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PubMed1994

Mapping a social network of heterosexuals at high risk for HIV infection.

OBJECTIVE: To determine how heterosexuals at risk for HIV infection interconnect in social networks and how such relationships affect HIV transmission. DESIGN: Cross-sectional study with face-to-face interviews to ascertain sociosexual connections; serologic testing. PARTICIPANTS: Prostitute women (n = 133), their paying (n = 129) and non-paying (n = 47) male partners; injecting drug users (n = 200) and their sex partners (n = 41). Participants were recruited in sexually transmitted disease and methadone clinics, an HIV-testing site, and through street outreach in Colorado Springs, Colorado, USA. MAIN OUTCOME MEASURES: Reported behaviors, risk perceptions, sociosexual linkages, and HIV prevalence. RESULTS: Respondents were well informed, but reported engaging in high-risk behaviors frequently. Nevertheless, over 70% of respondents perceived themselves to be at low risk for HIV infection. The 595 respondents identified a social network of 5162 people to which they belonged. Network analytic methods indicated 147 separate connected components of this network; eight of the 19 HIV-positive individuals in the network were located in smaller components remote from the largest connected component. CONCLUSION: The isolated position of HIV-positive individuals may serve as a barrier to HIV transmission and may account for the lack of diffusion of HIV in heterosexual populations in this region. Network analysis appears useful for understanding the dynamics of disease transmission and warrants further development as a tool for intervention and control.

Adult↗
PubMed1997

A theoretical model of cerebral hemodynamics: application to the study of arteriovenous malformations.

A comprehensive computer model of the cerebral circulation, based on both hydrodynamics and electrical network analysis, was used to investigate the influences of arteriovenous malformations (AVM) on regional cerebral hemodynamics. The basic model contained 114 normal compartments: 55 arteries, 37 veins, 20 microvessel groups (MVG), one compartment representing systemic and extracranial vascular resistance, and one representing the heart. Each microvessel group, which represented the arteriolar bed, consisted of 5000 microvessels. Cerebral blood flow autoregulation was simulated by a formula that determined the resistance and therefore the flow rate of the microvessel groups (arterioles) as a function of perfusion pressure. Elasticity was introduced to describe the compliance of each vessel. Flow rate was made a controlling factor for the positive regulation of the diameters of conductance vessels by calculation of shear stress on the vessel wall (vessel dilation). Models containing an AVM were constructed by adding an AVM compartment and its feeding arteries and draining veins. In addition to the basic model, AVM models were simulated with and without autoregulation and flow-induced conductance vessel dilation to evaluate the contributions of these factors on cerebral hemodynamics. Results for the model with vessel dilation were more similar to clinical observations than those without vessel dilation. Even in the presence of total vasoparalysis of the arteriolar bed equivalent, obliteration of a large (1000 mL/min) shunt flow AVM resulted in a near-field CBF increase from a baseline of 21 to a post-occlusion value of no more than 74 mL/100 g/min, casting doubt on a purely hemodynamic basis for severe hyperemia after treatment. The results of the simulations suggest that our model may be a useful tool to study hemodynamic problems of the cerebral circulation.

Animals↗
PubMed1988

Social networks, social support, and elderly institutionalized people.

This article shows how social network studies contribute to development of knowledge about social support and describes research on the social networks of elderly institutionalized people. Network patterns emerged from data obtained through an anthropological fieldwork approach to network analysis. They are discussed in connection with a conceptualization of support as esteem enhancement and coping assistance. Residents' points of view are reported in their own words as much as possible to preserve active images that confront stereotypes of elderly people as passive and dependent. Their responses illustrate important aspects of social support in institutional settings that have implications for scientific nursing practice.

Aged↗
PubMed2003

Individual, contextual, and social network factors affecting exposure to HIV/AIDS risk among older residents living in low-income senior housing complexes.

