Detection of Protein Complexes Based on Penalized Matrix Decomposition in a Sparse Protein⁻Protein Interaction Network.

PubMed

Cao, Buwen; Deng, Shuguang; Qin, Hua; Ding, Pingjian; Chen, Shaopeng; Li, Guanghui

2018-06-15

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease rapidly when applied to sparse protein⁻protein interaction (PPI) networks. In this study, based on penalized matrix decomposition ( PMD ), a novel method of penalized matrix decomposition for the identification of protein complexes (i.e., PMD pc ) was developed to detect protein complexes in the human protein interaction network. This method mainly consists of three steps. First, the adjacent matrix of the protein interaction network is normalized. Second, the normalized matrix is decomposed into three factor matrices. The PMD pc method can detect protein complexes in sparse PPI networks by imposing appropriate constraints on factor matrices. Finally, the results of our method are compared with those of other methods in human PPI network. Experimental results show that our method can not only outperform classical algorithms, such as CFinder, ClusterONE, RRW, HC-PIN, and PCE-FR, but can also achieve an ideal overall performance in terms of a composite score consisting of F-measure, accuracy (ACC), and the maximum matching ratio (MMR).

Context-based retrieval of functional modules in protein-protein interaction networks.

PubMed

Dobay, Maria Pamela; Stertz, Silke; Delorenzi, Mauro

2017-03-27

Various techniques have been developed for identifying the most probable interactants of a protein under a given biological context. In this article, we dissect the effects of the choice of the protein-protein interaction network (PPI) and the manipulation of PPI settings on the network neighborhood of the influenza A virus (IAV) network, as well as hits in genome-wide small interfering RNA screen results for IAV host factors. We investigate the potential of context filtering, which uses text mining evidence linked to PPI edges, as a complement to the edge confidence scores typically provided in PPIs for filtering, for obtaining more biologically relevant network neighborhoods. Here, we estimate the maximum performance of context filtering to isolate a Kyoto Encyclopedia of Genes and Genomes (KEGG) network Ki from a union of KEGG networks and its network neighborhood. The work gives insights on the use of human PPIs in network neighborhood approaches for functional inference. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Constructing an integrated gene similarity network for the identification of disease genes.

PubMed

Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin

2017-09-20

Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

PROPER: global protein interaction network alignment through percolation matching.

PubMed

Kazemi, Ehsan; Hassani, Hamed; Grossglauser, Matthias; Pezeshgi Modarres, Hassan

2016-12-12

The alignment of protein-protein interaction (PPI) networks enables us to uncover the relationships between different species, which leads to a deeper understanding of biological systems. Network alignment can be used to transfer biological knowledge between species. Although different PPI-network alignment algorithms were introduced during the last decade, developing an accurate and scalable algorithm that can find alignments with high biological and structural similarities among PPI networks is still challenging. In this paper, we introduce a new global network alignment algorithm for PPI networks called PROPER. Compared to other global network alignment methods, our algorithm shows higher accuracy and speed over real PPI datasets and synthetic networks. We show that the PROPER algorithm can detect large portions of conserved biological pathways between species. Also, using a simple parsimonious evolutionary model, we explain why PROPER performs well based on several different comparison criteria. We highlight that PROPER has high potential in further applications such as detecting biological pathways, finding protein complexes and PPI prediction. The PROPER algorithm is available at http://proper.epfl.ch .

The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.

PubMed

Rohleder, Cathrin; Wiedermann, Dirk; Neumaier, Bernd; Drzezga, Alexander; Timmermann, Lars; Graf, Rudolf; Leweke, F Markus; Endepols, Heike

2016-01-01

Prepulse inhibition (PPI) is a neuropsychological process during which a weak sensory stimulus ("prepulse") attenuates the motor response ("startle reaction") to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: (i) startle mediation, (ii) PPI mediation, and (iii) modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood. We therefore combined [(18)F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET) with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN) active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e., associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing. Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.

A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology.

PubMed

Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Marashi, Sayed-Amir

2017-02-01

Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein-protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein-protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules

PubMed Central

2016-01-01

Long-term (multiple-week or -month) release of small, water-soluble molecules from hydrogels remains a significant pharmaceutical challenge, which is typically overcome at the expense of more-complicated drug carrier designs. Such approaches are payload-specific and include covalent conjugation of drugs to base materials or incorporation of micro- and nanoparticles. As a simpler alternative, here we report a mild and simple method for achieving multiple-month release of small molecules from gel-like polymer networks. Densely cross-linked matrices were prepared through ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), all of which are commonly available commercial molecules. The loading of model small molecules (Fast Green FCF and Rhodamine B dyes) within these polymer networks increases with the payload/network binding strength and with the PAH and payload concentrations used during encapsulation. Once loaded into the PAH/PPi and PAH/TPP ionic networks, only a few percent of the payload is released over multiple months. This extended release is achieved regardless of the payload/network binding strength and likely reflects the small hydrodynamic mesh size within the gel-like matrices. Furthermore, the PAH/TPP networks show promising in vitro cytocompatibility with model cells (human dermal fibroblasts), though slight cytotoxic effects were exhibited by the PAH/PPi networks. Taken together, the above findings suggest that PAH/PPi and (especially) PAH/TPP networks might be attractive materials for the multiple-month delivery of drugs and other active molecules (e.g., fragrances or disinfectants). PMID:26811936

In silico prediction of protein-protein interactions in human macrophages

PubMed Central

2014-01-01

Background Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level. PMID:24636261

Detecting complexes from edge-weighted PPI networks via genes expression analysis.

PubMed

Zhang, Zehua; Song, Jian; Tang, Jijun; Xu, Xinying; Guo, Fei

2018-04-24

Identifying complexes from PPI networks has become a key problem to elucidate protein functions and identify signal and biological processes in a cell. Proteins binding as complexes are important roles of life activity. Accurate determination of complexes in PPI networks is crucial for understanding principles of cellular organization. We propose a novel method to identify complexes on PPI networks, based on different co-expression information. First, we use Markov Cluster Algorithm with an edge-weighting scheme to calculate complexes on PPI networks. Then, we propose some significant features, such as graph information and gene expression analysis, to filter and modify complexes predicted by Markov Cluster Algorithm. To evaluate our method, we test on two experimental yeast PPI networks. On DIP network, our method has Precision and F-Measure values of 0.6004 and 0.5528. On MIPS network, our method has F-Measure and S n values of 0.3774 and 0.3453. Comparing to existing methods, our method improves Precision value by at least 0.1752, F-Measure value by at least 0.0448, S n value by at least 0.0771. Experiments show that our method achieves better results than some state-of-the-art methods for identifying complexes on PPI networks, with the prediction quality improved in terms of evaluation criteria.

Effective comparative analysis of protein-protein interaction networks by measuring the steady-state network flow using a Markov model.

PubMed

Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

2016-10-06

Comparative analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved functional network modules across different species. Such modules typically consist of orthologous proteins with conserved interactions, which can be exploited to computationally predict the modules through network comparison. In this work, we propose a novel probabilistic framework for comparing PPI networks and effectively predicting the correspondence between proteins, represented as network nodes, that belong to conserved functional modules across the given PPI networks. The basic idea is to estimate the steady-state network flow between nodes that belong to different PPI networks based on a Markov random walk model. The random walker is designed to make random moves to adjacent nodes within a PPI network as well as cross-network moves between potential orthologous nodes with high sequence similarity. Based on this Markov random walk model, we estimate the steady-state network flow - or the long-term relative frequency of the transitions that the random walker makes - between nodes in different PPI networks, which can be used as a probabilistic score measuring their potential correspondence. Subsequently, the estimated scores can be used for detecting orthologous proteins in conserved functional modules through network alignment. Through evaluations based on multiple real PPI networks, we demonstrate that the proposed scheme leads to improved alignment results that are biologically more meaningful at reduced computational cost, outperforming the current state-of-the-art algorithms. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/CUFID .

Identification of infection- and defense-related genes via a dynamic host-pathogen interaction network using a Candida albicans-zebrafish infection model.

PubMed

Kuo, Zong-Yu; Chuang, Yung-Jen; Chao, Chun-Cheih; Liu, Fu-Chen; Lan, Chung-Yu; Chen, Bor-Sen

2013-01-01

Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs. Copyright © 2013 S. Karger AG, Basel.

A Method for Predicting Protein Complexes from Dynamic Weighted Protein-Protein Interaction Networks.

PubMed

Liu, Lizhen; Sun, Xiaowu; Song, Wei; Du, Chao

2018-06-01

Predicting protein complexes from protein-protein interaction (PPI) network is of great significance to recognize the structure and function of cells. A protein may interact with different proteins under different time or conditions. Existing approaches only utilize static PPI network data that may lose much temporal biological information. First, this article proposed a novel method that combines gene expression data at different time points with traditional static PPI network to construct different dynamic subnetworks. Second, to further filter out the data noise, the semantic similarity based on gene ontology is regarded as the network weight together with the principal component analysis, which is introduced to deal with the weight computing by three traditional methods. Third, after building a dynamic PPI network, a predicting protein complexes algorithm based on "core-attachment" structural feature is applied to detect complexes from each dynamic subnetworks. Finally, it is revealed from the experimental results that our method proposed in this article performs well on detecting protein complexes from dynamic weighted PPI networks.

Protein complex prediction in large ontology attributed protein-protein interaction networks.

PubMed

Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

2013-01-01

Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

"Master-Slave" Biological Network Alignment

NASA Astrophysics Data System (ADS)

Ferraro, Nicola; Palopoli, Luigi; Panni, Simona; Rombo, Simona E.

Performing global alignment between protein-protein interaction (PPI) networks of different organisms is important to infer knowledge about conservation across species. Known methods that perform this task operate symmetrically, that is to say, they do not assign a distinct role to the input PPI networks. However, in most cases, the input networks are indeed distinguishable on the basis of how well the corresponding organism is biologically well-characterized. For well-characterized organisms the associated PPI network supposedly encode in a sound manner all the information about their proteins and associated interactions, which is far from being the case for not well characterized ones. Here the new idea is developed to devise a method for global alignment of PPI networks that in fact exploit differences in the characterization of organisms at hand. We assume that the PPI network (called Master) of the best characterized is used as a fingerprint to guide the alignment process to the second input network (called Slave), so that generated results preferably retain the structural characteristics of the Master (and using the Slave) network. We tested our method showing that the results it returns are biologically relevant.

Evolutionary model selection and parameter estimation for protein-protein interaction network based on differential evolution algorithm

PubMed Central

Huang, Lei; Liao, Li; Wu, Cathy H.

2016-01-01

Revealing the underlying evolutionary mechanism plays an important role in understanding protein interaction networks in the cell. While many evolutionary models have been proposed, the problem about applying these models to real network data, especially for differentiating which model can better describe evolutionary process for the observed network urgently remains as a challenge. The traditional way is to use a model with presumed parameters to generate a network, and then evaluate the fitness by summary statistics, which however cannot capture the complete network structures information and estimate parameter distribution. In this work we developed a novel method based on Approximate Bayesian Computation and modified Differential Evolution (ABC-DEP) that is capable of conducting model selection and parameter estimation simultaneously and detecting the underlying evolutionary mechanisms more accurately. We tested our method for its power in differentiating models and estimating parameters on the simulated data and found significant improvement in performance benchmark, as compared with a previous method. We further applied our method to real data of protein interaction networks in human and yeast. Our results show Duplication Attachment model as the predominant evolutionary mechanism for human PPI networks and Scale-Free model as the predominant mechanism for yeast PPI networks. PMID:26357273

Unified Alignment of Protein-Protein Interaction Networks.

PubMed

Malod-Dognin, Noël; Ban, Kristina; Pržulj, Nataša

2017-04-19

Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.

Evidence of Probabilistic Behaviour in Protein Interaction Networks

DTIC Science & Technology

2008-01-31

Evidence of degree-weighted connectivity in nine PPI networks. a, Homo sapiens (human); b, Drosophila melanogaster (fruit fly); c-e, Saccharomyces...illustrates maps for the networks of Homo sapiens and Dro- sophila melanogaster, while maps for the remaining net- works are provided in Additional file 2. As...protein-protein interaction networks. a, Homo sapiens ; b, Drosophila melanogaster. Distances shown as average shortest path lengths L(k1, k2) between

Prediction of cassava protein interactome based on interolog method.

PubMed

Thanasomboon, Ratana; Kalapanulak, Saowalak; Netrphan, Supatcharee; Saithong, Treenut

2017-12-08

Cassava is a starchy root crop whose role in food security becomes more significant nowadays. Together with the industrial uses for versatile purposes, demand for cassava starch is continuously growing. However, in-depth study to uncover the mystery of cellular regulation, especially the interaction between proteins, is lacking. To reduce the knowledge gap in protein-protein interaction (PPI), genome-scale PPI network of cassava was constructed using interolog-based method (MePPI-In, available at http://bml.sbi.kmutt.ac.th/ppi ). The network was constructed from the information of seven template plants. The MePPI-In included 90,173 interactions from 7,209 proteins. At least, 39 percent of the total predictions were found with supports from gene/protein expression data, while further co-expression analysis yielded 16 highly promising PPIs. In addition, domain-domain interaction information was employed to increase reliability of the network and guide the search for more groups of promising PPIs. Moreover, the topology and functional content of MePPI-In was similar to the networks of Arabidopsis and rice. The potential contribution of MePPI-In for various applications, such as protein-complex formation and prediction of protein function, was discussed and exemplified. The insights provided by our MePPI-In would hopefully enable us to pursue precise trait improvement in cassava.

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways

PubMed Central

Cappi, C; Brentani, H; Lima, L; Sanders, S J; Zai, G; Diniz, B J; Reis, V N S; Hounie, A G; Conceição do Rosário, M; Mariani, D; Requena, G L; Puga, R; Souza-Duran, F L; Shavitt, R G; Pauls, D L; Miguel, E C; Fernandez, T V

2016-01-01

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions. PMID:27023170

Integration of multiple biological features yields high confidence human protein interactome.

PubMed

Karagoz, Kubra; Sevimoglu, Tuba; Arga, Kazim Yalcin

2016-08-21

The biological function of a protein is usually determined by its physical interaction with other proteins. Protein-protein interactions (PPIs) are identified through various experimental methods and are stored in curated databases. The noisiness of the existing PPI data is evident, and it is essential that a more reliable data is generated. Furthermore, the selection of a set of PPIs at different confidence levels might be necessary for many studies. Although different methodologies were introduced to evaluate the confidence scores for binary interactions, a highly reliable, almost complete PPI network of Homo sapiens is not proposed yet. The quality and coverage of human protein interactome need to be improved to be used in various disciplines, especially in biomedicine. In the present work, we propose an unsupervised statistical approach to assign confidence scores to PPIs of H. sapiens. To achieve this goal PPI data from six different databases were collected and a total of 295,288 non-redundant interactions between 15,950 proteins were acquired. The present scoring system included the context information that was assigned to PPIs derived from eight biological attributes. A high confidence network, which included 147,923 binary interactions between 13,213 proteins, had scores greater than the cutoff value of 0.80, for which sensitivity, specificity, and coverage were 94.5%, 80.9%, and 82.8%, respectively. We compared the present scoring method with others for evaluation. Reducing the noise inherent in experimental PPIs via our scoring scheme increased the accuracy significantly. As it was demonstrated through the assessment of process and cancer subnetworks, this study allows researchers to construct and analyze context-specific networks via valid PPI sets and one can easily achieve subnetworks around proteins of interest at a specified confidence level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Applied Graph-Mining Algorithms to Study Biomolecular Interaction Networks

PubMed Central

2014-01-01

Protein-protein interaction (PPI) networks carry vital information on the organization of molecular interactions in cellular systems. The identification of functionally relevant modules in PPI networks is one of the most important applications of biological network analysis. Computational analysis is becoming an indispensable tool to understand large-scale biomolecular interaction networks. Several types of computational methods have been developed and employed for the analysis of PPI networks. Of these computational methods, graph comparison and module detection are the two most commonly used strategies. This review summarizes current literature on graph kernel and graph alignment methods for graph comparison strategies, as well as module detection approaches including seed-and-extend, hierarchical clustering, optimization-based, probabilistic, and frequent subgraph methods. Herein, we provide a comprehensive review of the major algorithms employed under each theme, including our recently published frequent subgraph method, for detecting functional modules commonly shared across multiple cancer PPI networks. PMID:24800226

A network biology-based approach to evaluating the effect of environmental contaminants on human interactome and diseases.

PubMed

Iida, M; Takemoto, K

2018-09-30

Environmental contaminant exposure can pose significant risks to human health. Therefore, evaluating the impact of this exposure is of great importance; however, it is often difficult because both the molecular mechanism of disease and the mode of action of the contaminants are complex. We used network biology techniques to quantitatively assess the impact of environmental contaminants on the human interactome and diseases with a particular focus on seven major contaminant categories: persistent organic pollutants (POPs), dioxins, polycyclic aromatic hydrocarbons (PAHs), pesticides, perfluorochemicals (PFCs), metals, and pharmaceutical and personal care products (PPCPs). We integrated publicly available data on toxicogenomics, the diseasome, protein-protein interactions (PPIs), and gene essentiality and found that a few contaminants were targeted to many genes, and a few genes were targeted by many contaminants. The contaminant targets were hub proteins in the human PPI network, whereas the target proteins in most categories did not contain abundant essential proteins. Generally, contaminant targets and disease-associated proteins were closely associated with the PPI network, and the closeness of the associations depended on the disease type and chemical category. Network biology techniques were used to identify environmental contaminants with broad effects on the human interactome and contaminant-sensitive biomarkers. Moreover, this method enabled us to quantify the relationship between environmental contaminants and human diseases, which was supported by epidemiological and experimental evidence. These methods and findings have facilitated the elucidation of the complex relationship between environmental exposure and adverse health outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Three-Dimensional Networked Metal-Organic Frameworks with Conductive Polypyrrole Tubes for Flexible Supercapacitors.

PubMed

Xu, Xingtao; Tang, Jing; Qian, Huayu; Hou, Shujin; Bando, Yoshio; Hossain, Md Shahriar A; Pan, Likun; Yamauchi, Yusuke

2017-11-08

Metal-organic frameworks (MOFs) with high porosity and a regular porous structure have emerged as a promising electrode material for supercapacitors, but their poor electrical conductivity limits their utilization efficiency and capacitive performance. To increase the overall electrical conductivity as well as the efficiency of MOF particles, three-dimensional networked MOFs are developed via using preprepared conductive polypyrrole (PPy) tubes as the support for in situ growth of MOF particles. As a result, the highly conductive PPy tubes that run through the MOF particles not only increase the electron transfer between MOF particles and maintain the high effective porosity of the MOFs but also endow the MOFs with flexibility. Promoted by such elaborately designed MOF-PPy networks, the specific capacitance of MOF particles has been increased from 99.2 F g -1 for pristine zeolitic imidazolate framework (ZIF)-67 to 597.6 F g -1 for ZIF-PPy networks, indicating the importance of the design of the ZIF-PPy continuous microstructure. Furthermore, a flexible supercapacitor device based on ZIF-PPy networks shows an outstanding areal capacitance of 225.8 mF cm -2 , which is far above other MOFs-based supercapacitors reported up to date, confirming the significance of in situ synthetic chemistry as well as the importance of hybrid materials on the nanoscale.

HubAlign: an accurate and efficient method for global alignment of protein-protein interaction networks.

PubMed

Hashemifar, Somaye; Xu, Jinbo

2014-09-01

High-throughput experimental techniques have produced a large amount of protein-protein interaction (PPI) data. The study of PPI networks, such as comparative analysis, shall benefit the understanding of life process and diseases at the molecular level. One way of comparative analysis is to align PPI networks to identify conserved or species-specific subnetwork motifs. A few methods have been developed for global PPI network alignment, but it still remains challenging in terms of both accuracy and efficiency. This paper presents a novel global network alignment algorithm, denoted as HubAlign, that makes use of both network topology and sequence homology information, based upon the observation that topologically important proteins in a PPI network usually are much more conserved and thus, more likely to be aligned. HubAlign uses a minimum-degree heuristic algorithm to estimate the topological and functional importance of a protein from the global network topology information. Then HubAlign aligns topologically important proteins first and gradually extends the alignment to the whole network. Extensive tests indicate that HubAlign greatly outperforms several popular methods in terms of both accuracy and efficiency, especially in detecting functionally similar proteins. HubAlign is available freely for non-commercial purposes at http://ttic.uchicago.edu/∼hashemifar/software/HubAlign.zip. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

The Topology of the Growing Human Interactome Data.

PubMed

Janjić, Vuk; Pržulj, Nataša

2014-06-01

We have long moved past the one-gene-one-function concept originally proposed by Beadle and Tatum back in 1941; but the full understanding of genotype-phenotype relations still largely relies on the analysis of static, snapshot-like, interaction data sets. Here, we look at what global patterns can be uncovered if we simply trace back the human interactome network over the last decade of protein-protein interaction (PPI) screening. We take a purely topological approach and find that as the human interactome is getting denser, it is not only gaining in structure (in terms of now being better fit by structured network models than before), but also there are patterns in the way in which it is growing: (a) newly added proteins tend to get linked to existing proteins in the interactome that are not know to interact; and (b) new proteins tend to link to already well connected proteins. Moreover, the alignment between human and yeast interactomes spanning over 40% of yeast's proteins - that are involved in regulation of transcription, RNA splicing and other cellcycle- related processes-suggests the existence of a part of the interactome which remains topologically and functionally unaffected through evolution. Furthermore, we find a small sub-network, specific to the "core" of the human interactome and involved in regulation of transcription and cancer development, whose wiring has not changed within the human interactome over the last 10 years of interacome data acquisition. Finally, we introduce a generalisation of the clustering coefficient of a network as a new measure called the cycle coefficient, and use it to show that PPI networks of human and model organisms are wired in a tight way which forbids the occurrence large cycles.

The topology of the growing human interactome data.

PubMed

Janjić, Vuk; Pržulj, Nataša

2014-06-23

We have long moved past the one-gene–one-function concept originally proposed by Beadle and Tatum back in 1941; but the full understanding of genotype–phenotype relations still largely relies on the analysis of static, snapshot-like, interaction data sets. Here, we look at what global patterns can be uncovered if we simply trace back the human interactome network over the last decade of protein- protein interaction (PPI) screening. We take a purely topological approach and find that as the human interactome is getting denser, it is not only gaining in structure (in terms of now being better fit by structured network models than before), but also there are patterns in the way in which it is growing: (a) newly added proteins tend to get linked to existing proteins in the interactome that are not know to interact; and (b) new proteins tend to link to already well connected proteins. Moreover, the alignment between human and yeast interactomes spanning over 40% of yeast’s proteins — that are involved in regulation of transcription, RNA splicing and other cellcycle-related processes—suggests the existence of a part of the interactome which remains topologically and functionally unaffected through evolution. Furthermore, we find a small sub-network, specific to the “core” of the human interactome and involved in regulation of transcription and cancer development, whose wiring has not changed within the human interactome over the last 10 years of interacome data acquisition. Finally, we introduce a generalisation of the clustering coefficient of a network as a new measure called the cycle coefficient, and use it to show that PPI networks of human and model organisms are wired in a tight way which forbids the occurrence large cycles.

The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategies* | Office of Cancer Genomics

Cancer.gov

As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein–protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes.

Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications.

PubMed

Yang, Sumi; Jang, LindyK; Kim, Semin; Yang, Jongcheol; Yang, Kisuk; Cho, Seung-Woo; Lee, Jae Young

2016-11-01

Electrically conductive biomaterials that can efficiently deliver electrical signals to cells or improve electrical communication among cells have received considerable attention for potential tissue engineering applications. Conductive hydrogels are desirable particularly for neural applications, as they can provide electrical signals and soft microenvironments that can mimic native nerve tissues. In this study, conductive and soft polypyrrole/alginate (PPy/Alg) hydrogels are developed by chemically polymerizing PPy within ionically cross-linked alginate hydrogel networks. The synthesized hydrogels exhibit a Young's modulus of 20-200 kPa. Electrical conductance of the PPy/Alg hydrogels could be enhanced by more than one order of magnitude compared to that of pristine alginate hydrogels. In vitro studies with human bone marrow-derived mesenchymal stem cells (hMSCs) reveal that cell adhesion and growth are promoted on the PPy/Alg hydrogels. Additionally, the PPy/Alg hydrogels support and greatly enhance the expression of neural differentiation markers (i.e., Tuj1 and MAP2) of hMSCs compared to tissue culture plate controls. Subcutaneous implantation of the hydrogels for eight weeks induces mild inflammatory reactions. These soft and conductive hydrogels will serve as a useful platform to study the effects of electrical and mechanical signals on stem cells and/or neural cells and to develop multifunctional neural tissue engineering scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

PubMed

Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

2009-09-01

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

L-GRAAL: Lagrangian graphlet-based network aligner.

PubMed

Malod-Dognin, Noël; Pržulj, Nataša

2015-07-01

Discovering and understanding patterns in networks of protein-protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. A few methods have been proposed for global PPI network alignments, but because of NP-completeness of underlying sub-graph isomorphism problem, producing topologically and biologically accurate alignments remains a challenge. We introduce a novel global network alignment tool, Lagrangian GRAphlet-based ALigner (L-GRAAL), which directly optimizes both the protein and the interaction functional conservations, using a novel alignment search heuristic based on integer programming and Lagrangian relaxation. We compare L-GRAAL with the state-of-the-art network aligners on the largest available PPI networks from BioGRID and observe that L-GRAAL uncovers the largest common sub-graphs between the networks, as measured by edge-correctness and symmetric sub-structures scores, which allow transferring more functional information across networks. We assess the biological quality of the protein mappings using the semantic similarity of their Gene Ontology annotations and observe that L-GRAAL best uncovers functionally conserved proteins. Furthermore, we introduce for the first time a measure of the semantic similarity of the mapped interactions and show that L-GRAAL also uncovers best functionally conserved interactions. In addition, we illustrate on the PPI networks of baker's yeast and human the ability of L-GRAAL to predict new PPIs. Finally, L-GRAAL's results are the first to show that topological information is more important than sequence information for uncovering functionally conserved interactions. L-GRAAL is coded in C++. Software is available at: http://bio-nets.doc.ic.ac.uk/L-GRAAL/. n.malod-dognin@imperial.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Evolution versus "intelligent design": comparing the topology of protein-protein interaction networks to the Internet.

PubMed

Yang, Q; Siganos, G; Faloutsos, M; Lonardi, S

2006-01-01

Recent research efforts have made available genome-wide, high-throughput protein-protein interaction (PPI) maps for several model organisms. This has enabled the systematic analysis of PPI networks, which has become one of the primary challenges for the system biology community. In this study, we attempt to understand better the topological structure of PPI networks by comparing them against man-made communication networks, and more specifically, the Internet. Our comparative study is based on a comprehensive set of graph metrics. Our results exhibit an interesting dichotomy. On the one hand, both networks share several macroscopic properties such as scale-free and small-world properties. On the other hand, the two networks exhibit significant topological differences, such as the cliqueishness of the highest degree nodes. We attribute these differences to the distinct design principles and constraints that both networks are assumed to satisfy. We speculate that the evolutionary constraints that favor the survivability and diversification are behind the building process of PPI networks, whereas the leading force in shaping the Internet topology is a decentralized optimization process geared towards efficient node communication.

Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks.

PubMed

Kim, Inhae; Lee, Heetak; Han, Seong Kyu; Kim, Sanguk

2014-10-01

The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.

