Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “network analysis”

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 919 records · Page 51Linked to original sources
PubMed2024

Muscle Tissue Transcriptome of Idiopathic Inflammatory Myopathy Reflects the Muscle Damage Process by Monocytes and Presence of Skin Lesions.

OBJECTIVE: We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl transfer RNA synthetase antibodies in the patients with DM (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and negative monocytes and myeloid dendritic cells. Notably, patients with DM demonstrated enrichment of complement and interferon-α and γ pathway genes compared with those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and the transforming growth factor-β signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathologic differences among IIM subtypes. DM was characterized by complement and interferon-α and γ signaling, whereas ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.

Humans↗
PubMed2026

A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases.

OBJECTIVE: The unknown pathophysiology and the lack of specific features for systemic juvenile idiopathic arthritis and adult-onset Still disease (collectively known as Still disease; SD) delay diagnosis and appropriate treatment. The goal of this study was to identify features and mechanisms that distinguish SD from other systemic autoinflammatory diseases (SAID). METHODS: Using the SomaScan assay and RNA sequencing (RNA-Seq), we determined the plasma proteomes and immune cell microRNA (miRNA) and RNA transcriptomes of 372 patients with SAID, respectively. Proteomic findings were validated by enzyme-linked immunosorbent assays. SD (n = 72) and non-SD SAIDs (n = 300) were compared to identify distinguishing features of SD. We performed integrated and unbiased analyses of all data sets using weighted gene correlation network analysis to identify feature modules that characterize SD and stratify patients. RESULTS: Elevated plasma heme oxygenase 1 (HO-1) and interleukin-18 (IL-18) strongly correlate and characterize SD but do not associate with general inflammation. SD was characterized by ferroptosis in plasma, type I interferon (IFN) signaling in monocyte transcriptomes, and elevated natural killer cell miRNA-146a-5p, which is an IL-18 induced miRNA. Finally, we identified feature modules that distinguish SD from other SAIDs and stratified patients with SD into two distinct subgroups not attributable to disease activity or inflammation but hemophagocytosis. CONCLUSION: This unprecedented large omics data set of SAIDs revealed that complex interactions among hemophagocytosis, IL-18, and type I IFN signaling characterize SD. Furthermore, two distinct subgroups in patients with SD were distinguished by the degree of hemophagocytic activity. Finally, the large proteomics and RNA-Seq data sets generated in this study can serve as an invaluable resource for the further investigation of SD and other SAIDs.

Humans↗
PubMed2002

Aerobic glucose metabolism of Saccharomyces kluyveri: growth, metabolite production, and quantification of metabolic fluxes.

The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0.29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate pathway cannot provide the cell with enough NADPH for biomass formation which is why the remaining NADPH will have to be provided by another pathway. During batch cultivation of S. kluyveri the tricarboxylic acid cycle was working as a cycle with a considerable flux, that is in sharp contrast to what has previously been observed in S. cerevisiae at the same growth conditions, where the tricarboxylic acid cycle operates as two branches. This indicates that the respiratory system was not significantly repressed in S. kluyveri during batch cultivation on glucose.

Acetates↗
PubMed2005

Noise in a Small Genetic Circuit that Undergoes Bifurcation.

Based on the consideration of Boolean dynamics, it has been hypothesized that cell types may correspond to alternative attractors of a gene regulatory network. Recent stochastic Boolean network analysis, however, raised the important question concerning the stability of such attractors. In this paper a detailed numerical analysis is performed within the framework of Langevin dynamics. While the present results confirm that the noise is indeed an important dynamical element, the cell type as represented by attractors can still be a viable hypothesis. It is found that the stability of an attractor depends on the strength of noise related to the distance of the system to the bifurcation point and it can be exponentially stable depending on biological parameters.

Journal Article↗
PubMed2001

Effect of body coil electric field distribution on receive-only surface coil heating.

Although in the design of transmit RF coils, B(1) homogeneity is crucial for good image quality, discussion of electric field (E-field) distribution in the literature has been mostly limited to specific absorption rate (SAR) and patient loading (dielectric) effects. In this work, we report on a different aspect of E-field: the receive-only surface coil heating resulting from the voltage drop across the blocking (decoupling) networks and cable traps that are used to minimize the transmit field distortion. The results show that the z-component (parallel to the coil cable) of the E-field has a significant effect on the temperature rise in the surface coil. Therefore, in the receive-only coil designs, it is not sufficient to consider only the induced voltage on the coil loop due to the B(1) field, as is generally done in blocking network analysis calculations. The body coil E-field distribution must be considered as well.

Electricity↗
PubMed2026

Doublesex gene influences sex differentiation and embryonic development in predatory mite Phytoseiulus persimilis.

