[Analysis of the transcriptional regulatory network in the model organisms: yeast and sea urchin].
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Animals↗
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Network based approach identifies miR-145-3p as a central regulatory hub associated to the progression from localized to metastatic medullary thyroid carcinoma.
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from calcitonin producing C-cells and accounts for 1-5% of thyroid cancers. Total thyroidectomy is curative in localized disease (N0), whereas lymph node metastases (N1) are associated with poorer prognosis. However, the molecular mechanisms driving the metastatic shift remain poorly understood. This study aimed to identify miRNA features linked to metastatic spread in MTC, focusing on the transition from N0 to N1. Co-expression networks were constructed for N0 and N1 tumors, and differential connectivity analysis was used to identify key miRNAs acting as regulatory hubs. Functional annotation of their target genes was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome pathway analyses. Validation experiments were carried out in MTC cells to evaluate the effects of selected miRNAs on cell proliferation, survival, and MAPK pathway activation. Network analysis revealed distinct miRNA co-expression patterns between N0 and N1 tumors. Differential network analysis highlighted miR-145-3p as a central regulatory hub, exhibiting 29 altered co-expression changes and a marked loss of connectivity in N1. Target enrichment identified 59 validated genes, including key oncogenic drivers such as MYC, PTEN, BCL2, PIK3CA, AKT1, and MAPK7. In MTC cells, simultaneous inhibition of miR-145-3p together with its top co-expressed miRNAs increased proliferation and survival, and enhanced ERK phosphorylation, indicating MAPK pathway activation and a shift toward a more aggressive phenotype. In conclusion, this study identifies a miRNA regulatory hub centered on miR-145-3p that is associated with metastatic progression and highlights the value of network-based approaches in uncovering mechanisms of cancer dissemination. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
MAPK signaling↗
Epiluminescence microscopy-based classification of pigmented skin lesions using computerized image analysis and an artificial neural network.
Epiluminescence microscopy (ELM) is a non-invasive technique for in vivo examination which can provide additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). In the present study we attempt to determine whether PSLs can be automatically diagnosed by an integrated computerized system. This system should recognize the PSL, automatically extract features and use these features in training an artificial neural network, which should--if sufficiently trained--be capable of recognizing and classifying a new PSL without human aid. One hundred and twenty images of randomly selected histologically proven PSLs (33 common naevi, 48 dysplastic naevi and 39 malignant melanomas) were used in this study. The images were digitally obtained and the morphological features of the PSLs were extracted electronically without human assistance. The numerical data were then divided into learning and testing cases and linked to an artificial neural network for training and for further classification of lesions that the system had not been trained on. Our results show that the computerized system was able to automatically identify 95% of the PSLs presented. The sensitivity and specificity of the computerized system were 90% and 74% respectively. In contrast, when differentiating between individual types of lesions, the system performed at true positive rates of only 38% for malignant melanoma, 62% for dysplastic naevi and 33% for common naevi. Our data indicate that (1) ELM images of PSLs provide an excellent source for digital image analysis; (2) the vast majority of PSLs can be correctly identified by a relatively simple (and thus not "intelligent") application of digital image analysis; (3) automatic feature extraction based mainly on ABCD rules provides reliable data on the distinction between benign and malignant PSLs; and (4) there is evidence that artificial neural networks can be trained to adequately discriminate between benign and malignant PSLs.
Dysplastic Nevus Syndrome↗
Using networks to identify fine structural differences between functionally distinct protein states.
The vast increase in available data from the "-omics" revolution has enabled the fields of structural proteomics and structure prediction to make great progress in assigning realistic three-dimensional structures to each protein molecule. The challenge now lies in determining the fine structural details that endow unique functions to sequences that assume a common fold. Similar problems are encountered in understanding how distinct conformations contribute to different phases of a single protein's dynamic function. However, efforts are hampered by the complexity of these large, three-dimensional molecules. To overcome this limitation, structural data have been recast as two-dimensional networks. This analysis greatly reduces visual complexity but retains information about individual residues. Such diagrams are very useful for comparing multiple structures, including (1) homologous proteins, (2) time points throughout a dynamics simulation, and (3) functionally different conformations of a given protein. Enhanced structural examination results in new functional hypotheses to test experimentally. Here, network representations were key to discerning a difference between unliganded and inducer-bound lactose repressor protein (LacI), which were previously presumed to be identical structures. Further, the interface of unliganded LacI was surprisingly similar to that of the K84L variant and various structures generated by molecular dynamics simulations. Apo-LacI appears to be poised to adopt the conformation of either the DNA- or inducer-bound structures, and the K84L mutation appears to freeze the structure partway through the conformational transition. Additional examination of the effector binding pocket results in specific hypotheses about how inducer, anti-inducer, and neutral sugars exert their effects on repressor function.