Bioinspired Design of Strong, Tough, and Highly Conductive Polyol-Polypyrrole Composites for Flexible Electronics.

PubMed

Gao, Fengxian; Zhang, Ning; Fang, Xiaodong; Ma, Mingming

2017-02-22

Inspired by the dynamic network structure of animal dermis, we have designed and synthesized a series of polyol-polypyrrole (polyol-PPy) composites. Polyols and polypyrrole are cross-linked by hydrogen bonding and electrostatic interactions to form a dynamic network, which helps to dissipate destructive energy. We have found a clear correlation between the mechanical properties of polyol-PPy composites and the polyols structure. Particularly, the PEE-PPy film shows both high strength and flexibility, leading to a remarkable tensile toughness comparable to cocoon silk. The combination of outstanding strength, ductility, and conductivity enables polyol-PPy composites (especially PEE-PPy) as potential electronic materials for making flexible electronics.

Prioritizing chronic obstructive pulmonary disease (COPD) candidate genes in COPD-related networks

PubMed Central

Zhang, Yihua; Li, Wan; Feng, Yuyan; Guo, Shanshan; Zhao, Xilei; Wang, Yahui; He, Yuehan; He, Weiming; Chen, Lina

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a multi-factor disease, which could be caused by many factors, including disturbances of metabolism and protein-protein interactions (PPIs). In this paper, a weighted COPD-related metabolic network and a weighted COPD-related PPI network were constructed base on COPD disease genes and functional information. Candidate genes in these weighted COPD-related networks were prioritized by making use of a gene prioritization method, respectively. Literature review and functional enrichment analysis of the top 100 genes in these two networks suggested the correlation of COPD and these genes. The performance of our gene prioritization method was superior to that of ToppGene and ToppNet for genes from the COPD-related metabolic network or the COPD-related PPI network after assessing using leave-one-out cross-validation, literature validation and functional enrichment analysis. The top-ranked genes prioritized from COPD-related metabolic and PPI networks could promote the better understanding about the molecular mechanism of this disease from different perspectives. The top 100 genes in COPD-related metabolic network or COPD-related PPI network might be potential markers for the diagnosis and treatment of COPD. PMID:29262568

Prioritizing chronic obstructive pulmonary disease (COPD) candidate genes in COPD-related networks.

PubMed

Zhang, Yihua; Li, Wan; Feng, Yuyan; Guo, Shanshan; Zhao, Xilei; Wang, Yahui; He, Yuehan; He, Weiming; Chen, Lina

2017-11-28

Chronic obstructive pulmonary disease (COPD) is a multi-factor disease, which could be caused by many factors, including disturbances of metabolism and protein-protein interactions (PPIs). In this paper, a weighted COPD-related metabolic network and a weighted COPD-related PPI network were constructed base on COPD disease genes and functional information. Candidate genes in these weighted COPD-related networks were prioritized by making use of a gene prioritization method, respectively. Literature review and functional enrichment analysis of the top 100 genes in these two networks suggested the correlation of COPD and these genes. The performance of our gene prioritization method was superior to that of ToppGene and ToppNet for genes from the COPD-related metabolic network or the COPD-related PPI network after assessing using leave-one-out cross-validation, literature validation and functional enrichment analysis. The top-ranked genes prioritized from COPD-related metabolic and PPI networks could promote the better understanding about the molecular mechanism of this disease from different perspectives. The top 100 genes in COPD-related metabolic network or COPD-related PPI network might be potential markers for the diagnosis and treatment of COPD.

Prior knowledge based mining functional modules from Yeast PPI networks with gene ontology

PubMed Central

2010-01-01

Background In the literature, there are fruitful algorithmic approaches for identification functional modules in protein-protein interactions (PPI) networks. Because of accumulation of large-scale interaction data on multiple organisms and non-recording interaction data in the existing PPI database, it is still emergent to design novel computational techniques that can be able to correctly and scalably analyze interaction data sets. Indeed there are a number of large scale biological data sets providing indirect evidence for protein-protein interaction relationships. Results The main aim of this paper is to present a prior knowledge based mining strategy to identify functional modules from PPI networks with the aid of Gene Ontology. Higher similarity value in Gene Ontology means that two gene products are more functionally related to each other, so it is better to group such gene products into one functional module. We study (i) to encode the functional pairs into the existing PPI networks; and (ii) to use these functional pairs as pairwise constraints to supervise the existing functional module identification algorithms. Topology-based modularity metric and complex annotation in MIPs will be used to evaluate the identified functional modules by these two approaches. Conclusions The experimental results on Yeast PPI networks and GO have shown that the prior knowledge based learning methods perform better than the existing algorithms. PMID:21172053

FUSE: a profit maximization approach for functional summarization of biological networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

2012-03-21

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

Genome-wide protein-protein interactions and protein function exploration in cyanobacteria

PubMed Central

Lv, Qi; Ma, Weimin; Liu, Hui; Li, Jiang; Wang, Huan; Lu, Fang; Zhao, Chen; Shi, Tieliu

2015-01-01

Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences, and “interologs” in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria. PMID:26490033

Filtering Gene Ontology semantic similarity for identifying protein complexes in large protein interaction networks.

PubMed

Wang, Jian; Xie, Dong; Lin, Hongfei; Yang, Zhihao; Zhang, Yijia

2012-06-21

Many biological processes recognize in particular the importance of protein complexes, and various computational approaches have been developed to identify complexes from protein-protein interaction (PPI) networks. However, high false-positive rate of PPIs leads to challenging identification. A protein semantic similarity measure is proposed in this study, based on the ontology structure of Gene Ontology (GO) terms and GO annotations to estimate the reliability of interactions in PPI networks. Interaction pairs with low GO semantic similarity are removed from the network as unreliable interactions. Then, a cluster-expanding algorithm is used to detect complexes with core-attachment structure on filtered network. Our method is applied to three different yeast PPI networks. The effectiveness of our method is examined on two benchmark complex datasets. Experimental results show that our method performed better than other state-of-the-art approaches in most evaluation metrics. The method detects protein complexes from large scale PPI networks by filtering GO semantic similarity. Removing interactions with low GO similarity significantly improves the performance of complex identification. The expanding strategy is also effective to identify attachment proteins of complexes.

Methods for protein complex prediction and their contributions towards understanding the organisation, function and dynamics of complexes.

PubMed

Srihari, Sriganesh; Yong, Chern Han; Patil, Ashwini; Wong, Limsoon

2015-09-14

Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organisation of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight their limitations and challenges, in particular at detecting sparse and small or sub-complexes and discerning overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Multi-agent-based bio-network for systems biology: protein-protein interaction network as an example.

PubMed

Ren, Li-Hong; Ding, Yong-Sheng; Shen, Yi-Zhen; Zhang, Xiang-Feng

2008-10-01

Recently, a collective effort from multiple research areas has been made to understand biological systems at the system level. This research requires the ability to simulate particular biological systems as cells, organs, organisms, and communities. In this paper, a novel bio-network simulation platform is proposed for system biology studies by combining agent approaches. We consider a biological system as a set of active computational components interacting with each other and with an external environment. Then, we propose a bio-network platform for simulating the behaviors of biological systems and modelling them in terms of bio-entities and society-entities. As a demonstration, we discuss how a protein-protein interaction (PPI) network can be seen as a society of autonomous interactive components. From interactions among small PPI networks, a large PPI network can emerge that has a remarkable ability to accomplish a complex function or task. We also simulate the evolution of the PPI networks by using the bio-operators of the bio-entities. Based on the proposed approach, various simulators with different functions can be embedded in the simulation platform, and further research can be done from design to development, including complexity validation of the biological system.

Development and application of a DNA microarray-based yeast two-hybrid system

PubMed Central

Suter, Bernhard; Fontaine, Jean-Fred; Yildirimman, Reha; Raskó, Tamás; Schaefer, Martin H.; Rasche, Axel; Porras, Pablo; Vázquez-Álvarez, Blanca M.; Russ, Jenny; Rau, Kirstin; Foulle, Raphaele; Zenkner, Martina; Saar, Kathrin; Herwig, Ralf; Andrade-Navarro, Miguel A.; Wanker, Erich E.

2013-01-01

The yeast two-hybrid (Y2H) system is the most widely applied methodology for systematic protein–protein interaction (PPI) screening and the generation of comprehensive interaction networks. We developed a novel Y2H interaction screening procedure using DNA microarrays for high-throughput quantitative PPI detection. Applying a global pooling and selection scheme to a large collection of human open reading frames, proof-of-principle Y2H interaction screens were performed for the human neurodegenerative disease proteins huntingtin and ataxin-1. Using systematic controls for unspecific Y2H results and quantitative benchmarking, we identified and scored a large number of known and novel partner proteins for both huntingtin and ataxin-1. Moreover, we show that this parallelized screening procedure and the global inspection of Y2H interaction data are uniquely suited to define specific PPI patterns and their alteration by disease-causing mutations in huntingtin and ataxin-1. This approach takes advantage of the specificity and flexibility of DNA microarrays and of the existence of solid-related statistical methods for the analysis of DNA microarray data, and allows a quantitative approach toward interaction screens in human and in model organisms. PMID:23275563

Identifying protein complex by integrating characteristic of core-attachment into dynamic PPI network.

PubMed

Shen, Xianjun; Yi, Li; Jiang, Xingpeng; He, Tingting; Yang, Jincai; Xie, Wei; Hu, Po; Hu, Xiaohua

2017-01-01

How to identify protein complex is an important and challenging task in proteomics. It would make great contribution to our knowledge of molecular mechanism in cell life activities. However, the inherent organization and dynamic characteristic of cell system have rarely been incorporated into the existing algorithms for detecting protein complexes because of the limitation of protein-protein interaction (PPI) data produced by high throughput techniques. The availability of time course gene expression profile enables us to uncover the dynamics of molecular networks and improve the detection of protein complexes. In order to achieve this goal, this paper proposes a novel algorithm DCA (Dynamic Core-Attachment). It detects protein-complex core comprising of continually expressed and highly connected proteins in dynamic PPI network, and then the protein complex is formed by including the attachments with high adhesion into the core. The integration of core-attachment feature into the dynamic PPI network is responsible for the superiority of our algorithm. DCA has been applied on two different yeast dynamic PPI networks and the experimental results show that it performs significantly better than the state-of-the-art techniques in terms of prediction accuracy, hF-measure and statistical significance in biology. In addition, the identified complexes with strong biological significance provide potential candidate complexes for biologists to validate.

OncoPPi-informed discovery of mitogen-activated protein kinase kinase 3 as a novel binding partner of c-Myc | Office of Cancer Genomics

Cancer.gov

Mitogen-activated protein kinase kinase 3 (MKK3) is a dual threonine/tyrosine protein kinase that regulates inflammation, proliferation and apoptosis through specific phosphorylation and activation of the p38 mitogen-activated protein kinase. However, the role of MKK3 beyond p38-signaling remains elusive. Recently, we reported a protein-protein interaction (PPI) network of cancer-associated genes, termed OncoPPi, as a resource for the scientific community to generate new biological models. Analysis of the OncoPPi connectivity identified MKK3 as one of the major hub proteins in the network.

Disease gene classification with metagraph representations.

PubMed

Kircali Ata, Sezin; Fang, Yuan; Wu, Min; Li, Xiao-Li; Xiao, Xiaokui

2017-12-01

Protein-protein interaction (PPI) networks play an important role in studying the functional roles of proteins, including their association with diseases. However, protein interaction networks are not sufficient without the support of additional biological knowledge for proteins such as their molecular functions and biological processes. To complement and enrich PPI networks, we propose to exploit biological properties of individual proteins. More specifically, we integrate keywords describing protein properties into the PPI network, and construct a novel PPI-Keywords (PPIK) network consisting of both proteins and keywords as two different types of nodes. As disease proteins tend to have a similar topological characteristics on the PPIK network, we further propose to represent proteins with metagraphs. Different from a traditional network motif or subgraph, a metagraph can capture a particular topological arrangement involving the interactions/associations between both proteins and keywords. Based on the novel metagraph representations for proteins, we further build classifiers for disease protein classification through supervised learning. Our experiments on three different PPI databases demonstrate that the proposed method consistently improves disease protein prediction across various classifiers, by 15.3% in AUC on average. It outperforms the baselines including the diffusion-based methods (e.g., RWR) and the module-based methods by 13.8-32.9% for overall disease protein prediction. For predicting breast cancer genes, it outperforms RWR, PRINCE and the module-based baselines by 6.6-14.2%. Finally, our predictions also turn out to have better correlations with literature findings from PubMed. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative proteomic analysis provides insight into the biological role of protein phosphatase inhibitor-2 from Arabidopsis.

PubMed

Ahsan, Nagib; Chen, Mingjie; Salvato, Fernanda; Wilson, Rashaun S; Shyama Prasad Rao, R; Thelen, Jay J

2017-08-08

Protein phosphatase inhibitor-2 (PPI-2) is a conserved eukaryotic effector protein that inhibits type one protein phosphatases (TOPP). A transfer-DNA knockdown of AtPPI-2 resulted in stunted growth in both vegetative and reproductive phases of Arabidopsis development. At the cellular level, AtPPI-2 knockdown had 35 to 40% smaller cells in developing roots and leaves. This developmental phenotype was rescued by transgenic expression of the AtPPI-2 cDNA behind a constitutive promoter. Comparative proteomics of developing leaves of wild type (WT) and AtPPI-2 mutant revealed reduced levels of proteins associated with chloroplast development, ribosome biogenesis, transport, and cell cycle regulation processes. Decreased abundance of several ribosomal proteins, a DEAD box RNA helicase family protein (AtRH3), Clp protease (ClpP3) and proteins associated with cell division suggests a bottleneck in chloroplast ribosomal biogenesis and cell cycle regulation in AtPPI-2 mutant plants. In contrast, eight out of nine Arabidopsis TOPP isoforms were increased at the transcript level in AtPPI-2 leaves compared to WT. A protein-protein interaction network revealed that >75% of the differentially accumulated proteins have at least secondary and/or tertiary connections with AtPPI-2. Collectively, these data reveal a potential basis for the growth defects of AtPPI-2 and support the presumed role of AtPPI-2 as a master regulator for TOPPs, which regulate diverse growth and developmental processes. Comparative label-free proteomics was used to characterize an AtPPI-2T-DNA knockdown mutant. The complex, reduced growth phenotype supports the notion that AtPPI-2 is a global regulator of TOPPs, and possibly other proteins. Comparative proteomics revealed a range of differences in protein abundance from various cellular processes such as chloroplast development, ribosome biogenesis, and transporter activity in the AtPPI-2 mutant relative to WT Arabidopsis. Collectively the results of proteomic analysis and the protein-protein network suggest that AtPPI-2 is involved in a wide range of biological processes either directly or indirectly including plastid biogenesis, translational mechanisms, and cell cycle regulation. The proposed protein interaction network comprises a testable model underlying changes in protein abundance in the AtPPI-2 mutant, and provides a better framework for future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

The autophagy interaction network of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

2017-03-27

Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables further specific studies to understand autophagy and aging in P. anserina as well as in other systems.

Using PPI network autocorrelation in hierarchical multi-label classification trees for gene function prediction.

PubMed

Stojanova, Daniela; Ceci, Michelangelo; Malerba, Donato; Dzeroski, Saso

2013-09-26

Ontologies and catalogs of gene functions, such as the Gene Ontology (GO) and MIPS-FUN, assume that functional classes are organized hierarchically, that is, general functions include more specific ones. This has recently motivated the development of several machine learning algorithms for gene function prediction that leverages on this hierarchical organization where instances may belong to multiple classes. In addition, it is possible to exploit relationships among examples, since it is plausible that related genes tend to share functional annotations. Although these relationships have been identified and extensively studied in the area of protein-protein interaction (PPI) networks, they have not received much attention in hierarchical and multi-class gene function prediction. Relations between genes introduce autocorrelation in functional annotations and violate the assumption that instances are independently and identically distributed (i.i.d.), which underlines most machine learning algorithms. Although the explicit consideration of these relations brings additional complexity to the learning process, we expect substantial benefits in predictive accuracy of learned classifiers. This article demonstrates the benefits (in terms of predictive accuracy) of considering autocorrelation in multi-class gene function prediction. We develop a tree-based algorithm for considering network autocorrelation in the setting of Hierarchical Multi-label Classification (HMC). We empirically evaluate the proposed algorithm, called NHMC (Network Hierarchical Multi-label Classification), on 12 yeast datasets using each of the MIPS-FUN and GO annotation schemes and exploiting 2 different PPI networks. The results clearly show that taking autocorrelation into account improves the predictive performance of the learned models for predicting gene function. Our newly developed method for HMC takes into account network information in the learning phase: When used for gene function prediction in the context of PPI networks, the explicit consideration of network autocorrelation increases the predictive performance of the learned models. Overall, we found that this holds for different gene features/ descriptions, functional annotation schemes, and PPI networks: Best results are achieved when the PPI network is dense and contains a large proportion of function-relevant interactions.

Rhizoma Dioscoreae extract protects against alveolar bone loss by regulating the cell cycle: A predictive study based on the protein‑protein interaction network.

PubMed

Zhang, Zhi-Guo; Song, Chang-Heng; Zhang, Fang-Zhen; Chen, Yan-Jing; Xiang, Li-Hua; Xiao, Gary Guishan; Ju, Da-Hong

2016-06-01

Rhizoma Dioscoreae extract (RDE) exhibits a protective effect on alveolar bone loss in ovariectomized (OVX) rats. The aim of this study was to predict the pathways or targets that are regulated by RDE, by re‑assessing our previously reported data and conducting a protein‑protein interaction (PPI) network analysis. In total, 383 differentially expressed genes (≥3‑fold) between alveolar bone samples from the RDE and OVX group rats were identified, and a PPI network was constructed based on these genes. Furthermore, four molecular clusters (A‑D) in the PPI network with the smallest P‑values were detected by molecular complex detection (MCODE) algorithm. Using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA) tools, two molecular clusters (A and B) were enriched for biological process in Gene Ontology (GO). Only cluster A was associated with biological pathways in the IPA database. GO and pathway analysis results showed that cluster A, associated with cell cycle regulation, was the most important molecular cluster in the PPI network. In addition, cyclin‑dependent kinase 1 (CDK1) may be a key molecule achieving the cell‑cycle‑regulatory function of cluster A. From the PPI network analysis, it was predicted that delayed cell cycle progression in excessive alveolar bone remodeling via downregulation of CDK1 may be another mechanism underling the anti‑osteopenic effect of RDE on alveolar bone.

FACETS: multi-faceted functional decomposition of protein interaction networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes

2012-10-15

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein-protein interaction (PPI) network using graph theoretic analysis. Despite the recent progress, systems level analysis of high-throughput PPIs remains a daunting task because of the amount of data they present. In this article, we propose a novel PPI network decomposition algorithm called FACETS in order to make sense of the deluge of interaction data using Gene Ontology (GO) annotations. FACETS finds not just a single functional decomposition of the PPI network, but a multi-faceted atlas of functional decompositions that portray alternative perspectives of the functional landscape of the underlying PPI network. Each facet in the atlas represents a distinct interpretation of how the network can be functionally decomposed and organized. Our algorithm maximizes interpretative value of the atlas by optimizing inter-facet orthogonality and intra-facet cluster modularity. We tested our algorithm on the global networks from IntAct, and compared it with gold standard datasets from MIPS and KEGG. We demonstrated the performance of FACETS. We also performed a case study that illustrates the utility of our approach. Supplementary data are available at the Bioinformatics online. Our software is available freely for non-commercial purposes from: http://www.cais.ntu.edu.sg/~assourav/Facets/

Predicting overlapping protein complexes from weighted protein interaction graphs by gradually expanding dense neighborhoods.

PubMed

Dimitrakopoulos, Christos; Theofilatos, Konstantinos; Pegkas, Andreas; Likothanassis, Spiros; Mavroudi, Seferina

2016-07-01

Proteins are vital biological molecules driving many fundamental cellular processes. They rarely act alone, but form interacting groups called protein complexes. The study of protein complexes is a key goal in systems biology. Recently, large protein-protein interaction (PPI) datasets have been published and a plethora of computational methods that provide new ideas for the prediction of protein complexes have been implemented. However, most of the methods suffer from two major limitations: First, they do not account for proteins participating in multiple functions and second, they are unable to handle weighted PPI graphs. Moreover, the problem remains open as existing algorithms and tools are insufficient in terms of predictive metrics. In the present paper, we propose gradually expanding neighborhoods with adjustment (GENA), a new algorithm that gradually expands neighborhoods in a graph starting from highly informative "seed" nodes. GENA considers proteins as multifunctional molecules allowing them to participate in more than one protein complex. In addition, GENA accepts weighted PPI graphs by using a weighted evaluation function for each cluster. In experiments with datasets from Saccharomyces cerevisiae and human, GENA outperformed Markov clustering, restricted neighborhood search and clustering with overlapping neighborhood expansion, three state-of-the-art methods for computationally predicting protein complexes. Seven PPI networks and seven evaluation datasets were used in total. GENA outperformed existing methods in 16 out of 18 experiments achieving an average improvement of 5.5% when the maximum matching ratio metric was used. Our method was able to discover functionally homogeneous protein clusters and uncover important network modules in a Parkinson expression dataset. When used on the human networks, around 47% of the detected clusters were enriched in gene ontology (GO) terms with depth higher than five in the GO hierarchy. In the present manuscript, we introduce a new method for the computational prediction of protein complexes by making the realistic assumption that proteins participate in multiple protein complexes and cellular functions. Our method can detect accurate and functionally homogeneous clusters. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying protein complexes in PPI network using non-cooperative sequential game.

PubMed

Maulik, Ujjwal; Basu, Srinka; Ray, Sumanta

2017-08-21

Identifying protein complexes from protein-protein interaction (PPI) network is an important and challenging task in computational biology as it helps in better understanding of cellular mechanisms in various organisms. In this paper we propose a noncooperative sequential game based model for protein complex detection from PPI network. The key hypothesis is that protein complex formation is driven by mechanism that eventually optimizes the number of interactions within the complex leading to dense subgraph. The hypothesis is drawn from the observed network property named small world. The proposed multi-player game model translates the hypothesis into the game strategies. The Nash equilibrium of the game corresponds to a network partition where each protein either belong to a complex or form a singleton cluster. We further propose an algorithm to find the Nash equilibrium of the sequential game. The exhaustive experiment on synthetic benchmark and real life yeast networks evaluates the structural as well as biological significance of the network partitions.

ChiPPI: a novel method for mapping chimeric protein-protein interactions uncovers selection principles of protein fusion events in cancer.

PubMed

Frenkel-Morgenstern, Milana; Gorohovski, Alessandro; Tagore, Somnath; Sekar, Vaishnovi; Vazquez, Miguel; Valencia, Alfonso

2017-07-07

Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins. Mapping the influence of fusion proteins on cell metabolism and pathways reveals that ChiPPI networks often lose tumor suppressor proteins and gain oncoproteins. Furthermore, fusions often induce novel connections between non-interactors skewing interaction networks and signaling pathways. We compared fusion protein PPI networks in leukemia/lymphoma, sarcoma and solid tumors finding distinct enrichment patterns for each disease type. While certain pathways are enriched in all three diseases (Wnt, Notch and TGF β), there are distinct patterns for leukemia (EGFR signaling, DNA replication and CCKR signaling), for sarcoma (p53 pathway and CCKR signaling) and solid tumors (FGFR and EGFR signaling). Thus, the ChiPPI method represents a comprehensive tool for studying the anomaly of skewed cellular networks produced by fusion proteins in cancer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Querying graphs in protein-protein interactions networks using feedback vertex set.

PubMed

Blin, Guillaume; Sikora, Florian; Vialette, Stéphane

2010-01-01

Recent techniques increase rapidly the amount of our knowledge on interactions between proteins. The interpretation of these new information depends on our ability to retrieve known substructures in the data, the Protein-Protein Interactions (PPIs) networks. In an algorithmic point of view, it is an hard task since it often leads to NP-hard problems. To overcome this difficulty, many authors have provided tools for querying patterns with a restricted topology, i.e., paths or trees in PPI networks. Such restriction leads to the development of fixed parameter tractable (FPT) algorithms, which can be practicable for restricted sizes of queries. Unfortunately, Graph Homomorphism is a W[1]-hard problem, and hence, no FPT algorithm can be found when patterns are in the shape of general graphs. However, Dost et al. gave an algorithm (which is not implemented) to query graphs with a bounded treewidth in PPI networks (the treewidth of the query being involved in the time complexity). In this paper, we propose another algorithm for querying pattern in the shape of graphs, also based on dynamic programming and the color-coding technique. To transform graphs queries into trees without loss of informations, we use feedback vertex set coupled to a node duplication mechanism. Hence, our algorithm is FPT for querying graphs with a bounded size of their feedback vertex set. It gives an alternative to the treewidth parameter, which can be better or worst for a given query. We provide a python implementation which allows us to validate our implementation on real data. Especially, we retrieve some human queries in the shape of graphs into the fly PPI network.

Systems-level analysis of risk genes reveals the modular nature of schizophrenia.

PubMed

Liu, Jiewei; Li, Ming; Luo, Xiong-Jian; Su, Bing

2018-05-19

Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent genome-wide association studies) have identified many risk genes for schizophrenia. However, the physical interactions among the proteins encoded by schizophrenia risk genes remain elusive and it is not known whether the identified risk genes converge on common molecular networks or pathways. Here we systematically investigated the network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions (PPI) from the human interactome. We found that schizophrenia risk genes encode a densely interconnected PPI network (P = 4.15 × 10 -31 ). Compared with the background genes, the schizophrenia risk genes in the interactome have significantly higher degree (P = 5.39 × 10 -11 ), closeness centrality (P = 7.56 × 10 -11 ), betweeness centrality (P = 1.29 × 10 -11 ), clustering coefficient (P = 2.22 × 10 -2 ), and shorter average shortest path length (P = 7.56 × 10 -11 ). Based on the densely interconnected PPI network, we identified 48 hub genes and 4 modules formed by highly interconnected schizophrenia genes. We showed that the proteins encoded by schizophrenia hub genes have significantly more direct physical interactions. Gene ontology (GO) analysis revealed that cell adhesion, cell cycle, immune system response, and GABR-receptor complex categories were enriched in the modules formed by highly interconnected schizophrenia risk genes. Our study reveals that schizophrenia risk genes encode a densely interconnected molecular network and demonstrates the modular nature of schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

PubMed

Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

2007-09-01

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Proteome-scale human interactomics

PubMed Central

Luck, Katja; Sheynkman, Gloria M.; Zhang, Ivy; Vidal, Marc

2017-01-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome-scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. PMID:28284537

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis.

PubMed

Heekeren, K; Neukirch, A; Daumann, J; Stoll, M; Obradovic, M; Kovar, K-A; Geyer, M A; Gouzoulis-Mayfrank, E

2007-05-01

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

Reinforce: An Ensemble Approach for Inferring PPI Network from AP-MS Data.

PubMed

Tian, Bo; Duan, Qiong; Zhao, Can; Teng, Ben; He, Zengyou

2017-05-17

Affinity Purification-Mass Spectrometry (AP-MS) is one of the most important technologies for constructing protein-protein interaction (PPI) networks. In this paper, we propose an ensemble method, Reinforce, for inferring PPI network from AP-MS data set. The new algorithm named Reinforce is based on rank aggregation and false discovery rate control. Under the null hypothesis that the interaction scores from different scoring methods are randomly generated, Reinforce follows three steps to integrate multiple ranking results from different algorithms or different data sets. The experimental results show that Reinforce can get more stable and accurate inference results than existing algorithms. The source codes of Reinforce and data sets used in the experiments are available at: https://sourceforge.net/projects/reinforce/.

