a general standpoint the theoretical discussion has enlightened us to the phenomenon of receptor-receptor interactions as a "privileged window," which allows the exploration of some important structural and functional aspects of molecular networks (Agnati et al., this issue). Also, unexpected functions of well-known proteins can be studied, such as beta-arrestins, which are at the interface between horizontal and vertical molecular networks and have a signaling function of their own besides modulating receptor transduction and trafficking (Lefkowitz, this issue). The experimental data have shown that many in vitro approaches are now available to study the structure and function of homo- and hetero-oligomers in cell lines and primary cultures, making possible a major expansion of the field. However, the in vivo approaches to study the role of heteromeric receptor complexes in cell function have been less clear cut. It was discussed, especially by George, that one problem with receptor knockout mice is inter alia that the removal of one receptor will alter the balance of various homomeric and heteromeric receptor complexes in which the deleted receptor participated. In fact, each receptor might participate in a number of heteromeric receptor complexes. An attractive in vivo approach in the receptor-receptor interaction study will be to use knockin mice in which one receptor A (Ra) has been removed and replaced by a mutated A receptor (Ra'). Several different strategies can be considered, and here are some of them. 1. Ra' can still recognize its ligand and signal but does not interact with its usual heteromeric receptor partner B (Rb). Thus, Ra' operates as a monomer and/or homomer. 2. Ra' can still recognize its ligand and interact with Rb, but it cannot signal (e.g., it does not couple to the G protein). Thus, Ra' operates as a modulator protein of Rb. 3. Ra' can still recognize its ligand and signal, but it allosterically affects its heteromeric partner Rb in a different way. Thus, Ra' operates as an unusual modulator of Rb.

Animals↗
PubMed2026

Uncovering molecular regulatory networks of low-temperature stress response in Trachinotus ovatus via integrated transcriptome and metabolome analyses.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.

Animals↗
PubMed2005

CaV2.3 channel and PKClambda: new players in insulin secretion.

Insulin secretion is critically dependent on the proper function of a complex molecular network. Ca(V)2.3-knockout (Ca(V)2.3(-/-)) and PKClambda-knockout (PKClambda(-/-)) mouse models now suggest that these 2 players, the Ca(v)2.3 channel and PKClambda, are important constituents of this molecular network. Subsequent to glucose stimulation, insulin is released from the pancreatic beta cell in a biphasic pattern, i.e., a rapid initial phase followed by a slower, more sustained phase. Interestingly, Ca(2+) influx through the Ca(V)2.3 channel regulates only the second phase of insulin secretion. PKClambda seems to enter the beta cell nucleus and in turn modulates the expression of several genes critical for beta cell secretory function. Studies by Hashimoto et al. and Jing et al. in this issue of the JCI set out to answer the question of why numerous isoforms of proteins with similar functions are present in the beta cell. This is important, since it has been difficult to understand the modulatory and/or regulatory roles of different isoforms of proteins in defined subcellular compartments and at various times during the secretory process in both beta cell physiology and pathophysiology.

Animals↗
PubMed2006

CellCircuits: a database of protein network models.

CellCircuits (http://www.cellcircuits.org) is an open-access database of molecular network models, designed to bridge the gap between databases of individual pairwise molecular interactions and databases of validated pathways. CellCircuits captures the output from an increasing number of approaches that screen molecular interaction networks to identify functional subnetworks, based on their correspondence with expression or phenotypic data, their internal structure or their conservation across species. This initial release catalogs 2019 computationally derived models drawn from 11 journal articles and spanning five organisms (yeast, worm, fly, Plasmodium falciparum and human). Models are available either as images or in machine-readable formats and can be queried by the names of proteins they contain or by their enriched biological functions. We envision CellCircuits as a clearinghouse in which theorists may distribute or revise models in need of validation and experimentalists may search for models or specific hypotheses relevant to their interests. We demonstrate how such a repository of network models is a novel systems biology resource by performing several meta-analyses not currently possible with existing databases.

Animals↗
PubMed2004

Impact of a disruption of a pathway delivering copper to mitochondria on Podospora anserina metabolism and life span.

A global depletion of cellular copper as the result of a deficiency in high-affinity copper uptake was previously shown to affect the phenotype and life span of the filamentous fungus Podospora anserina. We report here the construction of a strain in which the delivery of copper to complex IV of the mitochondrial respiratory chain is affected. This strain, PaCox17::ble, is a PaCox17-null mutant that does not synthesize the molecular chaperone targeting copper to cytochrome c oxidase subunit II. PaCox17::ble is characterized by a decreased growth rate, a reduction in aerial hyphae formation, reduced female fertility, and a dramatic increase in life span. The mutant respires via a cyanide-resistant alternative pathway, displays superoxide dismutase (SOD) activity profiles significantly differing from those of the wild-type strain and is characterized by a stabilization of the mitochondrial DNA. Collectively, the presented data define individual components of a molecular network effective in life span modulation and copper as an element with a dual effect. As a cofactor of complex IV of the respiratory chain, it is indirectly involved in the generation of reactive oxygen species (ROS) and thereby plays a life span-limiting role. In contrast, Cu/Zn SOD as a ROS-scavenging enzyme lowers molecular damage and thus positively affects life span. Such considerations explain the reported differences in life span of independent mutants and spread more light on the delicate tuning of the molecular network influencing biological ageing.

Amino Acid Sequence↗
PubMed2004

Pathway Miner: extracting gene association networks from molecular pathways for predicting the biological significance of gene expression microarray data.

UNLABELLED: We have developed a web-based system (Pathway Miner) for visualizing gene expression profiles in the context of biological pathways. Pathway Miner catalogs genes based on their role in metabolic, cellular and regulatory pathways. A Fisher exact test is provided as an option to rank pathways. The genes are mapped onto pathways and gene product association networks are extracted for genes that co-occur in pathways. The networks can be filtered for analysis based on user-selected options. AVAILABILITY: Pathway Miner is a freely available web accessible tool at http://www.biorag.org/pathway.html

Algorithms↗