Bacterial Proteins↗
The phylogeography and connectivity of the latitudinally widespread scleractinian coral Plesiastrea versipora in the Western Pacific.
Whereas terrestrial animal populations might show genetic connectivity within a continent, marine species, such as hermatypic corals, may have connectivity stretching to all corners of the planet. We quantified the genetic variability within and among populations of the widespread scleractinian coral, Plesiastrea versipora along the eastern Australian seaboard (4145 km) and the Ryukyu Archipelago (Japan, 681 km) using sequences of internal transcribed spacers (ITS1-2) from ribosomal DNA. Geographic patterns in genetic variability were deduced from a nested clade analysis (NCA) performed on a parsimony network haplotype. This analysis allowed the establishment of geographical associations in the distribution of haplotypes within the network cladogram, therefore allowing us to deduce phylogeographical patterns based under models of restricted gene flow, fragmentation and range expansion. No significant structure was found among Ryukyu Archipelago populations. The lack of an association between the positions of haplotypes in the cladogram with geographical location of these populations may be accounted for by a high level of gene flow of P. versipora within this region, probably due to the strong Kuroshio Current. In contrast, strong geographical associations were apparent among populations of P. versipora along the south-east coast of Australia. This pattern of restricted genetic connectivity among populations of P. versipora on the eastern seaboard of Australia seems to be associated with the present surface ocean current (the East Australian Current) on this side of the south-western Pacific Ocean.
Animals↗
Empirical analysis of an evolving social network.
Social networks evolve over time, driven by the shared activities and affiliations of their members, by similarity of individuals' attributes, and by the closure of short network cycles. We analyzed a dynamic social network comprising 43,553 students, faculty, and staff at a large university, in which interactions between individuals are inferred from time-stamped e-mail headers recorded over one academic year and are matched with affiliations and attributes. We found that network evolution is dominated by a combination of effects arising from network topology itself and the organizational structure in which the network is embedded. In the absence of global perturbations, average network properties appear to approach an equilibrium state, whereas individual properties are unstable.
Electronic Mail↗
Deciphering the role of individual acyl chains in the interaction network between phosphatidylserines and a single-spanning membrane protein.
PMP1 is a small single-spanning membrane protein functioning as a regulatory subunit of the yeast plasma membrane H(+)-ATPase. This protein forms a unique helix and exhibits a positively charged cytoplasmic domain that is able to specifically segregate phosphatidylserines (PSs). A marked groove formed at the helix surface is thought to play a major role in the related lipid-protein interaction network. Mutational analysis and (1)H NMR experiments were therefore performed on a synthetic PMP1 fragment using DPC-d(38) micelles as a membrane-like environment, in the presence of small amounts of POPS. A mutation designed for altering the helix groove was shown to disfavor the POPS binding specificity as much as that affecting the electrostatic interaction network. From POPS titration experiments monitored by a full set of one- and two-dimensional NOESY spectra, the association between the phospholipids and the PMP1 peptide has been followed. Our data reveal that the clustering of POPS molecules is promoted from a stabilized framework obtained by coupling the PMP1 helix groove to a POPS sn-2 chain. To our knowledge, the NOE-based titration plots displayed in this report constitute the first NMR data that directly distinguish the role of the sn-1 and sn-2 acyl chains in a lipid-protein interaction. The results are discussed while taking into account our accurate knowledge of the yeast plasma membrane composition and its ability to form functional lipid rafts.
Amino Acids↗
Longevity network: construction and implications.