Protein-protein interaction network of gene expression in the hydrocortisone-treated keloid.

PubMed

Chen, Rui; Zhang, Zhiliang; Xue, Zhujia; Wang, Lin; Fu, Mingang; Lu, Yi; Bai, Ling; Zhang, Ping; Fan, Zhihong

2015-01-01

In order to explore the molecular mechanism of hydrocortisone in keloid tissue, the gene expression profiles of keloid samples treated with hydrocortisone were subjected to bioinformatics analysis. Firstly, the gene expression profiles (GSE7890) of five samples of keloid treated with hydrocortisone and five untreated keloid samples were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, data were preprocessed using packages in R language and differentially expressed genes (DEGs) were screened using a significance analysis of microarrays (SAM) protocol. Thirdly, the DEGs were subjected to gene ontology (GO) function and KEGG pathway enrichment analysis. Finally, the interactions of DEGs in samples of keloid treated with hydrocortisone were explored in a human protein-protein interaction (PPI) network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software. Based on the analysis, 572 DEGs in the hydrocortisone-treated samples were screened; most of these were involved in the signal transduction and cell cycle. Furthermore, three critical genes in the module, including COL1A1, NID1, and PRELP, were screened in the PPI network analysis. These findings enhance understanding of the pathogenesis of the keloid and provide references for keloid therapy. © 2015 The International Society of Dermatology.

A novel one-class SVM based negative data sampling method for reconstructing proteome-wide HTLV-human protein interaction networks.

PubMed

Mei, Suyu; Zhu, Hao

2015-01-26

Protein-protein interaction (PPI) prediction is generally treated as a problem of binary classification wherein negative data sampling is still an open problem to be addressed. The commonly used random sampling is prone to yield less representative negative data with considerable false negatives. Meanwhile rational constraints are seldom exerted on model selection to reduce the risk of false positive predictions for most of the existing computational methods. In this work, we propose a novel negative data sampling method based on one-class SVM (support vector machine, SVM) to predict proteome-wide protein interactions between HTLV retrovirus and Homo sapiens, wherein one-class SVM is used to choose reliable and representative negative data, and two-class SVM is used to yield proteome-wide outcomes as predictive feedback for rational model selection. Computational results suggest that one-class SVM is more suited to be used as negative data sampling method than two-class PPI predictor, and the predictive feedback constrained model selection helps to yield a rational predictive model that reduces the risk of false positive predictions. Some predictions have been validated by the recent literature. Lastly, gene ontology based clustering of the predicted PPI networks is conducted to provide valuable cues for the pathogenesis of HTLV retrovirus.

FACETS: multi-faceted functional decomposition of protein interaction networks

PubMed Central

Seah, Boon-Siew; Bhowmick, Sourav S.; Forbes Dewey, C.

2012-01-01

Motivation: The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein–protein interaction (PPI) network using graph theoretic analysis. Despite the recent progress, systems level analysis of high-throughput PPIs remains a daunting task because of the amount of data they present. In this article, we propose a novel PPI network decomposition algorithm called FACETS in order to make sense of the deluge of interaction data using Gene Ontology (GO) annotations. FACETS finds not just a single functional decomposition of the PPI network, but a multi-faceted atlas of functional decompositions that portray alternative perspectives of the functional landscape of the underlying PPI network. Each facet in the atlas represents a distinct interpretation of how the network can be functionally decomposed and organized. Our algorithm maximizes interpretative value of the atlas by optimizing inter-facet orthogonality and intra-facet cluster modularity. Results: We tested our algorithm on the global networks from IntAct, and compared it with gold standard datasets from MIPS and KEGG. We demonstrated the performance of FACETS. We also performed a case study that illustrates the utility of our approach. Contact: seah0097@ntu.edu.sg or assourav@ntu.edu.sg Supplementary information: Supplementary data are available at the Bioinformatics online. Availability: Our software is available freely for non-commercial purposes from: http://www.cais.ntu.edu.sg/∼assourav/Facets/ PMID:22908217

CellMap visualizes protein-protein interactions and subcellular localization

PubMed Central

Dallago, Christian; Goldberg, Tatyana; Andrade-Navarro, Miguel Angel; Alanis-Lobato, Gregorio; Rost, Burkhard

2018-01-01

Many tools visualize protein-protein interaction (PPI) networks. The tool introduced here, CellMap, adds one crucial novelty by visualizing PPI networks in the context of subcellular localization, i.e. the location in the cell or cellular component in which a PPI happens. Users can upload images of cells and define areas of interest against which PPIs for selected proteins are displayed (by default on a cartoon of a cell). Annotations of localization are provided by the user or through our in-house database. The visualizer and server are written in JavaScript, making CellMap easy to customize and to extend by researchers and developers. PMID:29497493

Sexual orientation-related differences in prepulse inhibition of the human startle response.

PubMed

Rahman, Qazi; Kumari, Veena; Wilson, Glenn D

2003-10-01

Prepulse inhibition (PPI) refers to a reduction in the startle response to a strong sensory stimulus when this stimulus is preceded by a weaker stimulus--the prepulse. PPI reflects a nonlearned sensorimotor gating mechanism and also shows a robust gender difference, with women exhibiting lower PPI than men. The present study examined the eyeblink startle responses to acoustic stimuli of 59 healthy heterosexual and homosexual men and women. Homosexual women showed significantly masculinized PPI compared with heterosexual women, whereas no difference was observed in PPI between homosexual and heterosexual men. These data provide the first evidence for within-gender differences in basic sensorimotor gating mechanisms and implicate the known neural substrates of PPI in human sexual orientation. (c) 2003 APA, all rights reserved

atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

PubMed

Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-07-20

Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

Discovering disease-associated genes in weighted protein-protein interaction networks

NASA Astrophysics Data System (ADS)

Cui, Ying; Cai, Meng; Stanley, H. Eugene

2018-04-01

Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

Proteome-Scale Human Interactomics.

PubMed

Luck, Katja; Sheynkman, Gloria M; Zhang, Ivy; Vidal, Marc

2017-05-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discovering protein complexes in protein interaction networks via exploring the weak ties effect

PubMed Central

2012-01-01

Background Studying protein complexes is very important in biological processes since it helps reveal the structure-functionality relationships in biological networks and much attention has been paid to accurately predict protein complexes from the increasing amount of protein-protein interaction (PPI) data. Most of the available algorithms are based on the assumption that dense subgraphs correspond to complexes, failing to take into account the inherence organization within protein complex and the roles of edges. Thus, there is a critical need to investigate the possibility of discovering protein complexes using the topological information hidden in edges. Results To provide an investigation of the roles of edges in PPI networks, we show that the edges connecting less similar vertices in topology are more significant in maintaining the global connectivity, indicating the weak ties phenomenon in PPI networks. We further demonstrate that there is a negative relation between the weak tie strength and the topological similarity. By using the bridges, a reliable virtual network is constructed, in which each maximal clique corresponds to the core of a complex. By this notion, the detection of the protein complexes is transformed into a classic all-clique problem. A novel core-attachment based method is developed, which detects the cores and attachments, respectively. A comprehensive comparison among the existing algorithms and our algorithm has been made by comparing the predicted complexes against benchmark complexes. Conclusions We proved that the weak tie effect exists in the PPI network and demonstrated that the density is insufficient to characterize the topological structure of protein complexes. Furthermore, the experimental results on the yeast PPI network show that the proposed method outperforms the state-of-the-art algorithms. The analysis of detected modules by the present algorithm suggests that most of these modules have well biological significance in context of complexes, suggesting that the roles of edges are critical in discovering protein complexes. PMID:23046740

Finding Correlation between Protein Protein Interaction Modules Using Semantic Web Techniques

NASA Astrophysics Data System (ADS)

Kargar, Mehdi; Moaven, Shahrouz; Abolhassani, Hassan

Many complex networks such as social networks and computer show modular structures, where edges between nodes are much denser within modules than between modules. It is strongly believed that cellular networks are also modular, reflecting the relative independence and coherence of different functional units in a cell. In this paper we used a human curated dataset. In this paper we consider each module in the PPI network as ontology. Using techniques in ontology alignment, we compare each pair of modules in the network. We want to see that is there a correlation between the structure of each module or they have totally different structures. Our results show that there is no correlation between proteins in a protein protein interaction network.

Identifying Hierarchical and Overlapping Protein Complexes Based on Essential Protein-Protein Interactions and “Seed-Expanding” Method

PubMed Central

Ren, Jun; Zhou, Wei; Wang, Jianxin

2014-01-01

Many evidences have demonstrated that protein complexes are overlapping and hierarchically organized in PPI networks. Meanwhile, the large size of PPI network wants complex detection methods have low time complexity. Up to now, few methods can identify overlapping and hierarchical protein complexes in a PPI network quickly. In this paper, a novel method, called MCSE, is proposed based on λ-module and “seed-expanding.” First, it chooses seeds as essential PPIs or edges with high edge clustering values. Then, it identifies protein complexes by expanding each seed to a λ-module. MCSE is suitable for large PPI networks because of its low time complexity. MCSE can identify overlapping protein complexes naturally because a protein can be visited by different seeds. MCSE uses the parameter λ_th to control the range of seed expanding and can detect a hierarchical organization of protein complexes by tuning the value of λ_th. Experimental results of S. cerevisiae show that this hierarchical organization is similar to that of known complexes in MIPS database. The experimental results also show that MCSE outperforms other previous competing algorithms, such as CPM, CMC, Core-Attachment, Dpclus, HC-PIN, MCL, and NFC, in terms of the functional enrichment and matching with known protein complexes. PMID:25143945

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets.

PubMed

Ho, Hsiang; Milenković, Tijana; Memisević, Vesna; Aruri, Jayavani; Przulj, Natasa; Ganesan, Anand K

2010-06-15

RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets

PubMed Central

2010-01-01

Background RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. Results In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. Conclusions We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches. PMID:20550706

"Pollical palmar interosseous muscle" (musculus adductor pollicis accessorius): attachments, innervation, variations, phylogeny, and implications for human evolution and medicine.

PubMed

Bello-Hellegouarch, Gaelle; Aziz, M Ashraf; Ferrero, Eva M; Kern, Michael; Francis, Nadia; Diogo, Rui

2013-03-01

Most atlases and textbooks dealing with human anatomy do not refer to the "pollical palmar interosseous" (PPI) muscle of Henle. In order to undertake a fresh and detailed study of this muscle and to thus better understand human comparative anatomy and evolution, we: 1) analyze the frequency of the PPI in a large sample of human hands; 2) describe the attachments, innervation and varieties of the PPI in these hands; 3) compare the data obtained with the information available in the literature; and 4) discuss the phylogenetic origin of the PPI and the implications of our observations and comparisons for medicine and for the understanding of human evolutionary history. Within the 72 hands dissected by us, the PPI is present in 67 hands (93%), commonly having a single muscular branch, originating from the medial side of the base of metacarpal I only, inserting onto the medial side of the base of the pollical proximal phalanx and/or surrounding structures (e.g., ulnar sesamoid bone, wing tendon of extensor apparatus), and passing at least partially, and usually mainly, medial to the princeps pollicis artery. A careful study of the human PPI, as well as a detailed comparison with other mammals, strongly suggest that the muscle is evolutionarily derived from the adductor pollicis, and namely from its oblique head. Therefore, we propose that PPI should be designated by the name musculus adductor pollicis accessorius, which indicates that the muscle is most likely a de novo structure derived from the adductor pollicis. Copyright © 2012 Wiley Periodicals, Inc.

Identification of potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma.

PubMed

Pan, Yue; Lu, Lingyun; Chen, Junquan; Zhong, Yong; Dai, Zhehao

2018-01-01

This study aimed to identify potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma by comprehensive bioinformatics analysis. Data of gene expression profiles (GSE28424) and miRNA expression profiles (GSE28423) were downloaded from GEO database. The differentially expressed genes (DEGs) and miRNAs (DEMIs) were obtained by R Bioconductor packages. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. The relationships among the DEGs and module in PPI network were analyzed by plug-in NetworkAnalyzer and MCODE seperately. Through the TargetScan and comparing target genes with DEGs, the miRNA-mRNA regulation network was established. Totally 346 DEGs and 90 DEMIs were found to be differentially expressed. These DEGs were enriched in biological processes and KEGG pathway of inflammatory immune response. 25 genes in the PPI network were selected as hub genes. Top 10 hub genes were TYROBP, HLA-DRA, VWF, PPBP, SERPING1, HLA-DPA1, SERPINA1, KIF20A, FERMT3, HLA-E. PPI network of DEGs followed a pattern of power law network and met the characteristics of small-world network. MCODE analysis identified 4 clusters and the most significant cluster consisted of 11 nodes and 55 edges. SEPP1, CKS2, TCAP, BPI were identified as the seed genes in their own clusters, respectively. The miRNA-mRNA regulation network which was composed of 89 pairs was established. MiR-210 had the highest connectivity with 12 target genes. Among the predicted target of MiR-96, HLA-DPA1 and TYROBP were the hub genes. Our study indicated possible differentially expressed genes and miRNA, and microRNA-mRNA negative regulatory networks in osteosarcoma by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of osteosarcoma.

Flexible regenerated cellulose/polypyrrole composite films with enhanced dielectric properties.

PubMed

Raghunathan, Sreejesh Poikavila; Narayanan, Sona; Poulose, Aby Cheruvathur; Joseph, Rani

2017-02-10

Flexible regenerated cellulose/polypyrrole (RC-PPy) conductive composite films were prepared by insitu polymerization of pyrrole on regenerated cellulose (RC) matrix using ammonium persulphate as oxidant. FTIR, XPS and XRD analysis of RC-PPy composite films revealed strong interaction between polypyrrole (PPy) and RC matrix. XRD results indicated that crystalline structure of RC matrix remains intact even after composite formation. SEM micrographs revealed the formation of a continuous conductive network of PPy particles in the RC matrix, leading to significant improvement in electrical and dielectric properties. The electrical conductivity of RC-PPy composites with 12wt% of PPy was 3.2×10 -5 S/cm, which is approximately seven fold higher than that of RC. Composites showed high dielectric constant and low dielectric loss values, which is essential in capacitor application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat

PubMed Central

Webber, Emily S.; Mankin, David E.; McGraw, Justin J.; Beckwith, Travis J.; Cromwell, Howard C.

2013-01-01

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50 kHz USV emission. Rats emitted high levels of 22 kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. PMID:23850353

Finding trans-regulatory genes and protein complexes modulating meiotic recombination hotspots of human, mouse and yeast.

PubMed

Wu, Min; Kwoh, Chee-Keong; Li, Xiaoli; Zheng, Jie

2014-09-11

The regulatory mechanism of recombination is one of the most fundamental problems in genomics, with wide applications in genome wide association studies (GWAS), birth-defect diseases, molecular evolution, cancer research, etc. Recombination events cluster into short genomic regions called "recombination hotspots". Recently, a zinc finger protein PRDM9 was reported to regulate recombination hotspots in human and mouse genomes. In addition, a 13-mer motif contained in the binding sites of PRDM9 is found to be enriched in human hotspots. However, this 13-mer motif only covers a fraction of hotspots, indicating that PRDM9 is not the only regulator of recombination hotspots. Therefore, the challenge of discovering other regulators of recombination hotspots becomes significant. Furthermore, recombination is a complex process. Hence, multiple proteins acting as machinery, rather than individual proteins, are more likely to carry out this process in a precise and stable manner. Therefore, the extension of the prediction of individual trans-regulators to protein complexes is also highly desired. In this paper, we introduce a pipeline to identify genes and protein complexes associated with recombination hotspots. First, we prioritize proteins associated with hotspots based on their preference of binding to hotspots and coldspots. Second, using the above identified genes as seeds, we apply the Random Walk with Restart algorithm (RWR) to propagate their influences to other proteins in protein-protein interaction (PPI) networks. Hence, many proteins without DNA-binding information will also be assigned a score to implicate their roles in recombination hotspots. Third, we construct sub-PPI networks induced by top genes ranked by RWR for various species (e.g., yeast, human and mouse) and detect protein complexes in those sub-PPI networks. The GO term analysis show that our prioritizing methods and the RWR algorithm are capable of identifying novel genes associated with recombination hotspots. The trans-regulators predicted by our pipeline are enriched with epigenetic functions (e.g., histone modifications), demonstrating the epigenetic regulatory mechanisms of recombination hotspots. The identified protein complexes also provide us with candidates to further investigate the molecular machineries for recombination hotspots. Moreover, the experimental data and results are available on our web site http://www.ntu.edu.sg/home/zhengjie/data/RecombinationHotspot/NetPipe/.

The role of HiPPI switches in mass storage systems: A five year prospective

NASA Technical Reports Server (NTRS)

Gilbert, T. A.

1992-01-01

New standards are evolving which provide the foundation for novel multi-gigabit per second data communication structures. The lowest layer protocols are so generalized that they encourage a wide range of application. Specifically, the ANSI High Performance Parallel Interface (HiPPI) is being applied to computer peripheral attachment as well as general data communication networks. This paper introduces the HiPPI standards suite and technology products which incorporate the standards. The use of simple HiPPI crosspoint switches to build potentially complex extended 'fabrics' is discussed in detail. Several near term applications of the HiPPI technology are briefly described with additional attention to storage systems. Finally, some related standards are mentioned which may further expand the concepts above.

The role of HiPPI switches in mass storage systems: A five year prospective

NASA Technical Reports Server (NTRS)

Gilbert, T. A.

1991-01-01

New standards are evolving which provide the foundation for multi-gigabit per second data communication structures. The lowest layer protocols are so generalized that they encourage a wide range of application. Specifically, the ANSI High Performance Parallel Interface (HiPPI) is being applied to computer peripheral attachment as well as general data communication networks. The HiPPI Standards suite and technology products which incorporate the standards are introduced. The use of simple HiPPI crosspoint switches to build potentially complex extended 'fabrics' is discussed in detail. Several near term applications of the HiPPI technology are briefly described with additional attention to storage systems. Finally, some related standards are mentioned which may further expand the concepts above.

Global Alignment of Pairwise Protein Interaction Networks for Maximal Common Conserved Patterns

DOE PAGES

Tian, Wenhong; Samatova, Nagiza F.

2013-01-01

A number of tools for the alignment of protein-protein interaction (PPI) networks have laid the foundation for PPI network analysis. Most of alignment tools focus on finding conserved interaction regions across the PPI networks through either local or global mapping of similar sequences. Researchers are still trying to improve the speed, scalability, and accuracy of network alignment. In view of this, we introduce a connected-components based fast algorithm, HopeMap, for network alignment. Observing that the size of true orthologs across species is small comparing to the total number of proteins in all species, we take a different approach based onmore » a precompiled list of homologs identified by KO terms. Applying this approach to S. cerevisiae (yeast) and D. melanogaster (fly), E. coli K12 and S. typhimurium , E. coli K12 and C. crescenttus , we analyze all clusters identified in the alignment. The results are evaluated through up-to-date known gene annotations, gene ontology (GO), and KEGG ortholog groups (KO). Comparing to existing tools, our approach is fast with linear computational cost, highly accurate in terms of KO and GO terms specificity and sensitivity, and can be extended to multiple alignments easily.« less

Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

PubMed

De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

2007-06-01

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.

Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Namaki, Saeed

2016-01-01

Background The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. Methods Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS vs. control) and PBMCs (relapse vs. remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression. Results The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse vs. remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS vs. control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse vs. remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways. Discussion This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets. PMID:28028462

Convergent roles of de novo mutations and common variants in schizophrenia in tissue-specific and spatiotemporal co-expression network.

PubMed

Jia, Peilin; Chen, Xiangning; Fanous, Ayman H; Zhao, Zhongming

2018-05-24

Genetic components susceptible to complex disease such as schizophrenia include a wide spectrum of variants, including common variants (CVs) and de novo mutations (DNMs). Although CVs and DNMs differ by origin, it remains elusive whether and how they interact at the gene, pathway, and network levels that leads to the disease. In this work, we characterized the genes harboring schizophrenia-associated CVs (CVgenes) and the genes harboring DNMs (DNMgenes) using measures from network, tissue-specific expression profile, and spatiotemporal brain expression profile. We developed an algorithm to link the DNMgenes and CVgenes in spatiotemporal brain co-expression networks. DNMgenes tended to have central roles in the human protein-protein interaction (PPI) network, evidenced in their high degree and high betweenness values. DNMgenes and CVgenes connected with each other significantly more often than with other genes in the networks. However, only CVgenes remained significantly connected after adjusting for their degree. In our gene co-expression PPI network, we found DNMgenes and CVgenes connected in a tissue-specific fashion, and such a pattern was similar to that in GTEx brain but not in other GTEx tissues. Importantly, DNMgene-CVgene subnetworks were enriched with pathways of chromatin remodeling, MHC protein complex binding, and neurotransmitter activities. In summary, our results unveiled that both DNMgenes and CVgenes contributed to a core set of biologically important pathways and networks, and their interactions may attribute to the risk for schizophrenia. Our results also suggested a stronger biological effect of DNMgenes than CVgenes in schizophrenia.

MCL-CAw: a refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

PubMed Central

2010-01-01

Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw. PMID:20939868

ModuleRole: a tool for modulization, role determination and visualization in protein-protein interaction networks.

PubMed

Li, Guipeng; Li, Ming; Zhang, Yiwei; Wang, Dong; Li, Rong; Guimerà, Roger; Gao, Juntao Tony; Zhang, Michael Q

2014-01-01

Rapidly increasing amounts of (physical and genetic) protein-protein interaction (PPI) data are produced by various high-throughput techniques, and interpretation of these data remains a major challenge. In order to gain insight into the organization and structure of the resultant large complex networks formed by interacting molecules, using simulated annealing, a method based on the node connectivity, we developed ModuleRole, a user-friendly web server tool which finds modules in PPI network and defines the roles for every node, and produces files for visualization in Cytoscape and Pajek. For given proteins, it analyzes the PPI network from BioGRID database, finds and visualizes the modules these proteins form, and then defines the role every node plays in this network, based on two topological parameters Participation Coefficient and Z-score. This is the first program which provides interactive and very friendly interface for biologists to find and visualize modules and roles of proteins in PPI network. It can be tested online at the website http://www.bioinfo.org/modulerole/index.php, which is free and open to all users and there is no login requirement, with demo data provided by "User Guide" in the menu Help. Non-server application of this program is considered for high-throughput data with more than 200 nodes or user's own interaction datasets. Users are able to bookmark the web link to the result page and access at a later time. As an interactive and highly customizable application, ModuleRole requires no expert knowledge in graph theory on the user side and can be used in both Linux and Windows system, thus a very useful tool for biologist to analyze and visualize PPI networks from databases such as BioGRID. ModuleRole is implemented in Java and C, and is freely available at http://www.bioinfo.org/modulerole/index.php. Supplementary information (user guide, demo data) is also available at this website. API for ModuleRole used for this program can be obtained upon request.

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat.

PubMed

Webber, Emily S; Mankin, David E; McGraw, Justin J; Beckwith, Travis J; Cromwell, Howard C

2013-09-15

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50kHz USV emission. Rats emitted high levels of 22kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related to the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. Copyright © 2013 Elsevier B.V. All rights reserved.

Network-Based Comparative Analysis of Arabidopsis Immune Responses to Golovinomyces orontii and Botrytis cinerea Infections.

PubMed

Jiang, Zhenhong; Dong, Xiaobao; Zhang, Ziding

2016-01-11

A comprehensive exploration of common and specific plant responses to biotrophs and necrotrophs is necessary for a better understanding of plant immunity. Here, we compared the Arabidopsis defense responses evoked by the biotrophic fungus Golovinomyces orontii and the necrotrophic fungus Botrytis cinerea through integrative network analysis. Two time-course transcriptional datasets were integrated with an Arabidopsis protein-protein interaction (PPI) network to construct a G. orontii conditional PPI sub-network (gCPIN) and a B. cinerea conditional PPI sub-network (bCPIN). We found that hubs in gCPIN and bCPIN played important roles in disease resistance. Hubs in bCPIN evolved faster than hubs in gCPIN, indicating the different selection pressures imposed on plants by different pathogens. By analyzing the common network from gCPIN and bCPIN, we identified two network components in which the genes were heavily involved in defense and development, respectively. The co-expression relationships between interacting proteins connecting the two components were different under G. orontii and B. cinerea infection conditions. Closer inspection revealed that auxin-related genes were overrepresented in the interactions connecting these two components, suggesting a critical role of auxin signaling in regulating the different co-expression relationships. Our work may provide new insights into plant defense responses against pathogens with different lifestyles.

Construction and analysis of protein-protein interaction networks based on proteomics data of prostate cancer

PubMed Central

CHEN, CHEN; SHEN, HONG; ZHANG, LI-GUO; LIU, JIAN; CAO, XIAO-GE; YAO, AN-LIANG; KANG, SHAO-SAN; GAO, WEI-XING; HAN, HUI; CAO, FENG-HONG; LI, ZHI-GUO

2016-01-01

Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa. PMID:27121963

Identification of Modules in Protein-Protein Interaction Networks

NASA Astrophysics Data System (ADS)

Erten, Sinan; Koyutürk, Mehmet

In biological systems, most processes are carried out through orchestration of multiple interacting molecules. These interactions are often abstracted using network models. A key feature of cellular networks is their modularity, which contributes significantly to the robustness, as well as adaptability of biological systems. Therefore, modularization of cellular networks is likely to be useful in obtaining insights into the working principles of cellular systems, as well as building tractable models of cellular organization and dynamics. A common, high-throughput source of data on molecular interactions is in the form of physical interactions between proteins, which are organized into protein-protein interaction (PPI) networks. This chapter provides an overview on identification and analysis of functional modules in PPI networks, which has been an active area of research in the last decade.

Predicting protein complexes from weighted protein-protein interaction graphs with a novel unsupervised methodology: Evolutionary enhanced Markov clustering.

PubMed

Theofilatos, Konstantinos; Pavlopoulou, Niki; Papasavvas, Christoforos; Likothanassis, Spiros; Dimitrakopoulos, Christos; Georgopoulos, Efstratios; Moschopoulos, Charalampos; Mavroudi, Seferina

2015-03-01

Proteins are considered to be the most important individual components of biological systems and they combine to form physical protein complexes which are responsible for certain molecular functions. Despite the large availability of protein-protein interaction (PPI) information, not much information is available about protein complexes. Experimental methods are limited in terms of time, efficiency, cost and performance constraints. Existing computational methods have provided encouraging preliminary results, but they phase certain disadvantages as they require parameter tuning, some of them cannot handle weighted PPI data and others do not allow a protein to participate in more than one protein complex. In the present paper, we propose a new fully unsupervised methodology for predicting protein complexes from weighted PPI graphs. The proposed methodology is called evolutionary enhanced Markov clustering (EE-MC) and it is a hybrid combination of an adaptive evolutionary algorithm and a state-of-the-art clustering algorithm named enhanced Markov clustering. EE-MC was compared with state-of-the-art methodologies when applied to datasets from the human and the yeast Saccharomyces cerevisiae organisms. Using public available datasets, EE-MC outperformed existing methodologies (in some datasets the separation metric was increased by 10-20%). Moreover, when applied to new human datasets its performance was encouraging in the prediction of protein complexes which consist of proteins with high functional similarity. In specific, 5737 protein complexes were predicted and 72.58% of them are enriched for at least one gene ontology (GO) function term. EE-MC is by design able to overcome intrinsic limitations of existing methodologies such as their inability to handle weighted PPI networks, their constraint to assign every protein in exactly one cluster and the difficulties they face concerning the parameter tuning. This fact was experimentally validated and moreover, new potentially true human protein complexes were suggested as candidates for further validation using experimental techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of polypyrrole-embedded electrospun poly(lactic acid) nanofibrous scaffolds for nerve tissue engineering

PubMed Central

Zhou, Jun-feng; Wang, Yi-guo; Cheng, Liang; Wu, Zhao; Sun, Xiao-dan; Peng, Jiang

2016-01-01

Polypyrrole (PPy) is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly(lactic acid) (PLA) nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topography. There was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration. PMID:27904497

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Gao, Shangzhi; Nguyen, Nam Ninh; Fan, Mengyuan; Jin, Jingjing; Liu, Bing; Zhao, Liang; Xiong, Geng; Tan, Min; Li, Shijun; Wong, Limsoon

2014-04-08

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies.