This study examines the influence of individual, contextual (building location and characteristics), and social network characteristics on HIV prevalence and risk behavior among people older than 50 years of age living in low-income senior housing in two cities, Hartford, Connecticut and Chicago, Illinois. The authors' study focuses on older residents of six buildings located in impoverished neighborhoods with high rates of HIV transmission through injection drug use and unprotected sexual activity, including the exchange of sex for drugs and money. The article is organized into three sections. First, the authors explore the HIV prevalence, distribution, and risk behaviors that may contribute to new infections among the buildings' older residents in general. These practices include unprotected sexual intercourse, sex with commercial sex workers, casual or multiple partners, regular use of alcohol and/or illicit drugs, and other high-risk activities that expose older residents to HIV, sexually transmitted diseases, and other negative health consequences. Next, the authors examine the relationship between building and neighborhood characteristics, the internal social organization of buildings, and the risk behaviors of individual residents by building residency. Finally, the authors use a social network analysis to identify possible entry points and transmission routes for HIV infection through drug and sexual exchanges between and among building residents and visitors. This approach also reveals variations in building structures that may facilitate the diffusion of HIV prevention efforts.

Acquired Immunodeficiency Syndrome↗
PubMed2024

DGKH-mediated phosphatidic acid oncometabolism as a driver of self-renewal and therapy resistance in HCC.

BACKGROUND AND AIMS: HCC is characterized by metabolic pathway aberrations, which enable cancer cells to meet their energy demands and accelerate malignant progression. Identifying novel metabolic players governing therapy resistance and self-renewal in HCC is crucial, as these properties are likely responsible for tumor recurrence. APPROACH AND RESULTS: Clinical traits and RNA-seq of patients with HCC in The Cancer Genome Atlas were used for weighted gene coexpression network analysis, where 1 module was significantly correlated with advanced pathological stage and stem cell population maintenance. Further analysis of this module by integrating data obtained from HCC patient nonresponders to tyrosine kinase inhibitors identified 361 commonly deregulated genes. Intriguingly, these genes are significantly enriched in the intracellular signal transduction pathway, with diacylglycerol kinase eta (DGKH) ranked as the most enriched gene in poorly differentiated HCC tumors. Clinically, DGKH was elevated in tumor tissues compared to nontumor tissues. Patients with higher DGKH expression exhibited a more undifferentiated state and were less responsive to tyrosine kinase inhibitors. Functional assays using DGKH-manipulated HCC cell lines demonstrated that DGKH augmented aggressive features, including cancer stemness, therapy resistance, and metastasis. Upstream of DGKH , we discovered that the E1A-associated protein p300 (EP300) binds to DGKH's promoter region, thereby increasing its transcriptomic expression. Mechanistically, DGKH promotes mTOR signaling by producing phosphatidic acid. In an immunocompetent mouse model, cotreatment with sorafenib and liver-directed AAV8-mediated Dgkh depletion significantly reduced tumor burden, self-renewal, phosphatidic acid production, and mTOR signaling. CONCLUSIONS: Our research demonstrated that DGKH is a crucial oncometabolic regulator of cancer stemness and therapy resistance, suggesting that inhibiting DGKH may lead to more effective HCC treatment.

Humans↗
PubMed2025

Inflammatory pathways and immune dysregulation in pediatric postoperative septic shock: A study integrating transcriptomics, machine learning and molecular docking.

This study elucidates the molecular and immune regulatory mechanisms of pediatric postoperative septic shock. Transcriptomic data were obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using the limma package, and gene co-expression modules were constructed using Weighted Gene Co-expression Network Analysis. Functional enrichment was performed via gene set enrichment analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Immune cell infiltration was assessed using ESTIMATE and CIBERSORT. Mendelian randomization was applied to explore causal relationships between gene expression and septic shock. Feature genes were selected using machine learning algorithms, and a diagnostic nomogram model was constructed. Finally, molecular docking analysis was performed to screen and evaluate the binding affinity of traditional Chinese medicine monomers to core target proteins. A total of 1331 differentially expressed genes were identified, and the turquoise module was strongly correlated with septic shock. Enrichment analysis revealed significant activation of IL-6/JAK/STAT3, TNF-α/NF-κB, and PI3K/Akt/mTOR pathways. Immune infiltration analysis indicated suppressed immune scores and imbalances in neutrophils, macrophages, T cells, and B cells. Mendelian randomization confirmed causal associations for 6 genes, including PIM3. The predictive model based on feature genes demonstrated high diagnostic performance. Molecular docking suggested that quercetin and astramembrannin I could stably bind PIM3. This study systematically identified core genes, dysregulated immune pathways, and candidate small-molecule interventions in pediatric septic shock, providing novel insights for early diagnosis and targeted therapy.