BACKGROUND: Phytoseiulus persimilis is an effective biocontrol agent characterized by paternal genome elimination (PGE), an unusual reproductive system in which males eliminate the paternal genome during embryogenesis. However, the molecular mechanism underlying sex determination and reproductive regulation in this species remain poorly understood. RESULTS: Transcriptome-based analyses identified two doublesex (dsx) homologs, Ppdsx1 and Ppdsx2, as candidate regulators of reproduction. Weighted gene co-expression network analysis (WGCNA) assigned Ppdsx2 to a pre-mating-associated co-expression module enriched for reproductive and signaling pathways. Functional analyses revealed clear divergence between the two genes. RNA interference (RNAi) of Ppdsx1 reduced the proportion of female offspring, whereas RNAi of Ppdsx2 induced sex reversal, developmental abnormalities, and impaired egg viability. Yeast two-hybrid and glutathione S-transferase (GST) pull-down assays further demonstrated interactions between Dsx proteins and vitellogenin (Vg)-derived fragments identified from a complementary DNA (cDNA) library screen, suggesting a previously unrecognized connection between sex determination and reproductive nutrient allocation. CONCLUSIONS: Ppdsx1 contributes to maintenance of the female developmental pathway, whereas Ppdsx2 represents a strong candidate component of the PGE-associated sex-determination cascade. The observed Dsx-Vg fragment interaction suggests a potential link between reproductive developmental programs and nutrient allocation pathways. These findings provide new insights into the molecular basis of sex determination and reproductive regulation in phytoseiid mites and establish a foundation for future studies on the coupling of reproductive development and resource allocation. © 2026 Society of Chemical Industry.

Animals↗
PubMed2001

Identification and characterization of Saccharomyces cerevisiae mutants defective in fluid-phase endocytosis.

A mutant library generated by the European Functional Analysis Network (EUROFAN) was screened for strains defective in fluid-phase endocytosis. Accumulation of Lucifer yellow in the vacuole was used as a marker for efficient endocytosis. Fourteen mutants, including ede1Delta, rcy1Delta, sys1Delta and tlg2Delta, previously described to be involved in membrane trafficking, were identified in this screen. alpha-Factor uptake, endocytosis of FM4-64, carboxypeptidase Y secretion, vacuolar morphology, and a vma2 synthetic growth defect were used as criteria to characterize the endocytic defect of the mutant strains obtained. Accordingly, eight mutant strains have endocytic phenotypes in addition to their defect in Lucifer yellow accumulation. These fluid-phase endocytosis mutants are defective at different steps of the endocytic pathway. Interestingly, only two mutants were defective for internalization, two for vacuolar protein sorting and four mutants had aberrant vacuolar morphologies. Some of the mutants identified in this screen that sort carboxypeptidase Y correctly may affect endocytosis at an early post-internalization step before the intersection of the endocytic with the vacuolar protein-sorting pathway.

Carboxypeptidases↗
PubMed2002

Mutants defective in secretory/vacuolar pathways in the EUROFAN collection of yeast disruptants.

We have screened the EUROFAN (European Functional Analysis Network) deletion strain collection for yeast mutants defective in secretory/vacuolar pathways and/or associated biochemical modifications. We used systematic Western immunoblotting to analyse the electrophoretic pattern of several markers of the secretory/vacuolar pathways, the soluble alpha-factor, the periplasmic glycoprotein invertase, the plasma membrane GPI-anchored protein Gas1p, and two vacuolar proteins, the soluble carboxypeptidase Y and the membrane-bound alkaline phosphatase, which are targeted to the vacuole by different pathways. We also used colony immunoblotting to monitor the secretion of carboxypeptidase Y into the medium, to identify disruptants impaired in vacuolar targeting. We identified 25 mutants among the 631 deletion strains. Nine of these mutants were disrupted in genes identified in recent years on the basis of their involvement in trafficking (VPS53, VAC7, VAM6, APM3, SYS1), or glycosylation (ALG12, ALG9, OST4, ROT2). Three of these genes were identified on the basis of trafficking defects by ourselves and others within the EUROFAN project (TLG2, RCY1, MON2). The deletion of ERV29, which encodes a COPII vesicle protein, impaired carboxypeptidase Y trafficking from the endoplasmic reticulum to the Golgi apparatus. We also identified eight unknown ORFs, the deletion of which reduced Golgi glycosylation or impaired the Golgi to vacuole trafficking of carboxypeptidase Y. YJR044c, which we identified as a new VPS gene, encodes a protein with numerous homologues of unknown function in sequence databases.

Alkaline Phosphatase↗
PubMed2000

Nonlinear Trends in Hippocampal Metabolic Function and Verbal Memory: Evidence of Cognitive Reserve in Temporal Lobe Epilepsy?