The vast majority of studies on longevity have focused on individual genes/proteins, without adequately addressing the possible role of interactions between them. This study is the first attempt towards constructing a "longevity network" via analysis of human protein-protein interactions (PPIs). For this purpose, we (i) compiled a complete list of established longevity genes from different species, including those that most probably affect the longevity in humans, (ii) defined the human orthologs of the longevity genes, and (iii) determined whether the encoded proteins could be organized as a network. The longevity gene-encoded proteins together with their interacting proteins form a continuous network, which fits the criteria for a scale-free network with an extremely high contribution of hubs to the network connectivity. Most of them have never been annotated before in connection with longevity. Remarkably, almost all of the hubs of the "longevity network" were reported to be involved in at least one age-related disease (ARD), with many being involved in several ARDs. This may be one of the ways by which the proteins with multiple interactions affect the longevity. The hubs offer the potential of being primary targets for longevity-promoting interventions.
Aging↗
Multifunctional laryngeal motoneurons: an intracellular study in the cat.
We studied the patterns of membrane potential changes in laryngeal motoneurons (LMs) during vocalization, coughing, swallowing, sneezing, and the aspiration reflex in decerebrate paralyzed cats. LMs, identified by antidromic activation from the recurrent laryngeal nerve, were expiratory (ELMs) or inspiratory (ILMs) cells that depolarized during their respective phases in eupnea. During vocalization, most ELMs depolarized and most ILMs hyperpolarized. Some ILMs depolarized slightly during vocalization. During coughing, ELMs depolarized abruptly at the transition from the inspiratory to the expiratory phase. In one-third of ELMs, this depolarization persisted throughout the abdominal burst. In the remainder ("type A"), it was interrupted by a transient repolarization. ILMs exhibited a membrane potential trajectory opposite to that of type A ELMs during coughing. During swallowing, the membrane potential of ELMs decreased transiently at the onset of the hypoglossal burst and then depolarized strongly during the burst. ILMs hyperpolarized sharply at the onset of the burst and depolarized as hypoglossal activity ceased. During sneezing, ELMs and ILMs exhibited membrane potential changes similar to those of type A ELMs and ILMs during coughing. During the aspiration reflex, ELMs and ILMs exhibited bell-shaped hyperpolarization and depolarization trajectories, respectively. We conclude that central drives to LMs, consisting of complex combinations of excitation and inhibition, vary during vocalization and upper airway defensive reflexes. This study provides data for analysis of the neuronal networks that produce these various behaviors and analysis of network reorganization caused by changes in dynamic connections between the respiratory and nonrespiratory neuronal networks.
Animals↗
Untangling long branches: identifying conflicting phylogenetic signals using spectral analysis, neighbor-net, and consensus networks.
Long-branch attraction is a well-known source of systematic error that can mislead phylogenetic methods; it is frequently invoked post hoc, upon recovering a different tree from the one expected based on prior evidence. We demonstrate that methods that do not force the data onto a single tree, such as spectral analysis, Neighbor-Net, and consensus networks, can be used to detect conflicting signals within the data, including those caused by long-branch attraction. We illustrate this approach using a set of taxa from three unambiguously monophyletic families within the Pelecaniformes: the darters, the cormorants and shags, and the gannets and boobies. These three families are universally acknowledged as forming a monophyletic group, but the relationship between the families remains contentious. Using sequence data from three mitochondrial genes (12S, ATPase 6, and ATPase 8) we demonstrate that the relationship between these three families is difficult to resolve because they are separated by a short internal branch and there are conflicting signals due to long-branch attraction, which are confounded with nonhomogeneous sequence evolution across the different genes. Spectral analysis, Neighbor-Net, and consensus networks reveal conflicting signals regarding the placement of one of the darters, with support found for darter monophyly, but also support for a conflicting grouping with the outgroup, pelicans. Furthermore, parsimony and maximum-likelihood analyses produced different trees, with one of the two most parsimonious trees not supporting the monophyly of the darters. Monte Carlo simulations, however, were not sensitive enough to reveal long-branch attraction unless the branches are longer than those actually observed. These results indicate that spectral analysis, Neighbor-Net, and consensus networks offer a powerful approach to detecting and understanding the source of conflicting signals within phylogenetic data.
Animals↗
Action potential classifiers: a functional comparison of template matching, principal components analysis and an artificial neural network.