Association between arginine vasopressin 1a receptor (AVPR1a) promoter region polymorphisms and prepulse inhibition.

PubMed

Levin, Raz; Heresco-Levy, Uriel; Bachner-Melman, Rachel; Israel, Salomon; Shalev, Idan; Ebstein, Richard P

2009-07-01

Arginine vasopressin and the arginine vasopressin 1a (AVPR1a) gene contribute to a range of social behaviors both in lower vertebrates and in humans. Human promoter-region microsatellite repeat regions (RS1 and RS3) in the AVPR1a gene region have been associated with autism spectrum disorders, prosocial behavior and social cognition. Prepulse inhibition (PPI) of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. Reduced PPI has been observed in disorders including schizophrenia that are distinguished by deficits in social skills. In the current investigation association was examined between PPI and the AVPR1a RS1 and RS repeat regions and PPI in a group of 113 nonclinical subjects. Using a robust family-based strategy, association was observed between AVPR1a promoter-region repeat length, especially RS3) and PPI (30 ms: global p=0.04; 60 ms p=0.006; 120 ms p=0.008). Notably, longer RS3 alleles were associated with greater levels of prepulse inhibition. Using a short/long classification scheme for the repeat regions, significant association was also observed between all three PPI intervals (30, 60 and 120 ms) and both RS1 and RS3 polymorphisms (PBAT: FBAT-PC(2) statistic p=0.047). Tests of within-subject effects (SPSS GLM) showed significant sexxRS3 interactions at 30 ms (p=0.045) and 60 ms (p=0.01). Longer alleles, especially in male subjects, are associated with significantly higher PPI response, consistent with a role for the promoter repeat region in partially molding social behavior in both animals and humans. This is the first report in humans demonstrating a role of the AVPR1a gene in contributing to the PPI response to auditory stimuli.

Discovering functional interdependence relationship in PPI networks for protein complex identification.

PubMed

Lam, Winnie W M; Chan, Keith C C

2012-04-01

Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation, PCIFI was used to identify protein complexes in real PPI network data and the protein complexes it found were matched against those that were previously known in MIPS. The results show that PCIFI can be an effective technique for the identification of protein complexes. The protein complexes it found can match more known protein complexes with a smaller false-alarm rate and can provide useful insights into the understanding of the functional interdependence relationships between proteins in protein complexes.

Network topological analysis reveals the functional cohesiveness for the newly discovered links by Yeast 2 Hybrid approach

NASA Astrophysics Data System (ADS)

Ghiassian, Susan; Pevzner, Sam; Rolland, Thomas; Tassan, Murat; Barabasi, Albert Laszlo; Vidal, Mark; CCNR, Northeastern University Collaboration; Dana Farber Cancer Institute Collaboration

2014-03-01

Protein-protein interaction maps and interactomes are the blueprint of Network Medicine and systems biology and are being experimentally studied by different groups. Despite the wide usage of Literature Curated Interactome (LCI), these sources are biased towards different parameters such as highly studied proteins. Yeast two hybrid method is a high throughput experimental setup which screens proteins in an unbiased fashion. Current knowledge of protein interactions is far from complete. In fact the previous offered data from Y2H method (2005), is estimated to offer only 5% of all potential protein interactions. Currently this coverage has increased to 20% of what is known as reference HI In this work we study the topological properties of Y2H protein-protein interactions network with LCI and show although they both agree on some properties, LCI shows a clear unbiased nature of interaction selections. Most importantly, we assess the properties of PPI as it evolves with increasing the coverage. We show that, the newly discovered interactions tend to connect proteins that have been closer than average in the previous PPI release. reinforcing the modular structure of PPI. Furthermore, we show, some unseen effects on PPI (as opposed to LCI) can be explained by its incompleteness.

A systems biology approach to study systemic inflammation.

PubMed

Chen, Bor-Sen; Wu, Chia-Chou

2014-01-01

Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

Electrochemical and XPS study of LiFePO4 cathode nanocomposite with PPy/PEG conductive network

NASA Astrophysics Data System (ADS)

Fedorková, A.; Oriňáková, R.; Oriňák, A.; Kupková, M.; Wiemhöfer, H.-D.; Audinot, J. N.; Guillot, J.

2012-08-01

High performance PPy/PEG-LiFePO4 nanocomposites as cathode materials were synthesized by solvothermal method and simple chemical oxidative polymerization of pyrrole (Py) monomer on the surface of LiFePO4 particles. The samples were characterized by scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectrometry (XPS) and charge-discharge tests. PPyPEG hybrid layers decrease particle to particle contact resistance while the impedance measurements confirmed that the coating of PPy-PEG significantly decreases the charge transfer resistance of the electrode material. The initial discharge capacities of this sample at C/5 and 1C are 150 and 128 mAh/g, respectively. The results show that PPy/PEGLiFePO4 composites are more effective than bare LiFePO4 as cathode material.

Pharmacological interventions for stress ulcer prophylaxis in critically ill patients: a mixed treatment comparison network meta-analysis and a recursive cumulative meta-analysis.

PubMed

Sridharan, Kannan; Sivaramakrishnan, Gowri; Gnanaraj, Jerome

2018-02-01

Proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RA), sucralfate and antacids are the commonly administered agents for stress ulcer prophylaxis (SUP) in critically ill patients. The authors of this paper have conducted a network meta-analysis to compare the efficacy of these agents in SUP. Electronic databases were searched for randomized controlled trials, cohort studies and conference abstracts for studies comparing a SUP agent in critically ill patients to another active SUP agent or placebo. Overt, occult and clinically significant upper gastro-intestinal (UGI) bleeding, all-cause mortality, pneumonia, gastric colonization and ICU length of stay were considered as the outcome measures. A random effects model was used to generate pooled estimates. A total of 53 studies (4258 participants) were included. The pooled estimates were in favor of PPI and sucralfate for the overt UGI bleeding. PPI and H2RA bolus were associated with increased risk of gastric colonization and pneumonia. SUP in critically ill patients was not associated with any benefit with regard to clinically significant bleeding episodes. However, PPI and sucralfate significantly reduces overt UGI bleeding. On the contrary, PPI and H2RA bolus are associated with an increased risk of gastric colonization and pneumonia.

Revealing protein functions based on relationships of interacting proteins and GO terms.

PubMed

Teng, Zhixia; Guo, Maozu; Liu, Xiaoyan; Tian, Zhen; Che, Kai

2017-09-20

In recent years, numerous computational methods predicted protein function based on the protein-protein interaction (PPI) network. These methods supposed that two proteins share the same function if they interact with each other. However, it is reported by recent studies that the functions of two interacting proteins may be just related. It will mislead the prediction of protein function. Therefore, there is a need for investigating the functional relationship between interacting proteins. In this paper, the functional relationship between interacting proteins is studied and a novel method, called as GoDIN, is advanced to annotate functions of interacting proteins in Gene Ontology (GO) context. It is assumed that the functional difference between interacting proteins can be expressed by semantic difference between GO term and its relatives. Thus, the method uses GO term and its relatives to annotate the interacting proteins separately according to their functional roles in the PPI network. The method is validated by a series of experiments and compared with the concerned method. The experimental results confirm the assumption and suggest that GoDIN is effective on predicting functions of protein. This study demonstrates that: (1) interacting proteins are not equal in the PPI network, and their function may be same or similar, or just related; (2) functional difference between interacting proteins can be measured by their degrees in the PPI network; (3) functional relationship between interacting proteins can be expressed by relationship between GO term and its relatives.

Embedded Carbide-derived Carbon (CDC) particles in polypyrrole (PPy) for linear actuator

NASA Astrophysics Data System (ADS)

Zondaka, Zane; Valner, Robert; Aabloo, Alvo; Tamm, Tarmo; Kiefer, Rudolf

2016-04-01

Conducting polymer linear actuators, for example sodium dodecylbenzenesulfonate (NaDBS) doped polypyrrole (PPy/DBS), have shown moderate strain and stress. The goal of this work was to increase the obtainable strain and stress by adding additional active material to PPy/DBS. In recent year's carbide-derived carbon (CDC)-based materials have been applied in actuators; however, the obtained displacement and actuation speed has been low comparing to conducting polymer based actuators. In the present work, a CDC-PPy hybrid was synthesized electrochemically and polyoxometalate (POM) - phosphotungstic acid - was used to attach charge to CDC particles. The CDC-POM served in the presence of NaDBS as an additional electrolyte. Cyclic voltammetry and chronopotentiometric electrochemomechanical deformation (ECMD) measurements were performed in Lithium bis(trifluoromethanesulfonyl)- imide (LiTFSI) aqueous electrolyte. The ECMD measurements revealed that the hybrid CDC-PPy material exhibited higher force and strain in comparison to PPy/DBS films. The new material was investigated by scanning electron microscopy (SEM) to evaluate CDC particle embedding in the polymer network.

A hybrid network-based method for the detection of disease-related genes

NASA Astrophysics Data System (ADS)

Cui, Ying; Cai, Meng; Dai, Yang; Stanley, H. Eugene

2018-02-01

Detecting disease-related genes is crucial in disease diagnosis and drug design. The accepted view is that neighbors of a disease-causing gene in a molecular network tend to cause the same or similar diseases, and network-based methods have been recently developed to identify novel hereditary disease-genes in available biomedical networks. Despite the steady increase in the discovery of disease-associated genes, there is still a large fraction of disease genes that remains under the tip of the iceberg. In this paper we exploit the topological properties of the protein-protein interaction (PPI) network to detect disease-related genes. We compute, analyze, and compare the topological properties of disease genes with non-disease genes in PPI networks. We also design an improved random forest classifier based on these network topological features, and a cross-validation test confirms that our method performs better than previous similar studies.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

PubMed

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas ( e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang ). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

PubMed Central

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses. PMID:29403392

Triangle network motifs predict complexes by complementing high-error interactomes with structural information.

PubMed

Andreopoulos, Bill; Winter, Christof; Labudde, Dirk; Schroeder, Michael

2009-06-27

A lot of high-throughput studies produce protein-protein interaction networks (PPINs) with many errors and missing information. Even for genome-wide approaches, there is often a low overlap between PPINs produced by different studies. Second-level neighbors separated by two protein-protein interactions (PPIs) were previously used for predicting protein function and finding complexes in high-error PPINs. We retrieve second level neighbors in PPINs, and complement these with structural domain-domain interactions (SDDIs) representing binding evidence on proteins, forming PPI-SDDI-PPI triangles. We find low overlap between PPINs, SDDIs and known complexes, all well below 10%. We evaluate the overlap of PPI-SDDI-PPI triangles with known complexes from Munich Information center for Protein Sequences (MIPS). PPI-SDDI-PPI triangles have ~20 times higher overlap with MIPS complexes than using second-level neighbors in PPINs without SDDIs. The biological interpretation for triangles is that a SDDI causes two proteins to be observed with common interaction partners in high-throughput experiments. The relatively few SDDIs overlapping with PPINs are part of highly connected SDDI components, and are more likely to be detected in experimental studies. We demonstrate the utility of PPI-SDDI-PPI triangles by reconstructing myosin-actin processes in the nucleus, cytoplasm, and cytoskeleton, which were not obvious in the original PPIN. Using other complementary datatypes in place of SDDIs to form triangles, such as PubMed co-occurrences or threading information, results in a similar ability to find protein complexes. Given high-error PPINs with missing information, triangles of mixed datatypes are a promising direction for finding protein complexes. Integrating PPINs with SDDIs improves finding complexes. Structural SDDIs partially explain the high functional similarity of second-level neighbors in PPINs. We estimate that relatively little structural information would be sufficient for finding complexes involving most of the proteins and interactions in a typical PPIN.

Triangle network motifs predict complexes by complementing high-error interactomes with structural information

PubMed Central

Andreopoulos, Bill; Winter, Christof; Labudde, Dirk; Schroeder, Michael

2009-01-01

Background A lot of high-throughput studies produce protein-protein interaction networks (PPINs) with many errors and missing information. Even for genome-wide approaches, there is often a low overlap between PPINs produced by different studies. Second-level neighbors separated by two protein-protein interactions (PPIs) were previously used for predicting protein function and finding complexes in high-error PPINs. We retrieve second level neighbors in PPINs, and complement these with structural domain-domain interactions (SDDIs) representing binding evidence on proteins, forming PPI-SDDI-PPI triangles. Results We find low overlap between PPINs, SDDIs and known complexes, all well below 10%. We evaluate the overlap of PPI-SDDI-PPI triangles with known complexes from Munich Information center for Protein Sequences (MIPS). PPI-SDDI-PPI triangles have ~20 times higher overlap with MIPS complexes than using second-level neighbors in PPINs without SDDIs. The biological interpretation for triangles is that a SDDI causes two proteins to be observed with common interaction partners in high-throughput experiments. The relatively few SDDIs overlapping with PPINs are part of highly connected SDDI components, and are more likely to be detected in experimental studies. We demonstrate the utility of PPI-SDDI-PPI triangles by reconstructing myosin-actin processes in the nucleus, cytoplasm, and cytoskeleton, which were not obvious in the original PPIN. Using other complementary datatypes in place of SDDIs to form triangles, such as PubMed co-occurrences or threading information, results in a similar ability to find protein complexes. Conclusion Given high-error PPINs with missing information, triangles of mixed datatypes are a promising direction for finding protein complexes. Integrating PPINs with SDDIs improves finding complexes. Structural SDDIs partially explain the high functional similarity of second-level neighbors in PPINs. We estimate that relatively little structural information would be sufficient for finding complexes involving most of the proteins and interactions in a typical PPIN. PMID:19558694

Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation.

PubMed

Li, Jian-Feng; Bush, Jenifer; Xiong, Yan; Li, Lei; McCormack, Matthew

2011-01-01

Protein-protein interactions (PPIs) constitute the regulatory network that coordinates diverse cellular functions. There are growing needs in plant research for creating protein interaction maps behind complex cellular processes and at a systems biology level. However, only a few approaches have been successfully used for large-scale surveys of PPIs in plants, each having advantages and disadvantages. Here we present split firefly luciferase complementation (SFLC) as a highly sensitive and noninvasive technique for in planta PPI investigation. In this assay, the separate halves of a firefly luciferase can come into close proximity and transiently restore its catalytic activity only when their fusion partners, namely the two proteins of interest, interact with each other. This assay was conferred with quantitativeness and high throughput potential when the Arabidopsis mesophyll protoplast system and a microplate luminometer were employed for protein expression and luciferase measurement, respectively. Using the SFLC assay, we could monitor the dynamics of rapamycin-induced and ascomycin-disrupted interaction between Arabidopsis FRB and human FKBP proteins in a near real-time manner. As a proof of concept for large-scale PPI survey, we further applied the SFLC assay to testing 132 binary PPIs among 8 auxin response factors (ARFs) and 12 Aux/IAA proteins from Arabidopsis. Our results demonstrated that the SFLC assay is ideal for in vivo quantitative PPI analysis in plant cells and is particularly powerful for large-scale binary PPI screens.

Low temperature hall effect investigation of conducting polymer-carbon nanotubes composite network.

PubMed

Bahrami, Afarin; Talib, Zainal Abidin; Yunus, Wan Mahmood Mat; Behzad, Kasra; M Abdi, Mahnaz; Din, Fasih Ud

2012-11-14

Polypyrrole (PPy) and polypyrrole-carboxylic functionalized multi wall carbon nanotube composites (PPy/f-MWCNT) were synthesized by in situ chemical oxidative polymerization of pyrrole on the carbon nanotubes (CNTs). The structure of the resulting complex nanotubes was characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The effects of f-MWCNT concentration on the electrical properties of the resulting composites were studied at temperatures between 100 K and 300 K. The Hall mobility and Hall coefficient of PPy and PPy/f-MWCNT composite samples with different concentrations of f-MWCNT were measured using the van der Pauw technique. The mobility decreased slightly with increasing temperature, while the conductivity was dominated by the gradually increasing carrier density.

LocFuse: human protein-protein interaction prediction via classifier fusion using protein localization information.

PubMed

Zahiri, Javad; Mohammad-Noori, Morteza; Ebrahimpour, Reza; Saadat, Samaneh; Bozorgmehr, Joseph H; Goldberg, Tatyana; Masoudi-Nejad, Ali

2014-12-01

Protein-protein interaction (PPI) detection is one of the central goals of functional genomics and systems biology. Knowledge about the nature of PPIs can help fill the widening gap between sequence information and functional annotations. Although experimental methods have produced valuable PPI data, they also suffer from significant limitations. Computational PPI prediction methods have attracted tremendous attentions. Despite considerable efforts, PPI prediction is still in its infancy in complex multicellular organisms such as humans. Here, we propose a novel ensemble learning method, LocFuse, which is useful in human PPI prediction. This method uses eight different genomic and proteomic features along with four types of different classifiers. The prediction performance of this classifier selection method was found to be considerably better than methods employed hitherto. This confirms the complex nature of the PPI prediction problem and also the necessity of using biological information for classifier fusion. The LocFuse is available at: http://lbb.ut.ac.ir/Download/LBBsoft/LocFuse. The results revealed that if we divide proteome space according to the cellular localization of proteins, then the utility of some classifiers in PPI prediction can be improved. Therefore, to predict the interaction for any given protein pair, we can select the most accurate classifier with regard to the cellular localization information. Based on the results, we can say that the importance of different features for PPI prediction varies between differently localized proteins; however in general, our novel features, which were extracted from position-specific scoring matrices (PSSMs), are the most important ones and the Random Forest (RF) classifier performs best in most cases. LocFuse was developed with a user-friendly graphic interface and it is freely available for Linux, Mac OSX and MS Windows operating systems. Copyright © 2014 Elsevier Inc. All rights reserved.

Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bed

PubMed Central

2013-01-01

Background Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H + −rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. Method MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Results Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. Conclusion This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy. PMID:24156349

Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.

PubMed

Ferrari, Stefano; Perut, Francesca; Fagioli, Franca; Brach Del Prever, Adalberto; Meazza, Cristina; Parafioriti, Antonina; Picci, Piero; Gambarotti, Marco; Avnet, Sofia; Baldini, Nicola; Fais, Stefano

2013-10-24

Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H +-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy.

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions

PubMed Central

2014-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. Results We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Conclusions Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies. Reviewers This article was reviewed by Michael Gromiha, Narayanaswamy Srinivasan and Thomas Dandekar. PMID:24708540

Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

PubMed

Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

2015-02-01

To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

Integrative Analysis of GWASs, Human Protein Interaction, and Gene Expression Identified Gene Modules Associated With BMDs

PubMed Central

He, Hao; Zhang, Lei; Li, Jian; Wang, Yu-Ping; Zhang, Ji-Gang; Shen, Jie; Guo, Yan-Fang

2014-01-01

Context: To date, few systems genetics studies in the bone field have been performed. We designed our study from a systems-level perspective by integrating genome-wide association studies (GWASs), human protein-protein interaction (PPI) network, and gene expression to identify gene modules contributing to osteoporosis risk. Methods: First we searched for modules significantly enriched with bone mineral density (BMD)-associated genes in human PPI network by using 2 large meta-analysis GWAS datasets through a dense module search algorithm. One included 7 individual GWAS samples (Meta7). The other was from the Genetic Factors for Osteoporosis Consortium (GEFOS2). One was assigned as a discovery dataset and the other as an evaluation dataset, and vice versa. Results: In total, 42 modules and 129 modules were identified significantly in both Meta7 and GEFOS2 datasets for femoral neck and spine BMD, respectively. There were 3340 modules identified for hip BMD only in Meta7. As candidate modules, they were assessed for the biological relevance to BMD by gene set enrichment analysis in 2 expression profiles generated from circulating monocytes in subjects with low versus high BMD values. Interestingly, there were 2 modules significantly enriched in monocytes from the low BMD group in both gene expression datasets (nominal P value <.05). Two modules had 16 nonredundant genes. Functional enrichment analysis revealed that both modules were enriched for genes involved in Wnt receptor signaling and osteoblast differentiation. Conclusion: We highlighted 2 modules and novel genes playing important roles in the regulation of bone mass, providing important clues for therapeutic approaches for osteoporosis. PMID:25119315

Computational prediction of protein interactions related to the invasion of erythrocytes by malarial parasites.

PubMed

Liu, Xuewu; Huang, Yuxiao; Liang, Jiao; Zhang, Shuai; Li, Yinghui; Wang, Jun; Shen, Yan; Xu, Zhikai; Zhao, Ya

2014-11-30

The invasion of red blood cells (RBCs) by malarial parasites is an essential step in the life cycle of Plasmodium falciparum. Human-parasite surface protein interactions play a critical role in this process. Although several interactions between human and parasite proteins have been discovered, the mechanism related to invasion remains poorly understood because numerous human-parasite protein interactions have not yet been identified. High-throughput screening experiments are not feasible for malarial parasites due to difficulty in expressing the parasite proteins. Here, we performed computational prediction of the PPIs involved in malaria parasite invasion to elucidate the mechanism by which invasion occurs. In this study, an expectation maximization algorithm was used to estimate the probabilities of domain-domain interactions (DDIs). Estimates of DDI probabilities were then used to infer PPI probabilities. We found that our prediction performance was better than that based on the information of D. melanogaster alone when information related to the six species was used. Prediction performance was assessed using protein interaction data from S. cerevisiae, indicating that the predicted results were reliable. We then used the estimates of DDI probabilities to infer interactions between 490 parasite and 3,787 human membrane proteins. A small-scale dataset was used to illustrate the usability of our method in predicting interactions between human and parasite proteins. The positive predictive value (PPV) was lower than that observed in S. cerevisiae. We integrated gene expression data to improve prediction accuracy and to reduce false positives. We identified 80 membrane proteins highly expressed in the schizont stage by fast Fourier transform method. Approximately 221 erythrocyte membrane proteins were identified using published mass spectral datasets. A network consisting of 205 interactions was predicted. Results of network analysis suggest that SNARE proteins of parasites and APP of humans may function in the invasion of RBCs by parasites. We predicted a small-scale PPI network that may be involved in parasite invasion of RBCs by integrating DDI information and expression profiles. Experimental studies should be conducted to validate the predicted interactions. The predicted PPIs help elucidate the mechanism of parasite invasion and provide directions for future experimental investigations.

Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

PubMed Central

Brorsson, C.; Hansen, N. T.; Lage, K.; Bergholdt, R.; Brunak, S.; Pociot, F.

2009-01-01

Aim To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1 genes. Methods We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein–protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein modules were statistically evaluated using permutation. Results A total of 151 genes could be mapped to nodes within the protein interaction network and their interaction partners were identified. Five protein interaction modules reached statistical significance using this approach. The identified proteins are well known in the pathogenesis of T1D, but the modules also contain additional candidates that have been implicated in β-cell development and diabetic complications. Conclusions The extensive LD within the MHC region makes it important to develop new methods for analysing genotyping data for identification of additional risk genes for T1D. Combining genetic data with knowledge about functional pathways provides new insight into mechanisms underlying T1D. PMID:19143816

[Chemical libraries dedicated to protein-protein interactions].

PubMed

Sperandio, Olivier; Villoutreix, Bruno O; Morelli, Xavier; Roche, Philippe

2015-03-01

The identification of complete networks of protein-protein interactions (PPI) within a cell has contributed to major breakthroughs in understanding biological pathways, host-pathogen interactions and cancer development. As a consequence, PPI have emerged as a new class of promising therapeutic targets. However, they are still considered as a challenging class of targets for drug discovery programs. Recent successes have allowed the characterization of structural and physicochemical properties of protein-protein interfaces leading to a better understanding of how they can be disrupted with small molecule compounds. In addition, characterization of the profiles of PPI inhibitors has allowed the development of PPI-focused libraries. In this review, we present the current efforts at developing chemical libraries dedicated to these innovative targets. © 2015 médecine/sciences – Inserm.

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions.

PubMed

Jackson, Rebecca L; Hoffman, Paul; Pobric, Gorana; Lambon Ralph, Matthew A

2016-02-03

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. Copyright © 2016 Jackson et al.

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions

PubMed Central

Jackson, Rebecca L.; Hoffman, Paul; Pobric, Gorana

2016-01-01

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. SIGNIFICANCE STATEMENT Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. PMID:26843633

Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

PubMed

Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

2002-12-01

Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes or cartilage extracts. Both CILP and ANK mRNA expression and ePPi elaboration were stimulated by TGFbeta1 and inhibited by IGF-1 in chondrocytes from all sources. CILP and ANK mRNA expression correlates with chondrocyte ePPi accumulation around CPPD and OA chondrocytes, and all respond similarly to growth factor stimulation. These findings suggest that up-regulated CILP and ANK expression contributes to higher ePPi accumulation from CPPD crystal-forming cartilage.

PPI-IRO: a two-stage method for protein-protein interaction extraction based on interaction relation ontology.

PubMed

Li, Chuan-Xi; Chen, Peng; Wang, Ru-Jing; Wang, Xiu-Jie; Su, Ya-Ru; Li, Jinyan

2014-01-01

Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identification of biological regulatory networks. This paper presents a novel method based on the idea of Interaction Relation Ontology (IRO), which specifies and organises words of various proteins interaction relationships. Our method is a two-stage PPI extraction method. At first, IRO is applied in a binary classifier to determine whether sentences contain a relation or not. Then, IRO is taken to guide PPI extraction by building sentence dependency parse tree. Comprehensive and quantitative evaluations and detailed analyses are used to demonstrate the significant performance of IRO on relation sentences classification and PPI extraction. Our PPI extraction method yielded a recall of around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and BioInfer, respectively, which are superior to most existing extraction methods.

Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

NASA Astrophysics Data System (ADS)

Soni, Namrata; Jain, Keerti; Gupta, Umesh; Jain, N. K.

2015-11-01

The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff's reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC50 value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague-Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI.

Functional connectivity patterns reflect individual differences in conflict adaptation.