The present study explored the possibility of nonlinear trends in the relationship between verbal memory and hippocampal function in a series of 33 patients with temporal lobe epilepsy (TLE). Right and left hippocampal metabolic function was quantified using levels of hippocampal creatine to N-acetylaspartate (Cr/NAA) derived from (1)H magnetic resonance spectroscopic imaging. An exploratory neural network analysis (multi-layer perceptron) suggested the possibility of either a quadratic or cubic trend in the relationship between left hippocampal Cr/NAA and verbal retention. Using regression-based curve estimation, the cubic function was found to optimally fit the data, explaining 41% of the variance in the relationship between verbal memory and hippocampal metabolic function. This was contrasted to the 28% variance explained by simple linear regression. These findings suggest that (1) the relationship between verbal retention and hippocampal function in patients with TLE is nonlinear, and (2) this could be explained in terms of a possible "cognitive reserve." Clinical implications are discussed.

Journal Article↗
PubMedDate not supplied

The structure and function of the Niemann-Pick C1 protein.

Niemann-Pick C (NPC) disease is a recessive cholesterol storage disorder characterized by severe, progressive neurodegeneration. The primary causative gene found on chromosome 18q11-12 was identified by a positional cloning approach. The NPC1 gene product is predicted to be a large polytopic glycoprotein with a cytoplasmic tail containing a dileucine endosome-targeting motif. The NPC1 protein sequence shares strong homology with a newly identified homologue, NPC1L1, and the morphogen receptor Patched. In addition, a group of five NPC1 transmembrane domains share homology with the sterol-sensing domain of proteins involved in cellular cholesterol homeostasis. Subcellular localization studies have shown NPC1 to reside in late endosomes and to transiently associate with lysosomes and the trans-Golgi network. Analysis of its topological arrangement in membranes suggests that NPC1 contains 13 transmembrane domains and three large, hydrophilic, lumenal loops. Currently, there is no direct evidence as to the function of the NPC1 protein; however, a number of observations suggest that NPC1 may be related to a family of prokaryotic efflux pumps and thus it may also act as a molecular pump.

Amino Acid Sequence↗
PubMed1996

Imaging motor-to-sensory discharges in the human brain: an experimental tool for the assessment of functional connectivity.

We present a new approach to studying functional connectivity in the human brain. This approach is based on the observation that when we engage in motor activity, a discharge corollary to the motor command is sent from motor to sensory structures. Thus, as long as movement-related sensory input is either prevented or masked, modulation of neuronal activity in sensory structures would indicate the presence of functional connectivity between the motor and the sensory regions. Using positron emission tomography, such a central interaction between motor and sensory regions can be assessed by measuring regional changes in cerebral blood flow (CBF) in sensory regions. In this paper, we describe the experimental design and the results of two studies of corollary discharges, namely those generated during eye movements and speech. In these studies, a graded approach was used to establish the relationship between the number of eye movements or utterances and CBF in visual or auditory regions, respectively. Significant covariations between the number of movements and CBF in sensory regions were found, thus indicating the presence of functional connectivity between motor and sensory regions. In addition, interregional CBF covariations were computed and the effect of removing the intersubject variance on these covariations was evaluated. The corollary-discharge-based approach to studying functional connectivity is discussed in the context of more traditional computational approaches to network analysis in functional brain imaging.

Brain↗
PubMed2002

Effective connectivity and intersubject variability: using a multisubject network to test differences and commonalities.

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m x n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or "input" region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Adult↗
PubMed1994

Oscillations and multiple steady states in active membrane transport models.

The dynamic behavior of some non-linear extensions of the six-state alternating access model for active membrane transport is investigated. We use stoichio-metric network analysis to study the stability of steady states. The bifurcation analysis has been done through standard numerical methods. For the usual six-state model we have proved that there is only one steady state, which is globally asymptotically stable. When we added an autocatalytic step we found self-oscillations. For the competition between a monomer cycle and a dimer cycle, with steps of dimer formation, we have also found self-oscillations. We have also studied models involving the formation of a complex with other molecules. The addition of two steps for formation of a complex of the monomer with another molecule does not alter either the number or the stability of steady states of the basic six-state model. The model which combines the formation of a complex with an autocatalytic step shows both self-oscillations and multiple steady states. The results lead us to conclude that oscillations could be produced by active membrane transport systems if the transport cycle contains a sufficiently large number of steps (six in the present case) and is coupled to at least one autocatalytic reaction,. Oscillations are also predicted when the monomer cycle is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a simplification of the model involving competition between monomer and dimer cycles, which seems to be a more realistic description of biological systems. A self-regulation mechanism of the pumps, related to the multiple stationary states, is expected only for a combined effect of autocatalysis and formation of complexes with other molecules. Within the six-state model this model also leads to oscillation.

Biological Transport, Active↗
PubMed1992

Respiratory network remains functional in a mature guinea pig brainstem isolated in vitro.