Humans↗
PubMed2026

TCGA-based identification of prognostic biomarkers and candidate traditional Chinese medicine compounds in papillary thyroid carcinoma: An observational study.

This study aimed to identify prognostic genes associated with papillary thyroid carcinoma (PTC) and explore candidate traditional Chinese medicine (TCM) compounds using integrated bioinformatics and molecular docking. In this observational study, PTC gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. Differentially expressed genes were screened using differential-expression sequencing (DESeq2), followed by protein-protein interaction network analysis to identify hub genes. Their expression, diagnostic value, immune relevance, prognostic significance, protein-level validation, and single-cell distribution were assessed using gene expression profiling interactive analysis, receiver operating characteristic analysis, immune infiltration analysis, Kaplan-Meier survival analysis, the human protein atlas, and single-cell RNA-sequencing data. Candidate TCM compounds were predicted using symptom mapping (SymMap) and the TCM Systems Pharmacology Database and Analysis Platform, and molecular docking was performed to evaluate potential ligand-target interactions. Five hub genes, colony-stimulating factor 2, apolipoprotein E, fibronectin 1 (FN1), collagen type I alpha 1 chain (COL1A1), and intercellular adhesion molecule 1, were identified and found to be significantly upregulated in PTC tissues, with diagnostic value in receiver operating characteristic analysis. Immune infiltration analysis showed associations with macrophages, dendritic cells, and T helper 1 cells, whereas single-cell analysis demonstrated heterogeneous expression across immune and stromal cell populations, including fibroblasts. Higher FN1 and COL1A1 expression was associated with poorer outcomes. Immunohistochemistry supported the expression patterns, while single-cell analysis provided exploratory cell-type-level context for the cellular distribution of selected genes. Ginseng and Smilax glabra were predicted as common candidate TCMs, and docking suggested favorable binding between their active compounds and selected hub targets. Colony-stimulating factor 2, apolipoprotein E, FN1, COL1A1, and intercellular adhesion molecule 1 may be biologically relevant hub genes in PTC, while FN1 and COL1A1 may have prognostic value. Predicted TCM compounds provide preliminary computational evidence for possible compound-target interactions, requiring experimental and clinical validation.

Female↗
PubMed1996

Ancient DNA suggests a recent expansion of European cattle from a diverse wild progenitor species.

A total of 11 Bos primigenius and Bos taurus bones from archaeological sites between 500 and 12000 years old were examined for the presence of DNA. It was possible to amplify and sequence mitochondrial control region DNA extracted from seven of the 11 samples, including two Pleistocene B. primigenius samples. We compared the results with published data by constructing phylogenetic networks. The two B. primigenius samples clustered with the extant B. taurus samples in the networks. The similarity between B. primigenius and modern taurine cattle confirms that these should be considered members of a single species. The sequences obtained from the B. taurus specimens were either identical to the reference sequence for modern European cattle or closely related to it. They included two sequences not previously documented. The network analysis of the ancient data highlights the intermediary nature of the B. primigenius sequences between modern European and African B. taurus and the proximity of the ancient DNA B. taurus sequences to modern European B. taurus. Further analysis of the extant data in the light of the ancient DNA results suggests that a degree of Pleistocene diversity survives in the extant European Bos population that is mainly derived from a more recent population expansion.

Animals↗
PubMed2006

Mitochondrial diversity in European and Chinese pigs is consistent with population expansions that occurred prior to domestication.