PubMed

Wang, Xiangpeng; Wang, Ting; Chen, Zhencai; Hitchman, Glenn; Liu, Yijun; Chen, Antao

2015-04-01

Individuals differ in the ability to utilize previous conflict information to optimize current conflict resolution, which is termed the conflict adaptation effect. Previous studies have linked individual differences in conflict adaptation to distinct brain regions. However, the network-based neural mechanisms subserving the individual differences of the conflict adaptation effect have not been studied. The present study employed a psychophysiological interaction (PPI) analysis with a color-naming Stroop task to examine this issue. The main results were as follows: (1) the anterior cingulate cortex (ACC)-seeded PPI revealed the involvement of the salience network (SN) in conflict adaptation, while the posterior parietal cortex (PPC)-seeded PPI revealed the engagement of the central executive network (CEN). (2) Participants with high conflict adaptation effect showed higher intra-CEN connectivity and lower intra-SN connectivity; while those with low conflict adaptation effect showed higher intra-SN connectivity and lower intra-CEN connectivity. (3) The PPC-centered intra-CEN connectivity positively predicted the conflict adaptation effect; while the ACC-centered intra-SN connectivity had a negative correlation with this effect. In conclusion, our data demonstrated that conflict adaptation is likely supported by the CEN and the SN, providing a new perspective on studying individual differences in conflict adaptation on the basis of large-scale networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Covalent organic framework-derived microporous carbon nanoparticles coated with conducting polypyrrole as an electrochemical capacitor

NASA Astrophysics Data System (ADS)

Kim, Dong Jun; Yoon, Jung Woon; Lee, Chang Soo; Bae, Youn-Sang; Kim, Jong Hak

2018-05-01

We report a high-performance electrochemical capacitor based on covalent organic framework (COF)-derived microporous carbon (MPC) nanoparticles and electrochemically polymerized polypyrrole (Ppy) as a pseudocapacitive material. The COF, Schiff-based network-1 (SNW-1) nanoparticles are prepared via a condensation reaction between melamine and terephthalaldehyde, and the resultant MPC film is prepared via a screen-printing method. The MPC film exhibits a bimodal porous structure with micropores and macropores, resulting in both a large surface area and good electrolyte infiltration. Ppy is synthesized potentio-statically (0.8 V vs. Ag/AgCl) by varying the reaction time, and successful synthesis of Ppy is confirmed via Raman spectroscopy. The specific capacitance with the Ppy coating is enhanced by up to 2.55 F cm-2 due to the synergetic effect of pseudocapacitance and reduced resistance.

Identification of the Inorganic Pyrophosphate Metabolizing, ATP Substituting Pathway in Mammalian Spermatozoa

PubMed Central

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies. PMID:22485177

Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa.

PubMed

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies.

Multichannel Convolutional Neural Network for Biological Relation Extraction.

PubMed

Quan, Chanqin; Hua, Lei; Sun, Xiao; Bai, Wenjun

2016-01-01

The plethora of biomedical relations which are embedded in medical logs (records) demands researchers' attention. Previous theoretical and practical focuses were restricted on traditional machine learning techniques. However, these methods are susceptible to the issues of "vocabulary gap" and data sparseness and the unattainable automation process in feature extraction. To address aforementioned issues, in this work, we propose a multichannel convolutional neural network (MCCNN) for automated biomedical relation extraction. The proposed model has the following two contributions: (1) it enables the fusion of multiple (e.g., five) versions in word embeddings; (2) the need for manual feature engineering can be obviated by automated feature learning with convolutional neural network (CNN). We evaluated our model on two biomedical relation extraction tasks: drug-drug interaction (DDI) extraction and protein-protein interaction (PPI) extraction. For DDI task, our system achieved an overall f -score of 70.2% compared to the standard linear SVM based system (e.g., 67.0%) on DDIExtraction 2013 challenge dataset. And for PPI task, we evaluated our system on Aimed and BioInfer PPI corpus; our system exceeded the state-of-art ensemble SVM system by 2.7% and 5.6% on f -scores.

Characterization of biomarkers in stroke based on ego-networks and pathways.

PubMed

Li, Haixia; Guo, Qianqian

2017-12-01

To explore potential biomarkers in stroke based on ego-networks and pathways. EgoNet method was applied to search for the underlying biomarkers in stroke using transcription profiling of E-GEOD-58294 and protein-protein interaction (PPI) data. Eight ego-genes were identified from PPI network according to the degree characteristics at the criteria of top 5% ranked z-sore and degree >1. Eight candidate ego-networks with classification accuracy ≥0.9 were selected. After performed randomization test, seven significant ego-networks with adjusted p value < 0.05 were identified. Pathway enrichment analysis was then conducted with these ego-networks to search for the significant pathways. Finally, two significant pathways were identified, and six of seven ego-networks were enriched to "3'-UTR-mediated translational regulation" pathway, indicating that this pathway performs an important role in the development of stroke. Seven ego-networks were constructed using EgoNet and two significant enriched by pathways were identified. These may provide new insights into the potential biomarkers for the development of stroke.

A knowledge-driven probabilistic framework for the prediction of protein-protein interaction networks.

PubMed

Browne, Fiona; Wang, Haiying; Zheng, Huiru; Azuaje, Francisco

2010-03-01

This study applied a knowledge-driven data integration framework for the inference of protein-protein interactions (PPI). Evidence from diverse genomic features is integrated using a knowledge-driven Bayesian network (KD-BN). Receiver operating characteristic (ROC) curves may not be the optimal assessment method to evaluate a classifier's performance in PPI prediction as the majority of the area under the curve (AUC) may not represent biologically meaningful results. It may be of benefit to interpret the AUC of a partial ROC curve whereby biologically interesting results are represented. Therefore, the novel application of the assessment method referred to as the partial ROC has been employed in this study to assess predictive performance of PPI predictions along with calculating the True positive/false positive rate and true positive/positive rate. By incorporating domain knowledge into the construction of the KD-BN, we demonstrate improvement in predictive performance compared with previous studies based upon the Naive Bayesian approach. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies

PubMed Central

Brito, Rory C. F.; Guimarães, Frederico G.; Velloso, João P. L.; Corrêa-Oliveira, Rodrigo; Ruiz, Jeronimo C.; Reis, Alexandre B.; Resende, Daniela M.

2017-01-01

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature. The predictions for CD4+ and CD8+ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4+ and T CD8+ epitopes, compared with protective ones. T CD4+ and T CD8+ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism. PMID:28208616

Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies.

PubMed

Brito, Rory C F; Guimarães, Frederico G; Velloso, João P L; Corrêa-Oliveira, Rodrigo; Ruiz, Jeronimo C; Reis, Alexandre B; Resende, Daniela M

2017-02-10

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature. The predictions for CD4⁺ and CD8⁺ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4⁺ and T CD8⁺ epitopes, compared with protective ones. T CD4⁺ and T CD8⁺ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism.

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

PubMed Central

Broderick, Patricia A.; Rosenbaum, Taylor

2013-01-01

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus) although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]). The startle method monitors pre-pulse inhibition (PPI) as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]). Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex. Thus, the data elucidate gender-specificity to the startle response in animals. Finally, preliminary studies show the effect of cocaine on acoustic startle in tandem with effects on estrous cycle. The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein. PMID:24961412

Fabrication and electrochemical properties of carbon nanotube/polypyrrole composite film electrodes with controlled pore size

NASA Astrophysics Data System (ADS)

Kim, Ji-Young; Kim, Kwang Heon; Kim, Kwang Bum

Carbon nanotube (CNT)/polypyrrole (PPy) composites with controlled pore size in a three-dimensional entangled structure of a CNT film are prepared as electrode materials for a pseudocapacitor. A CNT film electrode containing nanosize silica between the CNTs is first fabricated using an electrostatic spray deposition of a mixed suspension of CNTs and nanosize silica on to a platinium-coated silicon wafer. Later, nanosize silica is removed leaving a three-dimensional entangled structure of a CNT film. Before removal of the silica from the CNT/silica film electrode, PPy is electrochemically deposited on to the CNTs to anchor them in their entangled structure. Control of the pore size of the final CNT/PPy composite film can be achieved by changing the amount of silica in the mixed suspension of CNTs and nanosize silica. Nanosize silica acts as a sacrificial filler to change the pore size of the entangled CNT film. Scanning electron microscopy of the electrochemically prepared PPy on the CNT film substrate shows that the PPy nucleated heterogeneously and deposited on the surface of the CNTs. The specific capacitance and rate capability of the CNT/PPy composite electrode with a heavy loading of PPy of around 80 wt.% can be improved when it is made to have a three-dimensional network of entangled CNTs with interconnected pores through pore size control.

An examination of the Psychopathic Personality Inventory's nomological network: a meta-analytic review.

PubMed

Miller, Joshua D; Lynam, Donald R

2012-07-01

Since its publication, the Psychopathic Personality Inventory and its revision (Lilienfeld & Andrews, 1996; Lilienfeld & Widows, 2005) have become increasingly popular such that it is now among the most frequently used self-report inventories for the assessment of psychopathy. The current meta-analysis examined the relations between the two PPI factors (factor 1: Fearless Dominance; factor 2: Self-Centered Impulsivity), as well as their relations with other validated measures of psychopathy, internalizing and externalizing forms of psychopathology, general personality traits, and antisocial personality disorder symptoms. Across 61 samples reported in 49 publications, we found support for the convergent and criterion validity of both PPI factor 2 and the PPI total score. Much weaker validation was found for PPI factor 1, which manifested limited convergent validity and a pattern of correlations with central criterion variables that was inconsistent with many conceptualizations of psychopathy. PsycINFO Database Record (c) 2012 APA, all rights reserved.

The role of TGF-β signaling and apoptosis in innate and adaptive immunity in zebrafish: a systems biology approach.

PubMed

Lin, Che; Lin, Chin-Nan; Wang, Yu-Chao; Liu, Fang-Yu; Chuang, Yung-Jen; Lan, Chung-Yu; Hsieh, Wen-Ping; Chen, Bor-Sen

2014-10-24

The immune system is a key biological system present in vertebrates. Exposure to pathogens elicits various defensive immune mechanisms that protect the host from potential threats and harmful substances derived from pathogens such as parasites, bacteria, and viruses. The complex immune system of humans and many other vertebrates can be divided into two major categories: the innate and the adaptive immune systems. At present, analysis of the complex interactions between the two subsystems that regulate host defense and inflammatory responses remains challenging. Based on time-course microarray data following primary and secondary infection of zebrafish by Candida albicans, we constructed two intracellular protein-protein interaction (PPI) networks for primary and secondary responses of the host. 57 proteins and 341 PPIs were identified for primary infection while 90 proteins and 385 PPIs were identified for secondary infection. There were 20 proteins in common while 37 and 70 proteins specific to primary and secondary infection. By inspecting the hub proteins of each network and comparing significant changes in the number of linkages between the two PPI networks, we identified TGF-β signaling and apoptosis as two of the main functional modules involved in primary and secondary infection. Our initial in silico analyses pave the way for further investigation into the interesting roles played by the TGF-β signaling pathway and apoptosis in innate and adaptive immunity in zebrafish. Such insights could lead to therapeutic advances and improved drug design in the continual battle against infectious diseases.

Making patient and public involvement in cancer and palliative research a reality: academic support is vital for success.

PubMed

Collins, Karen; Boote, Jonathan; Ardron, David; Gath, Jacqui; Green, Tracy; Ahmedzai, Sam H

2015-06-01

Patient and public involvement (PPI) has become an established theme within the UK health research policy and is recognised as an essential force in the drive to improve the quality of services and research. These developments have been particularly rapid in the cancer field. This paper outlines a model of PPI in research (known as the North Trent Cancer Research Network Consumer Research Panel, NTCRN CRP; comprising 38 cancer and palliative care patients/carers) and the key benefits and challenges to effective PPI in cancer research. The PPI model has become a sustainable, inclusive and effective way of implementing PPI within the cancer context. Challenges include (1) a lack of time and funding available to support the PPI model; (2) tensions between different stakeholder groups when developing and conducting health research; (3) panel members finding it difficult to effectively integrate into research meetings when their role and contribution is not made clear at the outset or when unfamiliar language and jargon are used and not explained; (4) some professionals remain unclear about the role and practical implications of PPI in research. However, notwithstanding its financial and organisational challenges, the way that the NTCRN CRP is supported has provided a solid base for it to flourish. PPI provides considerable opportunities for patients and the public to work collaboratively with professionals to influence the cancer research agenda, with the contribution of PPI to the research process being integral to the entire process from the outset, rather than appended to it. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Choice vs. voice? PPI policies and the re-positioning of the state in England and Wales.

PubMed

Hughes, David; Mullen, Caroline; Vincent-Jones, Peter

2009-09-01

CONTEXT AND THESIS: Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re-positioning of the state vis-à-vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Analysis of legislation and official documents, and interviews with policy makers. In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government's policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small-country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply-side market and combine new institutional arrangements for patient 'choice' with other forms of involvement, the Welsh policies focus on 'voice' within a largely publicly-delivered service. While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic.

Competition-cooperation relationship networks characterize the competition and cooperation between proteins

PubMed Central

Li, Hong; Zhou, Yuan; Zhang, Ziding

2015-01-01

By analyzing protein-protein interaction (PPI) networks, one can find that a protein may have multiple binding partners. However, it is difficult to determine whether the interactions with these partners occur simultaneously from binary PPIs alone. Here, we construct the yeast and human competition-cooperation relationship networks (CCRNs) based on protein structural interactomes to clearly exhibit the relationship (competition or cooperation) between two partners of the same protein. If two partners compete for the same interaction interface, they would be connected by a competitive edge; otherwise, they would be connected by a cooperative edge. The properties of three kinds of hubs (i.e., competitive, modest, and cooperative hubs) are analyzed in the CCRNs. Our results show that competitive hubs have higher clustering coefficients and form clusters in the human CCRN, but these tendencies are not observed in the yeast CCRN. We find that the human-specific proteins contribute significantly to these differences. Subsequently, we conduct a series of computational experiments to investigate the regulatory mechanisms that avoid competition between proteins. Our comprehensive analyses reveal that for most yeast and human protein competitors, transcriptional regulation plays an important role. Moreover, the human-specific proteins have a particular preference for other regulatory mechanisms, such as alternative splicing. PMID:26108281

Multifaceted intervention to curb in-hospital over-prescription of proton pump inhibitors: A longitudinal multicenter quasi-experimental before-and-after study.

PubMed

Del Giorno, Rosaria; Ceschi, Alessandro; Pironi, Michela; Zasa, Anna; Greco, Angela; Gabutti, Luca

2018-04-01

Proton pump inhibitors (PPIs) are indicated for a restricted number of clinical conditions, and their misuse can lead to several adverse effects. Despite that, the proportion of overuse is alarmingly high. To test the efficacy of a multifaceted strategy in order to achieve a significant reduction of new PPI prescriptions at discharge in hospitalized patients. Multicenter longitudinal quasi-experimental before-and-after study conducted from July 1st, 2014 to June 30th, 2017. 44,973 admissions in a network of 5 public teaching hospitals of the Italian-speaking region of Switzerland. Multifaceted strategy consisting in a continuous transparent monitoring-benchmarking and in capillary educational interventions applied in the internal medicine departments. To confirm the causality of the results we monitored the trend of new PPI prescriptions in the, not exposed to the intervention, surgery departments of the same hospital network. New PPI prescriptions at hospital discharge. Over the 36month study period 44,973 patient files were analyzed. At admission, comparing internal medicine vs. surgery departments, 44.9% vs. 23.3% of patients were already being treated with a PPI. The annual rate of new PPI prescriptions, for internal medicine showed a decreasing trend: 19, 19, 18, 16% in years 2014, 2015, 2016, 2017, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001), while an increasing rate was found in the surgery departments in the same years: 30, 29, 36, 36%, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001). The case mix was significantly associated with the probability of new PPI prescriptions in both departments (OR1.35, 95% CI 1.26-1.44 for internal medicine and 1.24, 95% CI 1.19-1.30 for surgery). The introduction of a multifaceted intervention significantly reduced the time trend of PPI prescriptions at hospital discharge in internal medicine departments. Further studies are needed to confirm whether the strategy proposed could contribute to optimize the in-hospital drug prescription behavior in other healthcare settings as well. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2).

PubMed

Huan, Jinliang; Wang, Lishan; Xing, Li; Qin, Xianju; Feng, Lingbin; Pan, Xiaofeng; Zhu, Ling

2014-01-01

Estrogens are known to regulate the proliferation of breast cancer cells and to alter their cytoarchitectural and phenotypic properties, but the gene networks and pathways by which estrogenic hormones regulate these events are only partially understood. We used global gene expression profiling by Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI network construction, module analysis and text mining methods to identify patterns and time courses of genes that are either stimulated or inhibited by estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer cells. Of the genes queried on the Affymetrix Human Genome U133 plus 2.0 microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially expressed genes (DEGs) that showed a robust pattern of regulation by E2. From pathway enrichment analysis, we found out the changes of metabolic pathways of E2 treated samples at each time point. At 12h time point, the changes of metabolic pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine signaling pathway. At 24h time point, the changes were mainly enriched in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and calcium signaling pathway. At 48 h time point, the significant pathways were pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network analysis and module analysis found that E2 treatment induced enhancement of PRSS23 at the three time points and PRSS23 was in the central position of each module. Text mining results showed that the important genes of DEGs have relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors (TCF4, MAF). Our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to achieve its widespread effects on breast cancer cells. © 2013 Elsevier B.V. All rights reserved.

LENS: web-based lens for enrichment and network studies of human proteins

PubMed Central

2015-01-01

Background Network analysis is a common approach for the study of genetic view of diseases and biological pathways. Typically, when a set of genes are identified to be of interest in relation to a disease, say through a genome wide association study (GWAS) or a different gene expression study, these genes are typically analyzed in the context of their protein-protein interaction (PPI) networks. Further analysis is carried out to compute the enrichment of known pathways and disease-associations in the network. Having tools for such analysis at the fingertips of biologists without the requirement for computer programming or curation of data would accelerate the characterization of genes of interest. Currently available tools do not integrate network and enrichment analysis and their visualizations, and most of them present results in formats not most conducive to human cognition. Results We developed the tool Lens for Enrichment and Network Studies of human proteins (LENS) that performs network and pathway and diseases enrichment analyses on genes of interest to users. The tool creates a visualization of the network, provides easy to read statistics on network connectivity, and displays Venn diagrams with statistical significance values of the network's association with drugs, diseases, pathways, and GWASs. We used the tool to analyze gene sets related to craniofacial development, autism, and schizophrenia. Conclusion LENS is a web-based tool that does not require and download or plugins to use. The tool is free and does not require login for use, and is available at http://severus.dbmi.pitt.edu/LENS. PMID:26680011

Identifying Dynamic Protein Complexes Based on Gene Expression Profiles and PPI Networks

PubMed Central

Li, Min; Chen, Weijie; Wang, Jianxin; Pan, Yi

2014-01-01

Identification of protein complexes from protein-protein interaction networks has become a key problem for understanding cellular life in postgenomic era. Many computational methods have been proposed for identifying protein complexes. Up to now, the existing computational methods are mostly applied on static PPI networks. However, proteins and their interactions are dynamic in reality. Identifying dynamic protein complexes is more meaningful and challenging. In this paper, a novel algorithm, named DPC, is proposed to identify dynamic protein complexes by integrating PPI data and gene expression profiles. According to Core-Attachment assumption, these proteins which are always active in the molecular cycle are regarded as core proteins. The protein-complex cores are identified from these always active proteins by detecting dense subgraphs. Final protein complexes are extended from the protein-complex cores by adding attachments based on a topological character of “closeness” and dynamic meaning. The protein complexes produced by our algorithm DPC contain two parts: static core expressed in all the molecular cycle and dynamic attachments short-lived. The proposed algorithm DPC was applied on the data of Saccharomyces cerevisiae and the experimental results show that DPC outperforms CMC, MCL, SPICi, HC-PIN, COACH, and Core-Attachment based on the validation of matching with known complexes and hF-measures. PMID:24963481

Reliability and Construct Validity of the Psychopathic Personality Inventory-Revised in a Swedish Non-Criminal Sample - A Multimethod Approach including Psychophysiological Correlates of Empathy for Pain.

PubMed

Sörman, Karolina; Nilsonne, Gustav; Howner, Katarina; Tamm, Sandra; Caman, Shilan; Wang, Hui-Xin; Ingvar, Martin; Edens, John F; Gustavsson, Petter; Lilienfeld, Scott O; Petrovic, Predrag; Fischer, Håkan; Kristiansson, Marianne

2016-01-01

Cross-cultural investigation of psychopathy measures is important for clarifying the nomological network surrounding the psychopathy construct. The Psychopathic Personality Inventory-Revised (PPI-R) is one of the most extensively researched self-report measures of psychopathic traits in adults. To date however, it has been examined primarily in North American criminal or student samples. To address this gap in the literature, we examined PPI-R's reliability, construct validity and factor structure in non-criminal individuals (N = 227) in Sweden, using a multimethod approach including psychophysiological correlates of empathy for pain. PPI-R construct validity was investigated in subgroups of participants by exploring its degree of overlap with (i) the Psychopathy Checklist: Screening Version (PCL:SV), (ii) self-rated empathy and behavioral and physiological responses in an experiment on empathy for pain, and (iii) additional self-report measures of alexithymia and trait anxiety. The PPI-R total score was significantly associated with PCL:SV total and factor scores. The PPI-R Coldheartedness scale demonstrated significant negative associations with all empathy subscales and with rated unpleasantness and skin conductance responses in the empathy experiment. The PPI-R higher order Self-Centered Impulsivity and Fearless Dominance dimensions were associated with trait anxiety in opposite directions (positively and negatively, respectively). Overall, the results demonstrated solid reliability (test-retest and internal consistency) and promising but somewhat mixed construct validity for the Swedish translation of the PPI-R.

Reliability and Construct Validity of the Psychopathic Personality Inventory-Revised in a Swedish Non-Criminal Sample – A Multimethod Approach including Psychophysiological Correlates of Empathy for Pain

PubMed Central

Sörman, Karolina; Nilsonne, Gustav; Howner, Katarina; Tamm, Sandra; Caman, Shilan; Wang, Hui-Xin; Ingvar, Martin; Edens, John F.; Gustavsson, Petter; Lilienfeld, Scott O; Petrovic, Predrag; Fischer, Håkan; Kristiansson, Marianne

2016-01-01

Cross-cultural investigation of psychopathy measures is important for clarifying the nomological network surrounding the psychopathy construct. The Psychopathic Personality Inventory-Revised (PPI-R) is one of the most extensively researched self-report measures of psychopathic traits in adults. To date however, it has been examined primarily in North American criminal or student samples. To address this gap in the literature, we examined PPI-R’s reliability, construct validity and factor structure in non-criminal individuals (N = 227) in Sweden, using a multimethod approach including psychophysiological correlates of empathy for pain. PPI-R construct validity was investigated in subgroups of participants by exploring its degree of overlap with (i) the Psychopathy Checklist: Screening Version (PCL:SV), (ii) self-rated empathy and behavioral and physiological responses in an experiment on empathy for pain, and (iii) additional self-report measures of alexithymia and trait anxiety. The PPI-R total score was significantly associated with PCL:SV total and factor scores. The PPI-R Coldheartedness scale demonstrated significant negative associations with all empathy subscales and with rated unpleasantness and skin conductance responses in the empathy experiment. The PPI-R higher order Self-Centered Impulsivity and Fearless Dominance dimensions were associated with trait anxiety in opposite directions (positively and negatively, respectively). Overall, the results demonstrated solid reliability (test-retest and internal consistency) and promising but somewhat mixed construct validity for the Swedish translation of the PPI-R. PMID:27300292

Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma.

PubMed

Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing

2018-04-23

Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis and benefit the therapy improvement.

Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

PubMed

Hittelman, W N; Broussard, L C; McCredie, K

1979-11-01

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

Proton Pump Inhibitor Use Is Associated With a Reduced Risk of Infection with Intestinal Protozoa.

PubMed

Sheele, Johnathan M

2017-12-01

Proton pump inhibitors (PPIs) can kill some human protozoan parasites in cell culture better than the drug metronidazole. Clinical data showing an antiprotozoal effect for PPIs are lacking. The objective of the study is to determine if PPI use is associated with a reduced risk of having intestinal parasites. We obtained electronic medical record data for all persons who received a stool ova and parasite (O & P) examination at our tertiary care academic medical center in Cleveland, Ohio, between January 2000 and September 2014. We obtained the person's age, whether they were taking a PPI at the time of the O & P examination, and whether the pathology report indicated the presence of any parasites. χ 2 with Yates correction was used to determine if PPI use was associated with stool protozoa. Three intestinal protozoa were identified in 1199 patients taking a PPI (0.3%), and 551 intestinal parasites were identified in the 14,287 patients not taking a PPI (3.9%). There was a statistically significant lower likelihood of finding protozoa in the stool of a person taking a PPI compared with those not taking a PPI (P < .0001). Patients taking a PPI were statistically less likely to have an intestinal protozoa reported on stool O & P examination compared with those not taking a PPI. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Differential reward network functional connectivity in cannabis dependent and non-dependent users☆

PubMed Central

Filbey, Francesca M.; Dunlop, Joseph

2015-01-01

Background Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain’s reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown. Methods In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses. Results PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N = 31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N = 24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas. Conclusions Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies. PMID:24838032

Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.

PubMed

Hu, Wei Qi; Wang, Wei; Fang, Di Long; Yin, Xue Feng

2018-05-24

BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein-protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases. RESULTS A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease-free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets. CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.

Choice vs. voice? PPI policies and the re‐positioning of the state in England and Wales

PubMed Central

Hughes, David; Mullen, Caroline; Vincent‐Jones, Peter

2009-01-01

Abstract Context and Thesis  Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re‐positioning of the state vis‐à‐vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Method  Analysis of legislation and official documents, and interviews with policy makers. Findings  In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government’s policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small‐country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply‐side market and combine new institutional arrangements for patient ‘choice’ with other forms of involvement, the Welsh policies focus on ‘voice’ within a largely publicly‐delivered service. Discussion  While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic. PMID:19754688

Characteristics of children and adolescents first prescribed proton pump inhibitors or histamine-2-receptor antagonists: an observational cohort study.

PubMed

Ruigómez, Ana; Kool-Houweling, Leanne M A; García Rodríguez, Luis A; Penning-van Beest, Fernie J A; Herings, Ron M C

2017-12-01

To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H 2 RAs). Observational studies were conducted using The Health Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0-18 years who were first prescribed a PPI or H 2 RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H 2 RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex. The mean age (years) was higher in the PPI than in the H 2 RA cohorts (THIN 12.3 [n = 8204] vs 5.4 [n = 7937], PHARMO 11.0 [n = 15 362] vs 7.1 [n = 6168]). Previous respiratory disease was more common in the PPI than in the H 2 RA cohort in THIN (OR = 1.19, 95% CI = 1.08-1.30), as were asthma and respiratory medication use in PHARMO (OR = 1.27, 95% CI = 1.12-1.45 and OR = 1.23, 95% CI = 1.10-1.38, respectively) and oral corticosteroid use in both databases (OR = 1.45, 95% CI = 1.10-1.92 [THIN]; OR = 2.80, 95% CI = 2.11-3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H 2 RA cohorts in both databases. Pediatric patients receiving PPIs and those receiving H 2 RAs may represent different patient populations. PPIs may be more commonly prescribed than H 2 RAs among patients with respiratory diseases.

P-Finder: Reconstruction of Signaling Networks from Protein-Protein Interactions and GO Annotations.

PubMed

Young-Rae Cho; Yanan Xin; Speegle, Greg

2015-01-01

Because most complex genetic diseases are caused by defects of cell signaling, illuminating a signaling cascade is essential for understanding their mechanisms. We present three novel computational algorithms to reconstruct signaling networks between a starting protein and an ending protein using genome-wide protein-protein interaction (PPI) networks and gene ontology (GO) annotation data. A signaling network is represented as a directed acyclic graph in a merged form of multiple linear pathways. An advanced semantic similarity metric is applied for weighting PPIs as the preprocessing of all three methods. The first algorithm repeatedly extends the list of nodes based on path frequency towards an ending protein. The second algorithm repeatedly appends edges based on the occurrence of network motifs which indicate the link patterns more frequently appearing in a PPI network than in a random graph. The last algorithm uses the information propagation technique which iteratively updates edge orientations based on the path strength and merges the selected directed edges. Our experimental results demonstrate that the proposed algorithms achieve higher accuracy than previous methods when they are tested on well-studied pathways of S. cerevisiae. Furthermore, we introduce an interactive web application tool, called P-Finder, to visualize reconstructed signaling networks.