Multiunit neural activity occurs often in electrophysiological studies when utilizing extracellular electrodes. In order to estimate the activity of the individual neurons each action potential in the recording must be classified to its neuron of origin. This paper compares the accuracy of two traditional methods of action potential classification--template matching and principal components--against the performance of an artificial neural network (ANN). Both traditional methods use averages of action potential shapes to form their corresponding classifiers while the artificial neural network 'learns' a nonlinear relationship between a set of prototype action potentials and assigned classes. The set of prototypic action potentials and the assigned classes is termed the training set. The training set contained action potentials from each class which exhibited the full range of amplitude variability. The ANN provided better classification results and was more robust in analysis of across-animal data sets than either of the traditional action potential classification methods.
Action Potentials↗
Global asymptotic stability analysis of bidirectional associative memory neural networks with time delays.
This paper presents a sufficient condition for the existence, uniqueness and global asymptotic stability of the equilibrium point for bidirectional associative memory (BAM) neural networks with distributed time delays. The results impose constraint conditions on the network parameters of neural system independently of the delay parameter, and they are applicable to all continuous nonmonotonic neuron activation functions. It is shown that in some special cases of the results, the stability criteria can be easily checked. Some examples are also given to compare the results with the previous results derived in the literature.
Algorithms↗
Isoleucine uptake in Corynebacterium glutamicum ATCC 13032 is directed by the brnQ gene product.
By complementation analysis of an isoleucine-uptake-deficient Escherichia coli strain, it was shown that a 1.6-kb HindIII-StuI fragment of Corynebacterium glutamicum ATCC 13032, located downstream of the aecD gene, encodes an isoleucine uptake system. Sequence analysis revealed that the complementing fragment carried an open reading frame, termed brnQ, that encodes a protein with sequence similarities to branched-chain amino acid carriers of gram-positive and gram-negative bacteria. The brnQ gene specifies a predominantly hydrophobic protein of 426 amino acid residues with a calculated molecular mass of 44.9 kDa. A topology prediction by neural network computer analysis suggests the existence of 12 hydrophobic segments that most probably form transmembrane alpha-helices. A C. glutamicum mutant strain harboring a defined deletion of brnQ in the chromosome showed a considerably lower isoleucine uptake rate of 0.04 nmol min-1 mg (dry mass)-1 as compared to the wild-type strain rate of 1.2 nmol min-1 mg (dry mass)-1. Overexpression of brnQ by means of a tac promotor resulted in an elevated uptake rate for isoleucine of 11.3 nmol min-1 mg (dry mass)-1. Evidently, the brnQ gene encodes the only transport system in C. glutamicum directing isoleucine uptake.
Amino Acid Sequence↗
Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis.
Osteoporosis is a disease characterized by bone volume loss and architectural deterioration. The majority of work aimed at evaluating the structural implications of the disease has been performed based on stereologic analysis of histomorphometric sections. Only recently noninvasive imaging methods have emerged that provide sufficient resolution to resolve individual trabeculae. In this article, we apply digital topological analysis (DTA) to magnetic resonance microimages (mu-MRI) of the radius obtained at 137 x 137 x 350 microm3 voxel size in a cohort of 79 women of widely varying bone mineral density (BMD) and vertebral deformity status. DTA is a new method that allows unambiguous determination of the three-dimensional (3D) topology of each voxel in a trabecular bone network. The analysis involves generation of a bone volume fraction map, which is subjected to subvoxel processing to alleviate partial volume blurring, followed by thresholding and skeletonization. The skeletonized images contain only surfaces, profiles, curves, and their mutual junctions as the remnants of trabecular plates and rods after skeletonization. DTA parameters were compared with integral BMD in the lumbar spine and femur as well as MR-derived bone volume fraction (BV/TV). Vertebral deformities were determined based on sagittal MRIs of the spine with a semiautomatic method and the number of deformities counted after threshold setting. DTA structural indices were found the strongest discriminators of subjects with deformities from those without deformities. Subjects with deformities (n = 29) had lower topological surface (SURF) density (p < 0.0005) and surface-to-curve ratio (SCR; a measure of the ratio of platelike to rodlike trabeculae; p < 0.0005) than those without. Profile interior (PI) density, a measure of intact trabecular rods, was also lower in the deformity group (p < 0.0001). These data provide the first in vivo evidence for the structural implications inherent in postmenopausal osteoporosis accompanying bone loss, that is, the conversion of trabecular plates to rods and disruption of rods due to repeated osteoclastic resorption.