Mitochondrial DNA (mtDNA) diversity in European and Asian pigs was assessed using 1536 samples representing 45 European and 21 Chinese breeds. Diagnostic nucleotide differences in the cytochrome b (Cytb) gene between the European and Asian mtDNA variants were determined by pyrosequencing as a rapid screening method. Subsequently, 637bp of the hypervariable control region was sequenced to further characterize mtDNA diversity. All sequences belonged to the D1 and D2 clusters of pig mtDNA originating from ancestral wild boar populations in Europe and Asia, respectively. The average frequency of Asian mtDNA haplotypes was 29% across European breeds, but varied from 0 to 100% within individual breeds. A neighbour-joining (NJ) tree of control region sequences showed that European and Asian haplotypes form distinct clusters consistent with the independent domestication of pigs in Asia and Europe. The Asian haplotypes found in the European pigs were identical or closely related to those found in domestic pigs from Southeast China. The star-like pattern detected by network analysis for both the European and Asian haplotypes was consistent with a previous demographic expansion. Mismatch analysis supported this notion and suggested that the expansion was initiated before domestication.

Animals↗
PubMed2006

Darwin at the molecular scale: selection and variance in electron tunnelling proteins including cytochrome c oxidase.

Biological electron transfer is designed to connect catalytic clusters by chains of redox cofactors. A review of the characterized natural redox proteins with a critical eye for molecular scale measurement of variation and selection related to physiological function shows no statistically significant differences in the protein medium lying between cofactors engaged in physiologically beneficial or detrimental electron transfer. Instead, control of electron tunnelling over long distances relies overwhelmingly on less than 14 A spacing between the cofactors in a chain. Near catalytic clusters, shorter distances (commonly less than 7 A) appear to be selected to generate tunnelling frequencies sufficiently high to scale the barriers of multi-electron, bond-forming/-breaking catalysis at physiological rates. We illustrate this behaviour in a tunnelling network analysis of cytochrome c oxidase. In order to surmount the large, thermally activated, adiabatic barriers in the 5-10 kcal mol-1 range expected for H+ motion and O2 reduction at the binuclear centre of oxidase on the 10(3)-10(5) s-1 time-scale of respiration, electron access with a tunnelling frequency of 10(9) or 10(10) s-1 is required. This is provided by selecting closely placed redox centres, such as haem a (6.9 A) or tyrosine (4.9 A). A corollary is that more distantly placed redox centres, such as CuA, cannot rapidly scale the catalytic site barrier, but must send their electrons through more closely placed centres, avoiding direct short circuits that might circumvent proton pumping coupled to haems a to a3 electron transfer. The selection of distances and energetic barriers directs electron transfer from CuA to haem a rather than a3, without any need for delicate engineering of the protein medium to 'hard wire' electron transfer. Indeed, an examination of a large number of oxidoreductases provides no evidence of such naturally selected wiring of electron tunnelling pathways.

Catalysis↗
PubMed2006

Systematic identification of functional orthologs based on protein network comparison.

Annotating protein function across species is an important task that is often complicated by the presence of large paralogous gene families. Here, we report a novel strategy for identifying functionally related proteins that supplements sequence-based comparisons with information on conserved protein-protein interactions. First, the protein interaction networks of two species are aligned by assigning proteins to sequence homology clusters using the Inparanoid algorithm. Next, probabilistic inference is performed on the aligned networks to identify pairs of proteins, one from each species, that are likely to retain the same function based on conservation of their interacting partners. Applying this method to Drosophila melanogaster and Saccharomyces cerevisiae, we analyze 121 cases for which functional orthology assignment is ambiguous when sequence similarity is used alone. In 61 of these cases, the network supports a different protein pair than that favored by sequence comparisons. These results suggest that network analysis can be used to provide a key source of information for refining sequence-based homology searches.

Animals↗
PubMed2005

Detecting a currency's dominance or dependence using foreign exchange network trees.

In a system containing a large number of interacting stochastic processes, there will typically be many nonzero correlation coefficients. This makes it difficult to either visualize the system's interdependencies, or identify its dominant elements. Such a situation arises in foreign exchange (FX), which is the world's biggest market. Here we develop a network analysis of these correlations using minimum spanning trees (MSTs). We show that not only do the MSTs provide a meaningful representation of the global FX dynamics, but they also enable one to determine momentarily dominant and dependent currencies. We find that information about a country's geographical ties emerges from the raw exchange-rate data. Most importantly from a trading perspective, we discuss how to infer which currencies are "in play" during a particular period of time.

Journal Article↗
PubMed2006

Identification of key residues in proteins by using their physical characters.