Prediction and functional analysis of the sweet orange protein-protein interaction network.

PubMed

Ding, Yu-Duan; Chang, Ji-Wei; Guo, Jing; Chen, Dijun; Li, Sen; Xu, Qiang; Deng, Xiu-Xin; Cheng, Yun-Jiang; Chen, Ling-Ling

2014-08-05

Sweet orange (Citrus sinensis) is one of the most important fruits world-wide. Because it is a woody plant with a long growth cycle, genetic studies of sweet orange are lagging behind those of other species. In this analysis, we employed ortholog identification and domain combination methods to predict the protein-protein interaction (PPI) network for sweet orange. The K-nearest neighbors (KNN) classification method was used to verify and filter the network. The final predicted PPI network, CitrusNet, contained 8,195 proteins with 124,491 interactions. The quality of CitrusNet was evaluated using gene ontology (GO) and Mapman annotations, which confirmed the reliability of the network. In addition, we calculated the expression difference of interacting genes (EDI) in CitrusNet using RNA-seq data from four sweet orange tissues, and also analyzed the EDI distribution and variation in different sub-networks. Gene expression in CitrusNet has significant modular features. Target of rapamycin (TOR) protein served as the central node of the hormone-signaling sub-network. All evidence supported the idea that TOR can integrate various hormone signals and affect plant growth. CitrusNet provides valuable resources for the study of biological functions in sweet orange.

Investigation of candidate genes for osteoarthritis based on gene expression profiles.

PubMed

Dong, Shuanghai; Xia, Tian; Wang, Lei; Zhao, Qinghua; Tian, Jiwei

2016-12-01

To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules. In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs were involved in inflammatory response, while down-regulated DEGs were involved in cell cycle. PPI network with 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle. The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for gene therapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle and cytokine-cytokine receptor interaction pathway. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Effect of graphene oxide on the structural and electrochemical behavior of polypyrrole deposited on cotton fabric

NASA Astrophysics Data System (ADS)

Yaghoubidoust, Fatemeh; Wicaksono, Dedy H. B.; Chandren, Sheela; Nur, Hadi

2014-10-01

Improving the electrical response of polypyrrole-cotton composite is the key issue in making flexible electrode with favorable mechanical strength and large capacitance. Flexible graphene oxide/cotton (GO/Cotton) composite has been prepared by dipping pristine cotton in GO ink. The composite‘s surface was further modified with polypyrrole (Ppy) via chemical polymerization to obtain Ppy/GO/Cotton composite. The composite was characterized using SEM, FTIR and XRD measurements, while the influence of GO in modifying the physicochemical properties of the composite was also examined using TG and cyclic voltammetry. The achieved mean particle size for Ppy/Cotton, Ppy/GO/Cotton and GO estimated using Scherrer formula are 58, 67 and 554 nm, respectively. FTIR spectra revealed prominent fundamental absorption bands in the range of 1400-1800 cm-1. The increased electrical conductivity as much as 2.2 × 10-1 S cm-1 for Ppy/GO/Cotton composite measured by complex impedance, is attributed to the formation of continuous conducting network. The partial reduction of GO on the surface of cotton (GO/Cotton) during chemical polymerization can also affect the conductivity. This simple, economic and environmental-friendly preparation method may contribute towards the controlled growth of quality and stable Ppy/GO/Cotton composites for potential applications in microwave attenuation, energy storage system, static electric charge dissipation and electrotherapy.

Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats.

PubMed

Auclair, Agnès L; Galinier, Alexandra; Besnard, Joël; Newman-Tancredi, Adrian; Depoortère, Ronan

2007-07-01

Prepulse inhibition (PPI) of the startle reflex has been extensively studied because it is disrupted in several psychiatric diseases, most notably schizophrenia. In rats, and to a lesser extent, in humans, PPI can be diminished by dopamine (DA) D(2)/D(3) and serotonin 5-HT(1A) receptor agonists. A novel class of potential antipsychotics (SSR181507, bifeprunox, and SLV313) possess partial agonist/antagonist properties at D(2) receptors and various levels of 5-HT(1A) activation. It thus appeared warranted to assess, in Sprague-Dawley rats, the effects of these antipsychotics on basal PPI. SSR181507, sarizotan, and bifeprunox decreased PPI, with a near-complete abolition at 2.5-10 mg/kg; SLV313 had a significant effect at 0.16 mg/kg only. Co-treatment with the 5-HT(1A) receptor antagonist WAY100,635 (0.63 mg/kg) showed that the 5-HT(1A) agonist activity of SSR181507 was responsible for its effect. By contrast, antipsychotics with low affinity and/or efficacy at 5-HT(1A) receptors, such as aripiprazole (another DA D(2)/D(3) and 5-HT(1A) ligand), and established typical and atypical antipsychotics (haloperidol, clozapine, risperidone, olanzapine, quetiapine, and ziprasidone) had no effect on basal PPI (0.01-2.5 to 2.5-40 mg/kg). The present data demonstrate that some putative antipsychotics with pronounced 5-HT(1A) agonist activity, coupled with partial agonist activity at DA D(2) receptors, markedly diminish PPI of the startle reflex in rats. These data raise the issue of the influence of such compounds on sensorimotor gating in humans.

Single Insulin-Specific CD8+ T Cells Show Characteristic Gene Expression Profiles in Human Type 1 Diabetes

PubMed Central

Luce, Sandrine; Lemonnier, François; Briand, Jean-Paul; Coste, Joel; Lahlou, Najiba; Muller, Sylviane; Larger, Etienne; Rocha, Benedita; Mallone, Roberto; Boitard, Christian

2011-01-01

OBJECTIVE Both the early steps and the high recurrence of autoimmunity once the disease is established are unexplained in human type 1 diabetes. Because CD8+ T cells are central and insulin is a key autoantigen in the disease process, our objective was to characterize HLA class I–restricted autoreactive CD8+ T cells specific for preproinsulin (PPI) in recent-onset and long-standing type 1 diabetic patients and healthy control subjects. RESEARCH DESIGN AND METHODS We used HLA-A*02:01 tetramers complexed to PPI peptides to enumerate circulating PPI-specific CD8+ T cells in patients and characterize them using membrane markers and single-cell PCR. RESULTS Most autoreactive CD8+ T cells detected in recent-onset type 1 diabetic patients are specific for leader sequence peptides, notably PPI6–14, whereas CD8+ T cells in long-standing patients recognize the B-chain peptide PPI33–42 (B9–18). Both CD8+ T-cell specificities are predominantly naïve, central, and effector memory cells, and their gene expression profile differs from cytomegalovirus-specific CD8+ T cells. PPI6–14–specific CD8+ T cells detected in one healthy control displayed Il-10 mRNA expression, which was not observed in diabetic patients. CONCLUSIONS PPI-specific CD8+ T cells in type 1 diabetic patients include central memory and target different epitopes in new-onset versus long-standing disease. Our data support the hypothesis that insulin therapy may contribute to the expansion of autoreactive CD8+ T cells in the long term. PMID:21998398

Network analysis of ChIP-Seq data reveals key genes in prostate cancer.

PubMed

Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Liu, Jianwei; Zheng, Xin; Zhang, Yuhai

2014-09-03

Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC. In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein-protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened. We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and θ polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product (1) and SUMO2 (SMT3 suppressor of mif two 3 homolog (2) . Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.

Determining Effects of Non-synonymous SNPs on Protein-Protein Interactions using Supervised and Semi-supervised Learning

PubMed Central

Zhao, Nan; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

2014-01-01

Single nucleotide polymorphisms (SNPs) are among the most common types of genetic variation in complex genetic disorders. A growing number of studies link the functional role of SNPs with the networks and pathways mediated by the disease-associated genes. For example, many non-synonymous missense SNPs (nsSNPs) have been found near or inside the protein-protein interaction (PPI) interfaces. Determining whether such nsSNP will disrupt or preserve a PPI is a challenging task to address, both experimentally and computationally. Here, we present this task as three related classification problems, and develop a new computational method, called the SNP-IN tool (non-synonymous SNP INteraction effect predictor). Our method predicts the effects of nsSNPs on PPIs, given the interaction's structure. It leverages supervised and semi-supervised feature-based classifiers, including our new Random Forest self-learning protocol. The classifiers are trained based on a dataset of comprehensive mutagenesis studies for 151 PPI complexes, with experimentally determined binding affinities of the mutant and wild-type interactions. Three classification problems were considered: (1) a 2-class problem (strengthening/weakening PPI mutations), (2) another 2-class problem (mutations that disrupt/preserve a PPI), and (3) a 3-class classification (detrimental/neutral/beneficial mutation effects). In total, 11 different supervised and semi-supervised classifiers were trained and assessed resulting in a promising performance, with the weighted f-measure ranging from 0.87 for Problem 1 to 0.70 for the most challenging Problem 3. By integrating prediction results of the 2-class classifiers into the 3-class classifier, we further improved its performance for Problem 3. To demonstrate the utility of SNP-IN tool, it was applied to study the nsSNP-induced rewiring of two disease-centered networks. The accurate and balanced performance of SNP-IN tool makes it readily available to study the rewiring of large-scale protein-protein interaction networks, and can be useful for functional annotation of disease-associated SNPs. SNIP-IN tool is freely accessible as a web-server at http://korkinlab.org/snpintool/. PMID:24784581

Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

PubMed Central

Watanabe, Akiko; Toyota, Tomoko; Owada, Yuji; Hayashi, Takeshi; Iwayama, Yoshimi; Matsumata, Miho; Ishitsuka, Yuichi; Nakaya, Akihiro; Maekawa, Motoko; Ohnishi, Tetsuo; Arai, Ryoichi; Sakurai, Katsuyasu; Yamada, Kazuo; Kondo, Hisatake; Hashimoto, Kenji; Osumi, Noriko; Yoshikawa, Takeo

2007-01-01

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. PMID:18001149

Identification of potential crucial genes associated with steroid-induced necrosis of femoral head based on gene expression profile.

PubMed

Lin, Zhe; Lin, Yongsheng

2017-09-05

The aim of this study was to explore potential crucial genes associated with the steroid-induced necrosis of femoral head (SINFH) and to provide valid biological information for further investigation of SINFH. Gene expression profile of GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using LIMMA package. After functional enrichment analyses of DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted based on the STRING database and cytoscape. In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up-regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and Il7R), and the downregulated DEGs were mainly enriched in muscle system process (e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and 300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based on both subgraph centrality and degree centrality evaluation. These three genes interacted with each other in the network. Furthermore, the significant network module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These genes were mainly enriched in functions like muscle system process. The DEGs related to the regulation of immune system process (e.g. Fcer1A and Il7R), and DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be closely associated with the progress of SINFH, which is still needed to be confirmed by experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring of the molecular mechanism of rhinitis via bioinformatics methods

PubMed Central

Song, Yufen; Yan, Zhaohui

2018-01-01

The aim of this study was to analyze gene expression profiles for exploring the function and regulatory network of differentially expressed genes (DEGs) in pathogenesis of rhinitis by a bioinformatics method. The gene expression profile of GSE43523 was downloaded from the Gene Expression Omnibus database. The dataset contained 7 seasonal allergic rhinitis samples and 5 non-allergic normal samples. DEGs between rhinitis samples and normal samples were identified via the limma package of R. The webGestal database was used to identify enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs. The differentially co-expressed pairs of the DEGs were identified via the DCGL package in R, and the differential co-expression network was constructed based on these pairs. A protein-protein interaction (PPI) network of the DEGs was constructed based on the Search Tool for the Retrieval of Interacting Genes database. A total of 263 DEGs were identified in rhinitis samples compared with normal samples, including 125 downregulated ones and 138 upregulated ones. The DEGs were enriched in 7 KEGG pathways. 308 differential co-expression gene pairs were obtained. A differential co-expression network was constructed, containing 212 nodes. In total, 148 PPI pairs of the DEGs were identified, and a PPI network was constructed based on these pairs. Bioinformatics methods could help us identify significant genes and pathways related to the pathogenesis of rhinitis. Steroid biosynthesis pathway and metabolic pathways might play important roles in the development of allergic rhinitis (AR). Genes such as CDC42 effector protein 5, solute carrier family 39 member A11 and PR/SET domain 10 might be also associated with the pathogenesis of AR, which provided references for the molecular mechanisms of AR. PMID:29257233

Comparison of the effects of omeprazole and rabeprazole on ticlopidine metabolism in vitro.

PubMed

Kinoshita, Yuichi; Matsumoto, Naoki; Watanabe, Minoru; Takeba, Yuko; Yoshida, Yutoku; Ohba, Keiichiro; Suzuki, Satoshi; Itoh, Fumio; Kumai, Toshio; Kobayashi, Shinichi

2011-01-01

The thienopyridine derivative ticlopidine (TCL) is an inhibitor of adenosine diphosphate-induced platelet aggregation. Combination therapy with a thienopyridine derivative and aspirin is standard after coronary stenting, although more hemorrhagic complications occur with the combination therapy than with aspirin alone. A proton pump inhibitor (PPI) is required for prevention or treatment of upper gastrointestinal bleeding in such cases. We examined the effects of PPIs [omeprazole (OPZ) and rabeprazole (RPZ)] on TCL metabolism using pooled human liver microsomes prepared from various human liver blocks and 12 individual human liver microsomes. We calculated the K(i) values of each PPI for TCL metabolic activity and compared the inhibitory effect of each PPI on TCL metabolism. The K(i) values of OPZ and RPZ were 1.4 and 12.7 µM, respectively. The inhibitory effect of OPZ (78.6 ± 0.05%) was significantly greater than that of RPZ (24.2 ± 0.05%) (P < 0.001). Interestingly, a negative correlation existed between the inhibitory effect of OPZ and CYP2C19 activity (r = -0.909, P < 0.001). These results suggest that the inhibitory effect of OPZ is more potent than that of RPZ in vitro. In conclusion, RPZ appears preferable when administering TCL, aspirin, and a PPI in combination.

The Interactomic Analysis Reveals Pathogenic Protein Networks in Phomopsis longicolla Underlying Seed Decay of Soybean.

PubMed

Li, Shuxian; Musungu, Bryan; Lightfoot, David; Ji, Pingsheng

2018-01-01

Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla ) is the primary cause of Phomopsis seed decay (PSD) in soybean, Glycine max (L.) Merrill. This disease results in poor seed quality and is one of the most economically important seed diseases in soybean. The objectives of this study were to infer protein-protein interactions (PPI) and to identify conserved global networks and pathogenicity subnetworks in P. longicolla including orthologous pathways for cell signaling and pathogenesis. The interlog method used in the study identified 215,255 unique PPIs among 3,868 proteins. There were 1,414 pathogenicity related genes in P. longicolla identified using the pathogen host interaction (PHI) database. Additionally, 149 plant cell wall degrading enzymes (PCWDE) were detected. The network captured five different classes of carbohydrate degrading enzymes, including the auxiliary activities, carbohydrate esterases, glycoside hydrolases, glycosyl transferases, and carbohydrate binding molecules. From the PPI analysis, novel interacting partners were determined for each of the PCWDE classes. The most predominant class of PCWDE was a group of 60 glycoside hydrolases proteins. The glycoside hydrolase subnetwork was found to be interacting with 1,442 proteins within the network and was among the largest clusters. The orthologous proteins FUS3, HOG, CYP1, SGE1, and the g5566t.1 gene identified in this study could play an important role in pathogenicity. Therefore, the P. longicolla protein interactome (PiPhom) generated in this study can lead to a better understanding of PPIs in soybean pathogens. Furthermore, the PPI may aid in targeting of genes and proteins for further studies of the pathogenicity mechanisms.

The Interactomic Analysis Reveals Pathogenic Protein Networks in Phomopsis longicolla Underlying Seed Decay of Soybean

PubMed Central

Li, Shuxian; Musungu, Bryan; Lightfoot, David; Ji, Pingsheng

2018-01-01

Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla) is the primary cause of Phomopsis seed decay (PSD) in soybean, Glycine max (L.) Merrill. This disease results in poor seed quality and is one of the most economically important seed diseases in soybean. The objectives of this study were to infer protein–protein interactions (PPI) and to identify conserved global networks and pathogenicity subnetworks in P. longicolla including orthologous pathways for cell signaling and pathogenesis. The interlog method used in the study identified 215,255 unique PPIs among 3,868 proteins. There were 1,414 pathogenicity related genes in P. longicolla identified using the pathogen host interaction (PHI) database. Additionally, 149 plant cell wall degrading enzymes (PCWDE) were detected. The network captured five different classes of carbohydrate degrading enzymes, including the auxiliary activities, carbohydrate esterases, glycoside hydrolases, glycosyl transferases, and carbohydrate binding molecules. From the PPI analysis, novel interacting partners were determined for each of the PCWDE classes. The most predominant class of PCWDE was a group of 60 glycoside hydrolases proteins. The glycoside hydrolase subnetwork was found to be interacting with 1,442 proteins within the network and was among the largest clusters. The orthologous proteins FUS3, HOG, CYP1, SGE1, and the g5566t.1 gene identified in this study could play an important role in pathogenicity. Therefore, the P. longicolla protein interactome (PiPhom) generated in this study can lead to a better understanding of PPIs in soybean pathogens. Furthermore, the PPI may aid in targeting of genes and proteins for further studies of the pathogenicity mechanisms. PMID:29666630

On the integration of protein-protein interaction networks with gene expression and 3D structural data: What can be gained?

NASA Astrophysics Data System (ADS)

Bertolazzi, Paola; Bock, Mary Ellen; Guerra, Concettina; Paci, Paola; Santoni, Daniele

2014-06-01

The biological role of proteins has been analyzed from different perspectives, initially by considering proteins as isolated biological entities, then as cooperating entities that perform their function by interacting with other molecules. There are other dimensions that are important for the complete understanding of the biological processes: time and location. However a protein is rarely annotated with temporal and spatial information. Experimental Protein-Proteins Interaction (PPI) data are static; furthermore they generally do not include transient interactions which are a considerable fraction of the interactome of many organisms. One way to incorporate temporal and condition information is to use other sources of information, such as gene expression data and 3D structural data. Here we review work done to understand the insight that can be gained by enriching PPI data with gene expression and 3D structural data. In particular, we address the following questions: Can the dynamics of a single protein or of an interaction be accurately derived from these data? Can the assembly-disassembly of protein complexes be traced over time? What type of topological changes occur in a PPI network architecture over time?

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

PubMed Central

Swerdlow, Neal R.; Weber, Martin; Qu, Ying; Light, Gregory A.; Braff, David L.

2009-01-01

Introduction Under specific conditions, a weak lead stimulus, or “prepulse”, can inhibit the startling effects of a subsequent intense abrupt stimulus. This startle-inhibiting effect of the prepulse, termed “prepulse inhibition” (PPI), is widely used in translational models to understand the biology of brain based inhibitory mechanisms and their deficiency in neuropsychiatric disorders. In 1981, four published reports with “prepulse inhibition” as an index term were listed on Medline; over the past 5 years, new published Medline reports with “prepulse inhibition” as an index term have appeared at a rate exceeding once every 2.7 days (n = 678). Most of these reports focus on the use of PPI in translational models of impaired sensorimotor gating in schizophrenia. This rapid expansion and broad application of PPI as a tool for understanding schizophrenia has, at times, outpaced critical thinking and falsifiable hypotheses about the relative strengths vs. limitations of this measure. Objectives This review enumerates the realistic expectations for PPI in translational models for schizophrenia research, and provides cautionary notes for the future applications of this important research tool. Conclusion In humans, PPI is not “diagnostic”; levels of PPI do not predict clinical course, specific symptoms, or individual medication responses. In preclinical studies, PPI is valuable for evaluating models or model organisms relevant to schizophrenia, “mapping” neural substrates of deficient PPI in schizophrenia, and advancing the discovery and development of novel therapeutics. Across species, PPI is a reliable, robust quantitative phenotype that is useful for probing the neurobiology and genetics of gating deficits in schizophrenia. PMID:18568339

The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery. | Office of Cancer Genomics

Cancer.gov

Motivation: As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited.

Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods.

PubMed

Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O; Sperandio, Olivier

2010-03-05

Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is freely available on request from our CDithem platform website, www.CDithem.com.

Designing Focused Chemical Libraries Enriched in Protein-Protein Interaction Inhibitors using Machine-Learning Methods

PubMed Central

Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O.; Sperandio, Olivier

2010-01-01

Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is freely available on request from our CDithem platform website, www.CDithem.com. PMID:20221258

Quality improvement of a rice-substituted fried noodle by utilizing the protein-polyphenol interaction between a pea protein isolate and green tea (Camellia sinensis) extract.

PubMed

Song, Youngwoon; Yoo, Sang-Ho

2017-11-15

The quality of rice-substituted fried noodles was improved by applying interaction between pea protein isolate (PPI) and green tea extract (GTE). Radical-scavenging activities of GTE were stably maintained when exposed to acidic pH, UV light, and fluorescent light, but decreased by approximately 65% when exposed to 80°C for 168h. The RVA profiles of noodle dough showed that peak viscosity and breakdown increased significantly but that setback and final viscosity remained unchanged with 20% rice flour replacement. PPI significantly decreased the viscosity parameters of rice-supplemented dough, and the addition of GTE recovered these values significantly. The cooking loss and viscoelasticity (R max ) of cooked rice-supplemented noodles were fully restored by combined treatment of PPI and GTE. GTE decreased the peroxide value of fried noodles by 14% after storage at 63°C for 16days. Therefore, PPI+GTE treatment has great potential for use in fried noodles owing to the reinforced network and antioxidant activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function.

PubMed

Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; Sun, Yuan; You, Qi-Dong

2017-01-01

The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

PubMed Central

Pittenger, Christopher; Adams, Thomas. G.; Gallezot, Jean-Dominique; Crowley, Michael J.; Nabulsi, Nabeel; Ropchan, James; Gao, Hong; Kichuk, Stephen A.; Simpson, Ryan; Billingslea, Eileen; Hannestad, Jonas; Bloch, Michael; Mayes, Linda; Bhagwagar, Zubin; Carson, Richard E.

2016-01-01

Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using 11C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n = 12) and matched healthy controls (HC; n = 12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability (11C-P943 BPND); however, the relationship between PPI and 11C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD. PMID:26919057

Polyethylene-glycol-doped polypyrrole increases the rate performance of the cathode in lithium-sulfur batteries.

PubMed

Wu, Feng; Chen, Junzheng; Li, Li; Zhao, Teng; Liu, Zhen; Chen, Renjie

2013-08-01

Polypyrrole-polyethylene glycol (PPy/PEG)-modified sulfur/aligned carbon nanotubes (PPy/PEG-S/A-CNTs) were synthesized by using an in situ polymerization method. The ratio of PPy to PEG equaled 31.7:1 after polymerization, and the PEG served as a cation dopant in the polymerization and electrochemical reactions. Elemental analysis, FTIR, Raman spectroscopy, XRD, and electrochemical methods were performed to measure the physicochemical properties of the composite. Elemental analysis demonstrated that the sulfur, PPy, PEG, A-CNT, and chloride content in the synthesized material was 64.6%, 22.1%, 0.7%, 12.1%, and 0.5%, respectively. The thickness of the polymer shell was about 15-25 nm, and FTIR confirmed the successful PPy/PEG synthesis. The cathode exhibited a high initial specific capacity of 1355 mAh g(-1) , and a sulfur usage of 81.1%. The reversible capacity of 924 mAh g(-1) was obtained after 100 cycles, showing a remarkably improved cyclability compared to equivalent systems without PEG doping and without any coatings. PPy/PEG provided an effective electronically conductive network and a stable interface structure for the cathode. Rate performance of the PPy/PEG- S/A-CNT composite was more than double that of the unmodified S/A-CNTs. Remarkably, the battery could work at a very high current density of 8 A g(-1) and reached an initial capacity of 542 mAh g(-1) ; it also retained a capacity of 480 mAh g(-1) after 100 cycles. The addition of PEG as a dopant in the PPy shell contributed to this prominent rate improvement. Lithium ions and electrons were available everywhere on the surfaces of the particles, and thus could greatly improve the electrochemical reaction; PEG is a well-known solvent for lithium salts and a very good lithium-ion catcher. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of protein complex from protein-protein interaction network using Markov clustering

NASA Astrophysics Data System (ADS)

Ochieng, P. J.; Kusuma, W. A.; Haryanto, T.

2017-05-01

Detection of complexes, or groups of functionally related proteins, is an important challenge while analysing biological networks. However, existing algorithms to identify protein complexes are insufficient when applied to dense networks of experimentally derived interaction data. Therefore, we introduced a graph clustering method based on Markov clustering algorithm to identify protein complex within highly interconnected protein-protein interaction networks. Protein-protein interaction network was first constructed to develop geometrical network, the network was then partitioned using Markov clustering to detect protein complexes. The interest of the proposed method was illustrated by its application to Human Proteins associated to type II diabetes mellitus. Flow simulation of MCL algorithm was initially performed and topological properties of the resultant network were analysed for detection of the protein complex. The results indicated the proposed method successfully detect an overall of 34 complexes with 11 complexes consisting of overlapping modules and 20 non-overlapping modules. The major complex consisted of 102 proteins and 521 interactions with cluster modularity and density of 0.745 and 0.101 respectively. The comparison analysis revealed MCL out perform AP, MCODE and SCPS algorithms with high clustering coefficient (0.751) network density and modularity index (0.630). This demonstrated MCL was the most reliable and efficient graph clustering algorithm for detection of protein complexes from PPI networks.

A Network Approach to Rare Disease Modeling

NASA Astrophysics Data System (ADS)

Ghiassian, Susan; Rabello, Sabrina; Sharma, Amitabh; Wiest, Olaf; Barabasi, Albert-Laszlo

2011-03-01

Network approaches have been widely used to better understand different areas of natural and social sciences. Network Science had a particularly great impact on the study of biological systems. In this project, using biological networks, candidate drugs as a potential treatment of rare diseases were identified. Developing new drugs for more than 2000 rare diseases (as defined by ORPHANET) is too expensive and beyond expectation. Disease proteins do not function in isolation but in cooperation with other interacting proteins. Research on FDA approved drugs have shown that most of the drugs do not target the disease protein but a protein which is 2 or 3 steps away from the disease protein in the Protein-Protein Interaction (PPI) network. We identified the already known drug targets in the disease gene's PPI subnetwork (up to the 3rd neighborhood) and among them those in the same sub cellular compartment and higher coexpression coefficient with the disease gene are expected to be stronger candidates. Out of 2177 rare diseases, 1092 were found not to have any drug target. Using the above method, we have found the strongest candidates among the rest in order to further experimental validations.

Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

PubMed

Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

2016-06-01

Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

Hub Protein Controversy: Taking a Closer Look at Plant Stress Response Hubs

PubMed Central

Vandereyken, Katy; Van Leene, Jelle; De Coninck, Barbara; Cammue, Bruno P. A.