Adult↗
Rheology of hydroxyethylated starch aqueous systems. Analysis of gel formation.
This paper reports dynamic viscoelastic and steady shear measurements of aqueous solutions of two commercial hydroxyethyl ethers of potato starch, allowing us to define three different viscoelastic regions, depending on the polymer concentrations. The fluid-like zone (I) corresponds to a homogeneous solution, free of associations between chains, where the linear viscoelastic model can be applied; the fluid-gel transition zone (II) is associated with the rheology of complex systems which possess intermolecular specific interactions; and the gel-like zone (III) involves a network formation giving rise to a gel. The reversibility of the hydrogels was studied by means of steady/dynamic transient experiments allowing breakdown of the gel network and analysis of rehealing. Comparing the elastic moduli of the starch derivative gels leads us to assume that the functionality depends on the capacity to form hydrogen-bonding associations between polymer chains.
Elasticity↗
Building strong networks eight ways.
It is becoming common in healthcare institutions that the charter of Information Services goes beyond providing data. IS often needs to empower the user community with the right information and the right tools, which enable them to perform their jobs more efficiently and effectively. Creating such an infrastructure requires an information network, one that allows information to flow at all levels within and outside the facility. This fortifies and enhances the business process and enables institutions to function efficiently and profitably. But developing such an information network requires analysis and planning. The following eight steps detail considerations you should make to ensure the creation of an infrastructure robust enough to address the needs of today, and capable of incorporating technologies that might be required in the future.
Computer Communication Networks↗
Genotyping and coalescent phylogenetic analysis of Pneumocystis jiroveci from South Africa.
Sequence analysis of Pneumocystis jiroveci internal transcribed spacer (ITS) regions has become an important epidemiological tool. The objectives of the present study were to investigate sequence variations in the ITS1-5.8S ribosomal DNA (rDNA)-ITS2 regions; determine the P. jiroveci genotypes present in Cape Town, South Africa; and resolve the lineage evolution of the types by use of the coalescent theory. ITS regions were amplified from samples collected from 19 patients. PCR products were cloned, and four to five clones were sequenced from each specimen. Statistical parsimony was applied for coalescence-based network genotype analysis. The most prevalent type was Eg (14 of 19 patients, 33 of 83 clones), followed by Gg (4 of 19 patients, 7 of 83 clones), Eu (3 of 19 patients, 5 of 83 clones), and Gh (2 of 19 patients, 2 of 83 clones). Four new combinations (Eo, Je, Ge, and No), 11 new ITS1 sequences, and 13 new ITS2 sequences were identified. A new ITS2 type was detected in three patients and was designated type u. Coinfection appeared to be common, with 15 of 19 patients harboring more than one type and with up to six types per specimen. The resultant parsimony network identified Eg as the most probable ancestral haplotype and supported the occurrence of recombinational events within the population studied. Although the 5.8S rDNA region revealed only 13 clones containing one to two nucleotide polymorphisms, it may assist in defining types. Coalescent theory proposed that Eg is an ancestral type from which microevolutionary subtypes radiate.
AIDS-Related Opportunistic Infections↗
Air pollution and acute respiratory diseases in children: regression analysis of morbidity data.
The aim of this study was to investigate the relationship between acute respiratory diseases and the air quality in the urban area of the Upper Silesian Industrial Zone during autumn and winter with special emphasis on temporal variability in the air concentrations of pollutants. The survey was carried out in 5 primary care units in Chorzów where the morbidity data on the selected respiratory diseases were collected from 1 November 1992 to 31 March 1993. The air pollution data were obtained from the monitoring station, being a part of the Sanitary and Epidemiological Station Network. Regression analysis with mean values of concentrations of air pollutants as explanatory variables revealed a positive effect of combined suspended particulate matter and SO2 concentration on the increased prevalence of bronchitis and bronchiolitis. Similar and even stronger effect was observed at the level of temporal variability coefficients of the air pollutants. A hypothesis that temporal variability of the air concentration of pollutants might be a more relevant factor for determining the prevalence of respiratory diseases than simple mean values of the pollutant concentrations is very interesting worthy of further investigations.
Acute Disease↗