Key residues in proteins are important to their stability, folding, and functions. They usually are highly conserved and can be identified by sequence or structure alignments. However, these methods can only determine the locations of key residues in sequences and structures and give less information about their physical characters. In this paper, we try to identify key residues by analyzing their inter-residue interactions. The model we study is the protein domain from transducin. We show that the usual Gaussian network analysis and distance-based contact analysis have difficulty identifying the key residues in this protein, but the contact energies can do it well. We find that most key residues can be located by the lowest contact energies. This enables us to predict and analyze the key residues in other proteins. Our results suggest that contact energy analysis may provide an alternative approach to investigating the folding and stability of proteins.

Amino Acid Sequence↗
PubMed1993

Modeling the neuron-microtransducer junction: from extracellular to patch recording.

This paper is devoted to a detailed characterization of the neuron-to-microtransducer junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with the general-purpose network-analysis program SPICE. Both noble-metal microelectrodes and insulated-gate FET's are considered. The responses of such devices are characterized as functions of several parameters, e.g., sealing impedance, density of ionic currents in the cell membrane, and spatial discontinuities of the adhesion process. It is shown that the various signal shapes reported in the literature can be reproduced and interpreted in terms of time derivatives of the action potential. In this way, the shape of any experimental signal can be interpreted on the basis of a specific sealing condition. Possible future improvements in microtransducer design, based on the proposed approach, are also suggested.

Action Potentials↗
PubMed2001

Equivalent network representation for thickness vibration modes in piezoelectric plates with a linearly graded parameter.

Equivalent network representation is derived for thickness vibration modes in piezoelectric plates with a linearly graded parameter. The network is composed of a transmission line of a finite length, which is linked to the electric excitation port via ideal transformers connected serially at both ends. The ratios of the two transformers are different from each other and frequency dependent. Two frequency-dependent capacitors of the same value but opposite sign appear at the electric port. The frequency characteristic of the input electric admittance of the resonator, which shows the unique feature of the graded piezoelectric plate, is demonstrated by the equivalent network analysis.

Letter↗
PubMedDate not supplied

The peer group as a context for the development of young adolescent motivation and achievement.

This study investigated the peer group as a context for the socialization of young adolescents' motivation and achievement in school. Social network analysis was used to identify peer groups of adolescents in middle school whose members regularly interacted with each other (N = 331). Actual reports from these peer group members were used to assess peer group characteristics. Multilevel analyses indicated that peer groups did socialize some academic characteristics, controlling for selection factors. Students' peer group context in the fall predicted changes in their liking and enjoyment of school (intrinsic value) and their achievement over the school year. Students' peer group context was unrelated to changes in their beliefs about the importance of school (utility value) or expectancies for success over the school year.

Adolescent↗
PubMedDate not supplied

Examination of peer-group contextual effects on aggression during early adolescence.

Peer group contextual effects of aggressive behavior among middle school students (6th-8th graders) were examined using a short-term longitudinal design. More specifically, the homophily hypothesis that peer group membership influences individual-level bullying and fighting was evaluated with multilevel sex-specific models of individual- and peer-level aggression scores. Peer groups were identified via social network analysis. Intraclass correlation coefficients yielded through hierarchical linear modeling demonstrated substantial within-group similarity on self-reported bullying and fighting, suggesting that students affiliate with individuals who bully and fight at the same frequency. Peer group bullying and fighting was associated with individual-level behavior, even after controlling individual baseline levels for males and females. However, peer contextual effects explained more variance in individual bullying than individual fighting. This differential impact of peer group membership suggests that future studies consider peer relations across subtypes of aggression.

Adolescent↗
PubMed1996

Multiparametric image cytometry in mycosis fungoides.

Eighteen cases of early mycosis fungoides were compared with 18 cases of eczematous dermatitis by multiparametric image cytometry. A minimum of 100 lymphocytes was measured in each case. A large number of measurements was acquired for each lymphocyte, characterizing nuclear DNA content, area, shape, and texture. There were significant differences between the two groups, especially in nuclear DNA content and texture. These differences allowed the two groups of nuclei to be distinguished with 78% accuracy. The two groups of lesions were distinguished with 94% accuracy, using neural network analysis.

Cell Nucleus↗