2018-01-01

Plant stress responses involve numerous changes at the molecular and cellular level and are regulated by highly complex signaling pathways. Studying protein-protein interactions (PPIs) and the resulting networks is therefore becoming increasingly important in understanding these responses. Crucial in PPI networks are the so-called hubs or hub proteins, commonly defined as the most highly connected central proteins in scale-free PPI networks. However, despite their importance, a growing amount of confusion and controversy seems to exist regarding hub protein identification, characterization and classification. In order to highlight these inconsistencies and stimulate further clarification, this review critically analyses the current knowledge on hub proteins in the plant interactome field. We focus on current hub protein definitions, including the properties generally seen as hub-defining, and the challenges and approaches associated with hub protein identification. Furthermore, we give an overview of the most important large-scale plant PPI studies of the last decade that identified hub proteins, pointing out the lack of overlap between different studies. As such, it appears that although major advances are being made in the plant interactome field, defining hub proteins is still heavily dependent on the quality, origin and interpretation of the acquired PPI data. Nevertheless, many hub proteins seem to have a reported role in the plant stress response, including transcription factors, protein kinases and phosphatases, ubiquitin proteasome system related proteins, (co-)chaperones and redox signaling proteins. A significant number of identified plant stress hubs are however still functionally uncharacterized, making them interesting targets for future research. This review clearly shows the ongoing improvements in the plant interactome field but also calls attention to the need for a more comprehensive and precise identification of hub proteins, allowing a more efficient systems biology driven unraveling of complex processes, including those involved in stress responses. PMID:29922309

Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

PubMed

Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

2016-05-01

Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects.

PubMed

Schmid, Yasmin; Enzler, Florian; Gasser, Peter; Grouzmann, Eric; Preller, Katrin H; Vollenweider, Franz X; Brenneisen, Rudolf; Müller, Felix; Borgwardt, Stefan; Liechti, Matthias E

2015-10-15

After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans. In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects. Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed. In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Highly biological active antibiofilm, anticancer and osteoblast adhesion efficacy from MWCNT/PPy/Pd nanocomposite

NASA Astrophysics Data System (ADS)

Murugesan, Balaji; Sonamuthu, Jegatheeswaran; Samayanan, Selvam; Arumugam, Sangili; Mahalingam, Sundrarajan

2018-03-01

Multifunctional biologically active materials have approached for antibiofilm, anticancer and osteoblast adhesion activities with significant biomedical applications, owing to this MWCNT modified with polypyrrole (PPy) matrix with the incorporation of palladium nanoparticles (NPs). The synthesized composite displays a tube-shaped morphology with highly dispersed crystalline Pd NPs, which are established through XRD, SEM, TEM and SAED studies. The pyridinic-N(∼402.7), pyrrolic sbnd N (∼400.8) peak in XPS spectra evidenced the interaction of PPy with Pd and MWCNT. Polymer stretching frequencies in FTIR and Raman spectroscopy proves successful formation of PPy and the Pd-N (1609 cm-1) interaction. In the stability aspect, it is up to 58.73% mass withstood at 800 °C in TGA analysis. The composite exhibits an efficient Anti-biofilm against a set of bacterial stain with planktonic cell growth. In vitro cytotoxicity of Vero and HeLa cell line assess the composites toxicity and anticancer activity up to 100 μg. The outcome of cell adhesions showed that human osteosarcoma cells (HOS) can adhere and to develop on the MWCNT/PPy/Pd composites. Furthermore, the proliferation of cells on MWCNT/PPy/Pd composites was also proved the biocompatibility of the composites against HOS cells. These results suggest that Pd-doped MWCNT/PPy composites are promising materials for biomedical applications.

P³DB 3.0: From plant phosphorylation sites to protein networks.

PubMed

Yao, Qiuming; Ge, Huangyi; Wu, Shangquan; Zhang, Ning; Chen, Wei; Xu, Chunhui; Gao, Jianjiong; Thelen, Jay J; Xu, Dong

2014-01-01

In the past few years, the Plant Protein Phosphorylation Database (P(3)DB, http://p3db.org) has become one of the most significant in vivo data resources for studying plant phosphoproteomics. We have substantially updated P(3)DB with respect to format, new datasets and analytic tools. In the P(3)DB 3.0, there are altogether 47 923 phosphosites in 16 477 phosphoproteins curated across nine plant organisms from 32 studies, which have met our multiple quality standards for acquisition of in vivo phosphorylation site data. Centralized by these phosphorylation data, multiple related data and annotations are provided, including protein-protein interaction (PPI), gene ontology, protein tertiary structures, orthologous sequences, kinase/phosphatase classification and Kinase Client Assay (KiC Assay) data--all of which provides context for the phosphorylation event. In addition, P(3)DB 3.0 incorporates multiple network viewers for the above features, such as PPI network, kinase-substrate network, phosphatase-substrate network, and domain co-occurrence network to help study phosphorylation from a systems point of view. Furthermore, the new P(3)DB reflects a community-based design through which users can share datasets and automate data depository processes for publication purposes. Each of these new features supports the goal of making P(3)DB a comprehensive, systematic and interactive platform for phosphoproteomics research.

Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder.

PubMed

Hassa, Thomas; Sebastian, Alexandra; Liepert, Joachim; Weiller, Cornelius; Schmidt, Roger; Tüscher, Oliver

2017-01-01

Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

NASA Astrophysics Data System (ADS)

Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

2015-03-01

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

Influence of Aripiprazole, Risperidone, and Amisulpride on Sensory and Sensorimotor Gating in Healthy ‘Low and High Gating' Humans and Relation to Psychometry

PubMed Central

Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

2014-01-01

Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making. PMID:24801767

Development and characterization of surface engineered PPI dendrimers for targeted drug delivery.

PubMed

Kaur, Avleen; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

2017-05-01

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA-PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

A variable region within the genome of Streptococcus pneumoniae contributes to strain-strain variation in virulence.

PubMed

Harvey, Richard M; Stroeher, Uwe H; Ogunniyi, Abiodun D; Smith-Vaughan, Heidi C; Leach, Amanda J; Paton, James C

2011-05-05

The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies.

The Role of Specific Alcohol-Related Problems in Predicting Depressive Experiences in a Cross-Sectional National Household Survey.

PubMed

McBride, Orla; Cheng, Hui G; Slade, Tim; Lynskey, Michael T

2016-11-01

This study examines the type of alcohol-related problems that commonly occur before the onset of depressive experiences to shed light on the mechanisms underlying the alcohol-depression comorbidity relationship. Data were from the 1992 USA National Longitudinal Alcohol Epidemiologic Survey. Analytical sample comprised of drinkers with a prior to past year (PPY) history of alcohol-related problems with or without any experiences of depressed mood in the past year (PY). The prevalence of PPY alcohol-related problems was examined, as well as the ability of specific alcohol problems to predict PY experiences of depressed mood. The type of depressed mood experienced by drinkers with PPY history of alcohol-related problems was compared to those without. All but one alcohol-related problem PPY was more frequently endorsed among drinkers with PY experiences of depressed mood. Controlling for confounders, five alcohol-related problems experienced PPY were significantly predictive of depressed mood PY: tolerance, drinking longer than intended, inability to perform important social and occupational roles/obligations, as well as drinking in physically hazardous situations. Drinkers with alcohol-related problems PPY more frequently experienced difficulties with concentration, energy, and thoughts of death, than those without. Alcohol-related problems are likely associated with depressive experiences through a complex network, whereby experiences of physical dependence and negative consequences increase the likelihood of negative affect. Novel study designs are necessary to fully understand the complex mechanisms underlying this comorbidity. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Screening the molecular targets of ovarian cancer based on bioinformatics analysis.

PubMed

Du, Lei; Qian, Xiaolei; Dai, Chenyang; Wang, Lihua; Huang, Ding; Wang, Shuying; Shen, Xiaowei

2015-01-01

Ovarian cancer (OC) is the most lethal gynecologic malignancy. This study aims to explore the molecular mechanisms of OC and identify potential molecular targets for OC treatment. Microarray gene expression data (GSE14407) including 12 normal ovarian surface epithelia samples and 12 OC epithelia samples were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) between 2 kinds of ovarian tissue were identified by using limma package in R language (|log2 fold change| gt;1 and false discovery rate [FDR] lt;0.05). Protein-protein interactions (PPIs) and known OC-related genes were screened from COXPRESdb and GenBank database, respectively. Furthermore, PPI network of top 10 upregulated DEGs and top 10 downregulated DEGs was constructed and visualized through Cytoscape software. Finally, for the genes involved in PPI network, functional enrichment analysis was performed by using DAVID (FDR lt;0.05). In total, 1136 DEGs were identified, including 544 downregulated and 592 upregulated DEGs. Then, PPI network was constructed, and DEGs CDKN2A, MUC1, OGN, ZIC1, SOX17, and TFAP2A interacted with known OC-related genes CDK4, EGFR/JUN, SRC, CLI1, CTNNB1, and TP53, respectively. Moreover, functions about oxygen transport and embryonic development were enriched by the genes involved in the network of downregulated DEGs. We propose that 4 DEGs (OGN, ZIC1, SOX17, and TFAP2A) and 2 functions (oxygen transport and embryonic development) might play a role in the development of OC. These 4 DEGs and known OC-related genes might serve as therapeutic targets for OC. Further studies are required to validate these predictions.

EgoNet: identification of human disease ego-network modules

PubMed Central

2014-01-01

Background Mining novel biomarkers from gene expression profiles for accurate disease classification is challenging due to small sample size and high noise in gene expression measurements. Several studies have proposed integrated analyses of microarray data and protein-protein interaction (PPI) networks to find diagnostic subnetwork markers. However, the neighborhood relationship among network member genes has not been fully considered by those methods, leaving many potential gene markers unidentified. The main idea of this study is to take full advantage of the biological observation that genes associated with the same or similar diseases commonly reside in the same neighborhood of molecular networks. Results We present EgoNet, a novel method based on egocentric network-analysis techniques, to exhaustively search and prioritize disease subnetworks and gene markers from a large-scale biological network. When applied to a triple-negative breast cancer (TNBC) microarray dataset, the top selected modules contain both known gene markers in TNBC and novel candidates, such as RAD51 and DOK1, which play a central role in their respective ego-networks by connecting many differentially expressed genes. Conclusions Our results suggest that EgoNet, which is based on the ego network concept, allows the identification of novel biomarkers and provides a deeper understanding of their roles in complex diseases. PMID:24773628

Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin.

PubMed

Federici, Cristina; Petrucci, Francesco; Caimi, Stefano; Cesolini, Albino; Logozzi, Mariantonia; Borghi, Martina; D'Ilio, Sonia; Lugini, Luana; Violante, Nicola; Azzarito, Tommaso; Majorani, Costanza; Brambilla, Daria; Fais, Stefano

2014-01-01

Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome) release in the resistance of human tumour cell to cisplatin (CisPt); in parallel to proton pump inhibitors (PPI) ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity.

Exosome Release and Low pH Belong to a Framework of Resistance of Human Melanoma Cells to Cisplatin

PubMed Central

Federici, Cristina; Petrucci, Francesco; Caimi, Stefano; Cesolini, Albino; Logozzi, Mariantonia; Borghi, Martina; D'Ilio, Sonia; Lugini, Luana; Violante, Nicola; Azzarito, Tommaso; Majorani, Costanza; Brambilla, Daria; Fais, Stefano

2014-01-01

Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome) release in the resistance of human tumour cell to cisplatin (CisPt); in parallel to proton pump inhibitors (PPI) ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity. PMID:24516610

Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma.

PubMed

Azzarito, Tommaso; Venturi, Giulietta; Cesolini, Albino; Fais, Stefano

2015-01-28

Tumor acidity is now considered an important determinant of drug-resistance and tumor progression, and anti-acidic approaches, such as Proton Pump inhibitors (PPIs), have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to evaluate the possible PPI-induced sensitization of human melanoma cells to Paclitaxel (PTX). Our results show that PTX and the PPI Lansoprazole (LAN) combination was extremely efficient against metastatic melanoma cells, as compared to the single treatments, both in vitro and in vivo. We also showed that acidity plays an important role on the anti-tumor activity of these drugs, being detrimental for PTX activity, while crucial for the synergistic effect of PTX following pretreatment with LAN, due to its nature of pro-drug needing protonation for a full activation. We obtained straightforward results in a human melanoma xenograft model combining well tolerated LAN doses with suboptimal and poorly toxic doses of PTX. With this study we provide a clear evidence that the PPI LAN may be included in new combined therapy of human melanoma together with low doses of PTX. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Silk-polypyrrole biocompatible actuator performance under biologically relevant conditions

NASA Astrophysics Data System (ADS)

Hagler, Jo'elen; Peterson, Ben; Murphy, Amanda; Leger, Janelle

Biocompatible actuators that are capable of controlled movement and can function under biologically relevant conditions are of significant interest in biomedical fields. Previously, we have demonstrated that a composite material of silk biopolymer and the conducting polymer polypyrrole (PPy) can be formed into a bilayer device that can bend under applied voltage. Further, these silk-PPy composites can generate forces comparable to human muscle (>0.1 MPa) making them ideal candidates for interfacing with biological tissues. Here silk-PPy composite films are tested for performance under biologically relevant conditions including exposure to a complex protein serum and biologically relevant temperatures. Free-end bending actuation performance, current response, force generation and, mass degradation were investigated . Preliminary results show that when exposed to proteins and biologically relevant temperatures, these silk-PPy composites show minimal degradation and are able to generate forces and conduct currents comparable to devices tested under standard conditions. NSF.

Viral-templated gold/polypyrrole nanopeapods for an ammonia gas sensor

NASA Astrophysics Data System (ADS)

Yan, Yiran; Zhang, Miluo; Moon, Chung Hee; Su, Heng-Chia; Myung, Nosang V.; Haberer, Elaine D.

2016-08-01

One-dimensional gold/polypyrrole (Au/PPy) nanopeapods were fabricated using a viral template: M13 bacteriophage. The genetically modified filamentous virus displayed gold-binding peptides along its length, allowing selective attachment of gold nanoparticles (Au NPs) under ambient conditions. A PPy shell was electropolymerized on the viral-templated Au NP chains forming nanopeapod structures. The PPy shell morphology and thickness were controlled through electrodeposition potential and time, resulting in an ultra-thin conductive polymer shell of 17.4 ± 3.3 nm. A post-electrodeposition acid treatment was used to modify the electrical properties of these hybrid materials. The electrical resistance of the nanopeapods was monitored at each assembly step. Chemiresistive ammonia (NH3) gas sensors were developed from networks of the hybrid Au/PPy nanostructures. Room temperature sensing performance was evaluated from 5 to 50 ppmv and a mixture of reversible and irreversible chemiresistive behavior was observed. A sensitivity of 0.30%/ppmv was found for NH3 concentrations of 10 ppmv or less, and a lowest detection limit (LDL) of 0.007 ppmv was calculated. Furthermore, acid-treated devices exhibited an enhanced sensitivity of 1.26%/ppmv within the same concentration range and a calculated LDL of 0.005 ppmv.

Microarray and network-based identification of functional modules and pathways of active tuberculosis.

PubMed

Bian, Zhong-Rui; Yin, Juan; Sun, Wen; Lin, Dian-Jie

2017-04-01

Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular mechanism of active TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel dual-functional biosensor for fluorometric detection of inorganic pyrophosphate and pyrophosphatase activity based on globulin stabilized gold nanoclusters.

PubMed

Xu, Shenghao; Feng, Xiuying; Gao, Teng; Wang, Ruizhi; Mao, Yaning; Lin, Jiehua; Yu, Xijuan; Luo, Xiliang

2017-03-15

A novel ultrasensitive dual-functional biosensor for highly sensitive detection of inorganic pyrophosphate (PPi) and pyrophosphatase (PPase) activity was developed based on the fluorescent variation of globulin protected gold nanoclusters (Glo@Au NCs) with the assistance of Cu 2+ . Glo@Au NCs and PPi were used as the fluorescent indicator and substrate for PPase activity evaluation, respectively. In the presence of Cu 2+ , the fluorescence of the Glo@Au NCs will be quenched owing to the formation of Cu 2+ -Glo@Au NCs complex, while PPi can restore the fluorescence of the Cu 2+ -Glo@Au NCs complex because of its higher binding affinity with Cu 2+ . As PPase can catalyze the hydrolysis of PPi, it will lead to the release of Cu 2+ and re-quench the fluorescence of the Glo@Au NCs. Based on this mechanism, quantitative evaluation of the PPi and PPase activity can be achieved ranging from 0.05 μM to 218.125 μM for PPi and from 0.1 to 8 mU for PPase, with detection limits of 0.02 μM and 0.04 mU, respectively, which is much lower than that of other PPi and PPase assay methods. More importantly, this ultrasensitive dual-functional biosensor can also be successfully applied to evaluate the PPase activity in human serum, showing great promise for practical diagnostic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Using Bioinformatics Approach to Explore the Pharmacological Mechanisms of Multiple Ingredients in Shuang-Huang-Lian

PubMed Central

Zhang, Bai-xia; Li, Jian; Gu, Hao; Li, Qiang; Zhang, Qi; Zhang, Tian-jiao; Wang, Yun; Cai, Cheng-ke

2015-01-01

Due to the proved clinical efficacy, Shuang-Huang-Lian (SHL) has developed a variety of dosage forms. However, the in-depth research on targets and pharmacological mechanisms of SHL preparations was scarce. In the presented study, the bioinformatics approaches were adopted to integrate relevant data and biological information. As a result, a PPI network was built and the common topological parameters were characterized. The results suggested that the PPI network of SHL exhibited a scale-free property and modular architecture. The drug target network of SHL was structured with 21 functional modules. According to certain modules and pharmacological effects distribution, an antitumor effect and potential drug targets were predicted. A biological network which contained 26 subnetworks was constructed to elucidate the antipneumonia mechanism of SHL. We also extracted the subnetwork to explicitly display the pathway where one effective component acts on the pneumonia related targets. In conclusions, a bioinformatics approach was established for exploring the drug targets, pharmacological activity distribution, effective components of SHL, and its mechanism of antipneumonia. Above all, we identified the effective components and disclosed the mechanism of SHL from the view of system. PMID:26495421

VANLO - Interactive visual exploration of aligned biological networks

PubMed Central

Brasch, Steffen; Linsen, Lars; Fuellen, Georg

2009-01-01

Background Protein-protein interaction (PPI) is fundamental to many biological processes. In the course of evolution, biological networks such as protein-protein interaction networks have developed. Biological networks of different species can be aligned by finding instances (e.g. proteins) with the same common ancestor in the evolutionary process, so-called orthologs. For a better understanding of the evolution of biological networks, such aligned networks have to be explored. Visualization can play a key role in making the various relationships transparent. Results We present a novel visualization system for aligned biological networks in 3D space that naturally embeds existing 2D layouts. In addition to displaying the intra-network connectivities, we also provide insight into how the individual networks relate to each other by placing aligned entities on top of each other in separate layers. We optimize the layout of the entire alignment graph in a global fashion that takes into account inter- as well as intra-network relationships. The layout algorithm includes a step of merging aligned networks into one graph, laying out the graph with respect to application-specific requirements, splitting the merged graph again into individual networks, and displaying the network alignment in layers. In addition to representing the data in a static way, we also provide different interaction techniques to explore the data with respect to application-specific tasks. Conclusion Our system provides an intuitive global understanding of aligned PPI networks and it allows the investigation of key biological questions. We evaluate our system by applying it to real-world examples documenting how our system can be used to investigate the data with respect to these key questions. Our tool VANLO (Visualization of Aligned Networks with Layout Optimization) can be accessed at . PMID:19821976

Changes in functional connectivity within the fronto-temporal brain network induced by regular and irregular Russian verb production

PubMed Central

Kireev, Maxim; Slioussar, Natalia; Korotkov, Alexander D.; Chernigovskaya, Tatiana V.; Medvedev, Svyatoslav V.

2015-01-01

Functional connectivity between brain areas involved in the processing of complex language forms remains largely unexplored. Contributing to the debate about neural mechanisms underlying regular and irregular inflectional morphology processing in the mental lexicon, we conducted an fMRI experiment in which participants generated forms from different types of Russian verbs and nouns as well as from nonce stimuli. The data were subjected to a whole brain voxel-wise analysis of context dependent changes in functional connectivity [the so-called psychophysiological interaction (PPI) analysis]. Unlike previously reported subtractive results that reveal functional segregation between brain areas, PPI provides complementary information showing how these areas are functionally integrated in a particular task. To date, PPI evidence on inflectional morphology has been scarce and only available for inflectionally impoverished English verbs in a same-different judgment task. Using PPI here in conjunction with a production task in an inflectionally rich language, we found that functional connectivity between the left inferior frontal gyrus (LIFG) and bilateral superior temporal gyri (STG) was significantly greater for regular real verbs than for irregular ones. Furthermore, we observed a significant positive covariance between the number of mistakes in irregular real verb trials and the increase in functional connectivity between the LIFG and the right anterior cingulate cortex in these trails, as compared to regular ones. Our results therefore allow for dissociation between regularity and processing difficulty effects. These results, on the one hand, shed new light on the functional interplay within the LIFG-bilateral STG language-related network and, on the other hand, call for partial reconsideration of some of the previous findings while stressing the role of functional temporo-frontal connectivity in complex morphological processes. PMID:25741262

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

PubMed

Arora, Pradeep; Gupta, Anu; Golzy, Mojgan; Patel, Nilang; Carter, Randolph L; Jalal, Kabir; Lohr, James W

2016-08-03

Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

PubMed

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P < 0.05), the complete bolus transit ( P < 0.01), and the residual pressure of lower esophageal sphincter ( P < 0.05) in these patients. The overall score ( P < 0.01) and the subscale scores of acid reflux syndrome ( P < 0.05), abdominal pain ( P < 0.05), and indigestion syndrome ( P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

Molecular dysexpression in gastric cancer revealed by integrated analysis of transcriptome data.

PubMed

Li, Xiaomei; Dong, Weiwei; Qu, Xueling; Zhao, Huixia; Wang, Shuo; Hao, Yixin; Li, Qiuwen; Zhu, Jianhua; Ye, Min; Xiao, Wenhua

2017-05-01

Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs. Furthermore, a protein-protein interaction (PPI) network of the DEGs was constructed. The expression levels of the DEGs were validated in human GC tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A set of 689 DEGs were identified in GC tissues, as compared with normal tissues, including 202 upregulated DEGs and 487 downregulated DEGs. The KEGG pathway analysis suggested that various pathways may play important roles in the pathology of GC, including pathways related to protein digestion and absorption, extracellular matrix-receptor interaction, and the metabolism of xenobiotics by cytochrome P450. The PPI network analysis indicated that the significant hub proteins consisted of SPP1, TOP2A and ARPC1B. RT-qPCR validation indicated that the expression levels of the top 10 most significantly dysexpressed genes were consistent with the illustration of the integrated analysis. The present study yielded a reference list of reliable DEGs, which represents a robust pool of candidates for further evaluation of GC pathogenesis and treatment.

Regulatory interactions between long noncoding RNA LINC00968 and miR-9-3p in non-small cell lung cancer: A bioinformatic analysis based on miRNA microarray, GEO and TCGA.

PubMed

Li, Dong-Yao; Chen, Wen-Jie; Shang, Jun; Chen, Gang; Li, Shi-Kang

2018-06-01

Long non-coding RNAs (lncRNAs) have been demonstrated to mediate carcinogenesis in various types of cancer. However, the regulatory role of lncRNA LINC00968 in lung adenocarcinoma remains unclear. The microRNA (miRNA) expression in LINC00968-overexpressing human lung adenocarcinoma A549 cells was detected using miRNA microarray analysis. miR-9-3p was selected for further analysis, and its expression was verified in the Gene Expression Omnibus (GEO) database. In addition, the regulatory axis of LINC00968 was validated using The Cancer Genome Atlas (TCGA) database. Results of the GEO database indicated miR-9-3p expression in lung adenocarcinoma was significantly higher compared with normal tissues. Functional enrichment analyses of the target genes of miR-9-3p indicated protein binding and the AMP-activated protein kinase pathway were the most enriched Gene Ontology and KEGG terms, respectively. Combining target genes with the correlated genes of LINC00968 and miR-9-3p, 120 objective genes were obtained, which were used to construct a protein-protein interaction (PPI) network. Cyclin A2 (CCNA2) was identified to have a vital role in the PPI network. Significant correlations were detected between LINC00968, miR-9-3p and CCNA2 in lung adenocarcinoma. The LINC00968/miR-9-3p/CCNA2 regulatory axis provides a new foundation for further evaluating the regulatory mechanisms of LINC00968 in lung adenocarcinoma.

Nitrogen-doped carbon nanofibers derived from polypyrrole coated bacterial cellulose as high-performance electrode materials for supercapacitors and Li-ion batteries

DOE PAGES

Lei, Wen; Han, Lili; Xuan, Cuijuan; ...

2016-05-24

Here, nitrogen-doped carbon nanofiber (NDCN) was synthesized via carbonization of polypyrrole (PPy) coated bacterial cellulose (BC) composites, where BC serves as templates as well as precursor, and PPy serves as the nitrogen source. The synthesized NDCN was employed as electrode for both supercapacitors and Li-ion batteries. The large surface area exposed to electrolyte resulting from the 3D carbon networks leads to sufficient electrode/electrolyte interface and creates shorter transport paths of electrolyte ions and Li + ion. Besides, the three types of N dopants in NDCN improve the electronic conductivity, as well as superior electrochemical performance.

An all-solid-state yarn supercapacitor using cotton yarn electrodes coated with polypyrrole nanotubes.

PubMed

Wei, Chengzhuo; Xu, Qi; Chen, Zeqi; Rao, Weida; Fan, Lingling; Yuan, Ye; Bai, Zikui; Xu, Jie

2017-08-01

A novel all-solid-state yarn supercapacitor (YSC) has been fabricated by using the cotton yarns coated with polypyrrole (PPy) nanotubes. The interconnected network structure of PPy can increase the surface area as well as the electrode/electrolyte interface area, thus resulting in improved electrochemical performance. For the proposed YSC, a high areal-specific capacitance of 74.0mFcm -2 and a desirable energy density of 7.5μWhcm -2 are achieved. The flexibility of the YSC demonstrates that it is suitable for the integration as flexible power sources in wearable electronic textiles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

PubMed Central

Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

2017-01-01

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

Novel electrochemical immune sensor based on Hep-PGA-PPy nanoparticles for detection of α-Fetoprotein in whole blood.

PubMed

Xu, Tingting; Chi, Bo; Gao, Jian; Chu, Meilin; Fan, Wenlu; Yi, Meihui; Xu, Hong; Mao, Chun

2017-07-18

A simple and accurate immune sensor for quantitative detection of α-Fetoprotein (AFP) was developed based on the immobilization of antigen on the surface of Hep-PGA-PPy nanoparticles modified glassy carbon electrodes (GCE). The obtained Hep-PGA-PPy nanoparticles were characterized by fourier transform infrared (FT-IR) spectra and transmission electron microscopy (TEM). And the blood compatibility of Hep-PGA-PPy nanoparticles was investigated by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Combining the conductive property of polypyrrole (PPy) and the biocompatibility of heparin (Hep), the Hep-PGA-PPy nanoparticles could improve not only the anti-biofouling effect the electrode, but also improved the electrochemical properties of the immune sensor. Under optimal conditions, the proposed immune sensor could detect AFP in a linear range from 0.1 to 100 ng mL -1 with a detection limit of 0.099 ng mL -1 at the signal-to-noise ratio of 3, and it also possessed good reproducibility and storage stability. Furthermore, the detection of AFP in five human blood samples also showed satisfactory accuracy with low relative errors. Thus, the developed immune sensor which showed acceptable reproducibility, selectivity, stability and accuracy could be potentially used for the detection of whole blood samples directly. Copyright © 2017. Published by Elsevier B.V.