We previously developed a perfused isolated brainstem preparation in the adult guinea pig (Morin-Surun and Denavit-Saubie 1989a) which permitted us to describe several types of rhythmic neuronal discharge. In the present study, we demonstrate that nearly all the periodic neuronal activity we recorded in the ventral respiratory areas were directly related to the respiratory-like periodic output of the hypoglossal nerve. This respiratory-like activity lasted several hours only when the brainstem was perfused by the basilar artery. This shows the necessity of the intraarterial perfusion to preserve a functional respiratory network. Analysis of the characteristics of hypoglossal respiratory-like activity shows that (1) two types of respiratory rhythms can be recorded; one with long respiratory phases (inspiratory and expiratory) and one with short respiratory phases. Depending on the preparation, either type occurs alone or intermingled with the other. (2) The shape of the inspiratory-like activity can change throughout the recording period while the periodicity remains stable. This preparation generates a respiratory rhythm and enables us to dissociate the different mechanisms involved in respiratory neurogenesis.

Animals↗
PubMed1979

The primary group as supportive milieu: applications to community psychology.

The paper reviews evidence documenting the health-protective effects of the informal social support extended by kith, kin, and community gatekeepers. Noteworthy features of a classification scheme describing the substance of informal helping behaviors are reviewed. Implications for future research and action address: (a) the need for professionals to reexamine occasions for the provision of consultation and crisis-intervention services; (b) the potential for using social network analysis to identify vulnerable groups in the community; (c) the merits of advocating on behalf of informal support systems as favorable settings for the accomplishment of primary prevention.

Adaptation, Psychological↗
PubMed1986

Social networks and social competence: exploring the effects of early adolescent friendships.

This study explored the relationship between friendship social network variables and social competence indices using a sample of 98 young black lower SES adolescents. Analyses indicated that perceived emotional support received from friends and the number of reciprocated best friends in an adolescents' social network were related positively. Multivariate hierarchical regression analyses indicated that perceived friend emotional support and number of reciprocated best friends contributed independently to school competence, peer competence, and perceived self-competence measures. The friendship network's school achievement orientation was related positively to school competence but was unrelated to peer or perceived self-competence. Friendship network density did not add to the variance explained by the other network variables. Methodological contributions of this study include the development of a computer program to map friendship networks and the expansion of network analysis beyond the examination of social support functions.

Achievement↗
PubMed1994

Modulation of synaptic events by heavy metals in the central nervous system of mollusks.

1. The effects of heavy metals (Pb2+, Hg2+, and Zn2+) on synaptic transmission in the identified neural network of Helix pomatia L. and Lymnaea stagnalis L. (Gastropoda, Mollusca) were studied, with investigation of effects on inputs and outputs as well as on interneuronal connections. 2. The sensory input running from the cardiorenal system to the central nervous system and the synaptic connections between central neurons were affected by heavy metals. 3. Lead and mercury (10(-5)-10(-3) M) eliminated first the inhibitory, then the excitatory inputs running from the heart to central neurons. At the onset of action lead increased the amplitude of the excitatory postsynaptic potentials, but blockade of sensory information transfer occurred after 10-20 min of treatment. 4. The monosynaptic connections between identified interneurons were inhibited by lead and mercury but not by zinc. Motoneurons were found to be less sensitive to heavy metal treatment than interneurons or sensory pathways. 5. The treatment with Pb2+ and Hg2+ often elicited pacemaker and bursting-type firing in central neurons, accompanied by disconnection of synaptic pathways, manifested by insensitivity to sensory synaptic influences. 6. Zn2+ treatment also sometimes induced pacemaker activity and burst firing but did not cause disconnection of the synaptic transmission between interneurons. 7. A network analysis of heavy metal effects can be a useful tool in understanding the connection between their cellular and their behavioral modulatory influences.

Animals↗
PubMed1996

Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes.

Polymorphism of the ABO blood group gene was investigated in 262 healthy Japanese donors by a polymerase chain reactions-single-strand conformation polymorphism (PCR-SSCP) method, and 13 different alleles were identified. The number of alleles identified in each group was 4 for A1 (provisionally called ABO*A101, *A102, *A103 and *A104 according to the guidelines for human gene nomenclature), 3 for B (ABO*B101, *B102 and *B103), and 6 for O (ABO*O101, *O102, *O103, *O201, *O202 and *O203). Nucleotide sequences of the amplified fragments with different SSCP patterns were determined by direct sequencing. Phylogenetic network analysis revealed that these alleles could be classified into three major lineages, *A/*O1, *B and *O2. In Japanese, *A102 and *B101 were the predominant alleles with frequencies of 83% and 97% in each group, respectively, whereas in group O, two common alleles, *O101 (43%) and *O201 (53%), were observed. These results may be useful for the establishment of ABO genotyping, and these newly described ABO alleles would be advantageous indicators for population studies.

ABO Blood-Group System↗