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine.

PubMed

Pedrazzi, J F C; Issy, A C; Gomes, F V; Guimarães, F S; Del-Bel, E A

2015-08-01

The information processing appears to be deficient in schizophrenia. Prepulse inhibition (PPI), which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents. Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic. Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine. Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor (URB597) in the amphetamine-induced PPI disruption. Male Swiss mice were treated with CBD systemic or intra-accumbens, or URB597 (systemic) prior to amphetamine and were exposed to PPI test. Amphetamine (10 mg/kg) disrupted PPI while CBD (15-60 mg/kg) or URB597 (0.1-1 mg/kg) administered alone had no effect. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration. Similar effects were also found with the inhibitor of anandamide hydrolysis. These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects.

Characterizing biomarkers in osteosarcoma metastasis based on an ego-network.

PubMed

Liu, Zhen; Song, Yan

2017-06-01

To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network. From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway. These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.

Application of Machine Learning Approaches for Protein-protein Interactions Prediction.

PubMed

Zhang, Mengying; Su, Qiang; Lu, Yi; Zhao, Manman; Niu, Bing

2017-01-01

Proteomics endeavors to study the structures, functions and interactions of proteins. Information of the protein-protein interactions (PPIs) helps to improve our knowledge of the functions and the 3D structures of proteins. Thus determining the PPIs is essential for the study of the proteomics. In this review, in order to study the application of machine learning in predicting PPI, some machine learning approaches such as support vector machine (SVM), artificial neural networks (ANNs) and random forest (RF) were selected, and the examples of its applications in PPIs were listed. SVM and RF are two commonly used methods. Nowadays, more researchers predict PPIs by combining more than two methods. This review presents the application of machine learning approaches in predicting PPI. Many examples of success in identification and prediction in the area of PPI prediction have been discussed, and the PPIs research is still in progress. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Self-Supported Crack-Free Conducting Polymer Films with Stabilized Wrinkling Patterns and Their Applications

PubMed Central

Xie, Jixun; Han, Xue; Ji, Haipeng; Wang, Juanjuan; Zhao, Jingxin; Lu, Conghua

2016-01-01

Self-supported conducting polymer films with controlled microarchitectures are highly attractive from fundamental and applied points of view. Here a versatile strategy is demonstrated to fabricate thin free-standing crack-free polyaniline (PANI)-based films with stable wrinkling patterns. It is based on oxidization polymerization of pyrrole inside a pre-wrinkled PANI film, in which the wrinkled PANI film is used both as a template and oxidizing agent for the first time. The subsequently grown polypyrrole (PPy) and the formation of interpenetrated PANI/PPy networks play a decisive role in enhancing the film integrity and the stability of wrinkles. This enhancing effect is attributed to the modification of internal stresses by the interpenetrated PANI/PPy microstructures. Consequently, a crack-free film with stable controlled wrinkles such as the wavelength, orientation and spatial location has been achieved. Moreover, the wrinkling PANI/PPy film can be removed from the initially deposited substrate to become free-standing. It can be further transferred onto target substrates to fabricate hierarchical patterns and functional devices such as flexible electrodes, gas sensors, and surface-enhanced Raman scattering substrates. This simple universal enhancing strategy has been extended to fabrication of other PANI-based composite systems with crack-free film integrity and stabilized surface patterns, irrespective of pattern types and film geometries. PMID:27827459

Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

PubMed Central

Gao, She-Gan; Liu, Rui-Min; Zhao, Yun-Gang; Wang, Pei; Ward, Douglas G.; Wang, Guang-Chao; Guo, Xiang-Qian; Gu, Juan; Niu, Wan-Bin; Zhang, Tian; Martin, Ashley; Guo, Zhi-Peng; Feng, Xiao-Shan; Qi, Yi-Jun; Ma, Yuan-Fang

2016-01-01

Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID:26898710

Identification of key target genes and pathways in laryngeal carcinoma

PubMed Central

Liu, Feng; Du, Jintao; Liu, Jun; Wen, Bei

2016-01-01

The purpose of the present study was to screen the key genes associated with laryngeal carcinoma and to investigate the molecular mechanism of laryngeal carcinoma progression. The gene expression profile of GSE10935 [Gene Expression Omnibus (GEO) accession number], including 12 specimens from laryngeal papillomas and 12 specimens from normal laryngeal epithelia controls, was downloaded from the GEO database. Differentially expressed genes (DEGs) were screened in laryngeal papillomas compared with normal controls using Limma package in R language, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape software and modules were analyzed using MCODE plugin from the PPI network. Furthermore, significant biological pathway regions (sub-pathway) were identified by using iSubpathwayMiner analysis. A total of 67 DEGs were identified, including 27 up-regulated genes and 40 down-regulated genes and they were involved in different GO terms and pathways. PPI network analysis revealed that Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) was a hub protein. The sub-pathway analysis identified 9 significantly enriched sub-pathways, including glycolysis/gluconeogenesis and nitrogen metabolism. Genes such as phosphoglycerate kinase 1 (PGK1), carbonic anhydrase II (CA2), and carbonic anhydrase XII (CA12) whose node degrees were >10 were identified in the disease risk sub-pathway. Genes in the sub-pathway, such as RASSF1, PGK1, CA2 and CA12 were presumed to serve critical roles in laryngeal carcinoma. The present study identified DEGs and their sub-pathways in the disease, which may serve as potential targets for treatment of laryngeal carcinoma. PMID:27446427

Effects of 5-h multimodal stress on the molecules and pathways involved in dendritic morphology and cognitive function.

PubMed

Xu, Yiran; Cheng, Xiaorui; Cui, Xiuliang; Wang, Tongxing; Liu, Gang; Yang, Ruishang; Wang, Jianhui; Bo, Xiaochen; Wang, Shengqi; Zhou, Wenxia; Zhang, Yongxiang

2015-09-01

Stress induces cognitive impairments, which are likely related to the damaged dendritic morphology in the brain. Treatments for stress-induced impairments remain limited because the molecules and pathways underlying these impairments are unknown. Therefore, the aim of this study was to find the potential molecules and pathways related to damage of the dendritic morphology induced by stress. To do this, we detected gene expression, constructed a protein-protein interaction (PPI) network, and analyzed the molecular pathways in the brains of mice exposed to 5-h multimodal stress. The results showed that stress increased plasma corticosterone concentration, decreased cognitive function, damaged dendritic morphologies, and altered APBB1, CLSTN1, KCNA4, NOTCH3, PLAU, RPS6KA1, SYP, TGFB1, KCNA1, NTRK3, and SNCA expression in the brains of mice. Further analyses found that the abnormal expressions of CLSTN1, PLAU, NOTCH3, and TGFB1 induced by stress were related to alterations in the dendritic morphology. These four genes demonstrated interactions with 55 other genes, and configured a closed PPI network. Molecular pathway analysis use the Database for Annotation, Visualization, and Integrated Discovery (DAVID), specifically the gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG), each identified three pathways that were significantly enriched in the gene list of the PPI network, with genes belonging to the Notch and transforming growth factor-beta (TGF-B) signaling pathways being the most enriched. Our results suggest that TGFB1, PLAU, NOTCH3, and CLSTN1 may be related to the alterations in dendritic morphology induced by stress, and imply that the Notch and TGF-B signaling pathways may be involved. Copyright © 2015 Elsevier Inc. All rights reserved.

A Versatile Nanowire Platform for Highly Efficient Isolation and Direct PCR-free Colorimetric Detection of Human Papillomavirus DNA from Unprocessed Urine

PubMed Central

Lee, HyungJae; Choi, Mihye; Hwang, Sang-Hyun; Cho, Youngnam

2018-01-01

Purpose: As human papillomavirus (HPV) is primarily responsible for the development of cervical cancer, significant efforts have been devoted to develop novel strategies for detecting and identifying HPV DNA in urine. The analysis of target DNA sequences in urine offers a potential alternative to conventional methods as a non-invasive clinical screening and diagnostic assessment tool for the detection of HPV. However, the lack of efficient approaches to isolate and directly detect HPV DNA in urine has restricted its potential clinical use. In this study, we demonstrated a novel approach of using polyethylenimine-conjugated magnetic polypyrrole nanowires (PEI-mPpy NWs) for the extraction, identification, and PCR-free colorimetric detection of high-risk strains of HPV DNA sequences, particularly HPV-16 and HPV-18, in urine specimens of cervical cancer patients. Materials and Methods: We fabricated and characterized polyethylenimine-conjugated magnetic nanowires (PEI/mPpy NWs). PEI/mPpy NWs-based HPV DNA isolation and detection strategy appears to be a cost-effective and practical technology with greater sensitivity and accuracy than other urine-based methods. Results: The analytical and clinical performance of PEI-mPpy NWs was evaluated and compared with those of cervical swabs, demonstrating a superior type-specific concordance rate of 100% between urine and cervical swabs, even when using a small volume of urine (300 µL). Conclusion: We envision that PEI-mPpy NWs provide substantive evidence for clinical diagnosis and management of HPV-associated disease with their excellent performance in the recovery and detection of HPV DNA from minimal amounts of urine samples. PMID:29290816

Polyurethane nanofiber strain sensors via in situ polymerization of polypyrrole and application to monitoring joint flexion

NASA Astrophysics Data System (ADS)

Kim, Inhwan; Cho, Gilsoo

2018-07-01

Strain sensors made of intrinsically conductive polymers (ICPs) and nanofibers were fabricated and tested for suitability for use in wearable technology. The sensors were fabricated and evaluated based on their surface appearances, and electrical, tensile, and chemical/thermal properties. Polypyrrole (PPy) was in situ polymerized onto polyurethane (PU) nanofiber substrates by exposing pyrrole monomers to ammonium persulfate as oxidant and 2,6-naphthalenedisulfonic acid disodium salt as doping agents in an aqueous bath. The PPy treated PU nanofibers were then coated with polydimethylsiloxane (PDMS). Both pyrrole concentrations and layer numbers were significantly related to change in electrical conductivity. Specimen treated with 0.1 M of PPy and having three layered structure showed the best electrical conductivity. Regarding tensile strength, the in situ polymerization process decreased tensile strength because the oxidant chemically degraded the PU fibers. Adding layers and PDMS treatment generally improved tensile properties while adding layers created fracture parts in the stress–strain curves. The treatment condition of 0.1 M of PPy, two layered, and PDMS treated specimen showed the best tensile properties as a strain sensor. The chemical property evaluation with Fourier transform infrared and x-ray photoelectron spectroscopy tests showed successful PPy polymerization and PDMS treatments. The functional groups and chemical bonds in polyol, urethane linkage, backbone ring structure in PPy, silicon-based functional groups in PDMS, and elemental content changes by treatment at each stage were characterized. The real-time data acquired from the dummy and five human subjects with repetition of motion at three different speeds of 0.16, 0.25 and 0.5 Hz generated similar trends and tendencies. The PU nanofiber sensors based on PPy and PDMS treatments in this study point to the possibility of developing textiles based wearable strain sensors developed using ICPs.

Natural products used as a chemical library for protein-protein interaction targeted drug discovery.

PubMed

Jin, Xuemei; Lee, Kyungro; Kim, Nam Hee; Kim, Hyun Sil; Yook, Jong In; Choi, Jiwon; No, Kyoung Tai

2018-01-01

Protein-protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an in vitro experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrodeposition of zinc hydroxysulfate nanosheets and reduction to zinc metal microdendrites on polypyrrole films.

PubMed

Andreoli, Enrico; Rooney, Denise A; Redington, Wynette; Gunning, Robert; Breslin, Carmel B

2012-01-01

Nanothin sheets made of zinc sulfate hydroxide hydrate, ZnSO4[Zn(OH)2]3 x 5H2O, are easily and quickly prepared using an innovative electrochemical route onto polypyrrole-polystyrene sulfonate (PPy-PSS) films. The sheets are characterized using a range of experimental techniques. The deposits are formed on the film surface with instantaneous nucleation to grow into a network of entangled nanosheets. The effect of the experimental conditions on the deposition is reported. Interestingly, the formation of the nanosheets is observed on PPy-PSS films only, and not on films doped with other sulfate/sulfonate dopants. The zinc nanosheets can be easily electrochemically reduced to metallic zinc microdentrites.

De Novo Synthesis and Functional Analysis of Polyphosphate-Loaded Poly(Ethylene) Glycol Hydrogel Nanoparticles Targeting Pyocyanin and Pyoverdin Production in Pseudomonas aeruginosa as a Model Intestinal Pathogen

PubMed Central

Yin, Yushu; Papavasiliou, Georgia; Zaborina, Olga Y.; Alverdy, John C.; Teymour, Fouad

2017-01-01

The human gastrointestinal tract is the primary site of colonization of multidrug resistant pathogens and the major source of life-threatening complications in critically ill and immunocompromised patients. Eradication measures using antibiotics carry further risk of antibiotic resistance. Furthermore, antibiotic treatment can adversely shift the intestinal microbiome toward domination by resistant pathogens. Therefore, approaches directed to prevent replacement of health promoting microbiota with resistant pathogens should be developed. The use of non-microbicidal drugs to create microenvironmental conditions that suppress virulence of pathogens is an attractive strategy to minimize the negative consequences of intestinal microbiome disruption. We have previously shown that phosphate is depleted in the intestinal tract following surgical injury, that this depletion is a major “cue” that triggers bacterial virulence, and that the maintenance of phosphate abundance prevents virulence expression. However, the use of inorganic phosphate may not be a suitable agent to deliver to the site of the host-pathogen interaction since it is readily adsorbed in small intestine. Here we propose a novel drug delivery approach that exploits the use of nanoparticles that allow for prolonged release of phosphates. We have synthesized phosphate (Pi) and polyphosphate (PPi) crosslinked poly (ethylene) glycol (PEG) hydrogel nanoparticles (NP-Pi and NP-PPi, respectively) that result in sustained delivery of Pi and PPi. NP-PPi demonstrated more prolonged release of PPi as compared to the release of Pi from NP-Pi. In vitro studies indicate that free PPi as well NP-PPi are effective compounds for suppressing pyoverdin and pyocyanin production, two global virulence systems of virulence of P. aeruginosa. These studies suggest that sustained release of polyphosphate from NP-PPi can be exploited as a target for virulence suppression of lethal pathogenic phenotypes in the gastrointestinal tract. PMID:27761766

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

PubMed Central

Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice.

PubMed

Pomozi, Viola; Brampton, Christopher; van de Wetering, Koen; Zoll, Janna; Calio, Bianca; Pham, Kevin; Owens, Jesse B; Marh, Joel; Moisyadi, Stefan; Váradi, András; Martin, Ludovic; Bauer, Carolin; Erdmann, Jeanette; Aherrahrou, Zouhair; Le Saux, Olivier

2017-06-01

Soft tissue calcification occurs in several common acquired pathologies, such as diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a transmembrane transporter primarily expressed in liver and kidneys, initiates a molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a major calcification inhibitor. Heritable mutations in ABCC6 underlie the incurable calcification disorder pseudoxanthoma elasticum and some cases of generalized arterial calcification of infancy. Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6 -/- mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. We also found that daily injection of PPi to Abcc6 -/- mice over several months prevented the development of pseudoxanthoma elasticum-like spontaneous calcification, but failed to reverse already established lesions. Furthermore, we found that the expression of low amounts of the human ABCC6 in liver of transgenic Abcc6 -/- mice, resulting in only a 27% increase in plasma PPi levels, led to a major reduction in acute and chronic calcification phenotypes. This proof-of-concept study shows that the development of both acute and chronic calcification associated with ABCC6 deficiency can be prevented by compensating PPi deficits, even partially. Our work indicates that PPi substitution represents a promising strategy to treat ABCC6-dependent calcification disorders. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Helplessness and perceived pain intensity: relations to cortisol concentrations after electrocutaneous stimulation in healthy young men

PubMed Central

2011-01-01

Background Uncontrollable aversive events are associated with feelings of helplessness and cortisol elevation and are suitable as a model of depression. The high comorbidity of depression and pain symptoms and the importance of controllability in both conditions are clinically well-known but empirical studies are scarce. The study investigated the relationship of pain experience, helplessness, and cortisol secretion after controllable vs. uncontrollable electric skin stimulation in healthy male individuals. Methods Sixty-four male volunteers were randomly assigned to receive 30 controllable (self-administered) or uncontrollable (experimenter-administered) painful electric skin stimuli. Perceived pain intensity (PPI), subjective helplessness ratings, and salivary cortisol concentrations were assessed. PPI was assessed after stress exposure. For salivary cortisol concentrations and subjective helplessness ratings, areas under the response curve (AUC) were calculated. Results After uncontrollable vs. controllable stress exposure significantly higher PPI ratings (P = 0.023), higher subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P = 0.004, t-tests) were found. Correlation analyses revealed a significant correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005), subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and between PPI and salivary cortisol AUC (r = 0.298, P = 0.017). Conclusions The results confirm the impact of uncontrollability on stress responses in humans; the relationship of PPI with subjective helplessness and salivary cortisol suggests a cognitive-affective sensitization of pain perception, particularly under uncontrollable conditions. PMID:21718526

A Novel Algorithm for Detecting Protein Complexes with the Breadth First Search

PubMed Central

Tang, Xiwei; Wang, Jianxin; Li, Min; He, Yiming; Pan, Yi

2014-01-01

Most biological processes are carried out by protein complexes. A substantial number of false positives of the protein-protein interaction (PPI) data can compromise the utility of the datasets for complexes reconstruction. In order to reduce the impact of such discrepancies, a number of data integration and affinity scoring schemes have been devised. The methods encode the reliabilities (confidence) of physical interactions between pairs of proteins. The challenge now is to identify novel and meaningful protein complexes from the weighted PPI network. To address this problem, a novel protein complex mining algorithm ClusterBFS (Cluster with Breadth-First Search) is proposed. Based on the weighted density, ClusterBFS detects protein complexes of the weighted network by the breadth first search algorithm, which originates from a given seed protein used as starting-point. The experimental results show that ClusterBFS performs significantly better than the other computational approaches in terms of the identification of protein complexes. PMID:24818139

Cellulose-coupled graphene/polypyrrole composite electrodes containing conducting networks built by carbon fibers as wearable supercapacitors with excellent foldability and tailorability

NASA Astrophysics Data System (ADS)

Lyu, Shaoyi; Chang, Huanjun; Fu, Feng; Hu, La; Huang, Jingda; Wang, Siqun

2016-09-01

A paper-based wearable supercapacitor with excellent foldability and tailorability is fabricated from a chopped carbon fiber (CCF)-reinforced cellulose paper electrode material by coating with reduced graphene oxide (RGO) and polypyrrole (PPy) via in situ polymerization. The CCFs not only form an interpenetrating conducting network that acts as highly conductive electron transfer highways for the RGO/PPy layer in the paper electrode, but also endow the resulting electrode with an excellent areal capacitance of 363 mF cm-2 and a volumetric energy density of 0.28 mW h cm-3. Further, the CCFs give the electrode remarkable mechanical robustness, guaranteeing foldability and tailorability, with only slight loss of capacitance after repeated folding 600 times. Even after being subjected to severe cut-in fracture, the capacitance retention is up to 84%, indicating outstanding damage tolerance. The present study reveals a promising candidate for flexible wearable energy storage devices that are required to function in harsh environments.

Systematic analysis of molecular mechanisms for HCC metastasis via text mining approach.

PubMed

Zhen, Cheng; Zhu, Caizhong; Chen, Haoyang; Xiong, Yiru; Tan, Junyuan; Chen, Dong; Li, Jin

2017-02-21

To systematically explore the molecular mechanism for hepatocellular carcinoma (HCC) metastasis and identify regulatory genes with text mining methods. Genes with highest frequencies and significant pathways related to HCC metastasis were listed. A handful of proteins such as EGFR, MDM2, TP53 and APP, were identified as hub nodes in PPI (protein-protein interaction) network. Compared with unique genes for HBV-HCCs, genes particular to HCV-HCCs were less, but may participate in more extensive signaling processes. VEGFA, PI3KCA, MAPK1, MMP9 and other genes may play important roles in multiple phenotypes of metastasis. Genes in abstracts of HCC-metastasis literatures were identified. Word frequency analysis, KEGG pathway and PPI network analysis were performed. Then co-occurrence analysis between genes and metastasis-related phenotypes were carried out. Text mining is effective for revealing potential regulators or pathways, but the purpose of it should be specific, and the combination of various methods will be more useful.

Network methods to support user involvement in qualitative data analyses: an introduction to Participatory Theme Elicitation.

PubMed

Best, Paul; Badham, Jennifer; Corepal, Rekesh; O'Neill, Roisin F; Tully, Mark A; Kee, Frank; Hunter, Ruth F

2017-11-23

While Patient and Public Involvement (PPI) is encouraged throughout the research process, engagement is typically limited to intervention design and post-analysis stages. There are few approaches to participatory data analyses within complex health interventions. Using qualitative data from a feasibility randomised controlled trial (RCT), this proof-of-concept study tests the value of a new approach to participatory data analysis called Participatory Theme Elicitation (PTE). Forty excerpts were given to eight members of a youth advisory PPI panel to sort into piles based on their perception of related thematic content. Using algorithms to detect communities in networks, excerpts were then assigned to a thematic cluster that combined the panel members' perspectives. Network analysis techniques were also used to identify key excerpts in each grouping that were then further explored qualitatively. While PTE analysis was, for the most part, consistent with the researcher-led analysis, young people also identified new emerging thematic content. PTE appears promising for encouraging user led identification of themes arising from qualitative data collected during complex interventions. Further work is required to validate and extend this method. ClinicalTrials.gov, ID: NCT02455986 . Retrospectively Registered on 21 May 2015.

Construction of phosphorylation interaction networks by text mining of full-length articles using the eFIP system.

PubMed

Tudor, Catalina O; Ross, Karen E; Li, Gang; Vijay-Shanker, K; Wu, Cathy H; Arighi, Cecilia N

2015-01-01

Protein phosphorylation is a reversible post-translational modification where a protein kinase adds a phosphate group to a protein, potentially regulating its function, localization and/or activity. Phosphorylation can affect protein-protein interactions (PPIs), abolishing interaction with previous binding partners or enabling new interactions. Extracting phosphorylation information coupled with PPI information from the scientific literature will facilitate the creation of phosphorylation interaction networks of kinases, substrates and interacting partners, toward knowledge discovery of functional outcomes of protein phosphorylation. Increasingly, PPI databases are interested in capturing the phosphorylation state of interacting partners. We have previously developed the eFIP (Extracting Functional Impact of Phosphorylation) text mining system, which identifies phosphorylated proteins and phosphorylation-dependent PPIs. In this work, we present several enhancements for the eFIP system: (i) text mining for full-length articles from the PubMed Central open-access collection; (ii) the integration of the RLIMS-P 2.0 system for the extraction of phosphorylation events with kinase, substrate and site information; (iii) the extension of the PPI module with new trigger words/phrases describing interactions and (iv) the addition of the iSimp tool for sentence simplification to aid in the matching of syntactic patterns. We enhance the website functionality to: (i) support searches based on protein roles (kinases, substrates, interacting partners) or using keywords; (ii) link protein entities to their corresponding UniProt identifiers if mapped and (iii) support visual exploration of phosphorylation interaction networks using Cytoscape. The evaluation of eFIP on full-length articles achieved 92.4% precision, 76.5% recall and 83.7% F-measure on 100 article sections. To demonstrate eFIP for knowledge extraction and discovery, we constructed phosphorylation-dependent interaction networks involving 14-3-3 proteins identified from cancer-related versus diabetes-related articles. Comparison of the phosphorylation interaction network of kinases, phosphoproteins and interactants obtained from eFIP searches, along with enrichment analysis of the protein set, revealed several shared interactions, highlighting common pathways discussed in the context of both diseases. © The Author(s) 2015. Published by Oxford University Press.

A rationale for the use of proton pump inhibitors as antineoplastic agents.

PubMed

De Milito, Angelo; Marino, Maria Lucia; Fais, Stefano

2012-01-01

It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic acid and protons, otherwise detrimental to cell survival is crucial for malignant cells to maintain cellular pH homeostasis. As a consequence of the upregulated expression and/or function of several pH-regulating systems, cancer cells display an alkaline intracellular pH (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins, proton pumps play an important role in both drug-resistance and metastatic spread, thus representing a suitable therapeutic target. Proton pump inhibitors (PPI) have been reported as cytotoxic drugs active against several human tumor cells and preclinical data have prompted the investigation of PPI as anticancer agents in humans. This review will update the current knowledge on the antitumor activities of PPI and their potential applications.

PPInterFinder--a mining tool for extracting causal relations on human proteins from literature.

PubMed

Raja, Kalpana; Subramani, Suresh; Natarajan, Jeyakumar

2013-01-01

One of the most common and challenging problem in biomedical text mining is to mine protein-protein interactions (PPIs) from MEDLINE abstracts and full-text research articles because PPIs play a major role in understanding the various biological processes and the impact of proteins in diseases. We implemented, PPInterFinder--a web-based text mining tool to extract human PPIs from biomedical literature. PPInterFinder uses relation keyword co-occurrences with protein names to extract information on PPIs from MEDLINE abstracts and consists of three phases. First, it identifies the relation keyword using a parser with Tregex and a relation keyword dictionary. Next, it automatically identifies the candidate PPI pairs with a set of rules related to PPI recognition. Finally, it extracts the relations by matching the sentence with a set of 11 specific patterns based on the syntactic nature of PPI pair. We find that PPInterFinder is capable of predicting PPIs with the accuracy of 66.05% on AIMED corpus and outperforms most of the existing systems. DATABASE URL: http://www.biomining-bu.in/ppinterfinder/

PPInterFinder—a mining tool for extracting causal relations on human proteins from literature

PubMed Central

Raja, Kalpana; Subramani, Suresh; Natarajan, Jeyakumar

2013-01-01

One of the most common and challenging problem in biomedical text mining is to mine protein–protein interactions (PPIs) from MEDLINE abstracts and full-text research articles because PPIs play a major role in understanding the various biological processes and the impact of proteins in diseases. We implemented, PPInterFinder—a web-based text mining tool to extract human PPIs from biomedical literature. PPInterFinder uses relation keyword co-occurrences with protein names to extract information on PPIs from MEDLINE abstracts and consists of three phases. First, it identifies the relation keyword using a parser with Tregex and a relation keyword dictionary. Next, it automatically identifies the candidate PPI pairs with a set of rules related to PPI recognition. Finally, it extracts the relations by matching the sentence with a set of 11 specific patterns based on the syntactic nature of PPI pair. We find that PPInterFinder is capable of predicting PPIs with the accuracy of 66.05% on AIMED corpus and outperforms most of the existing systems. Database URL: http://www.biomining-bu.in/ppinterfinder/ PMID:23325628

Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

PubMed

Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

2016-01-01

Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

Analysis of gene expression profile microarray data in complex regional pain syndrome.

PubMed

Tan, Wulin; Song, Yiyan; Mo, Chengqiang; Jiang, Shuangjian; Wang, Zhongxing

2017-09-01

The aim of the present study was to predict key genes and proteins associated with complex regional pain syndrome (CRPS) using bioinformatics analysis. The gene expression profiling microarray data, GSE47603, which included peripheral blood samples from 4 patients with CRPS and 5 healthy controls, was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in CRPS patients compared with healthy controls were identified using the GEO2R online tool. Functional enrichment analysis was then performed using The Database for Annotation Visualization and Integrated Discovery online tool. Protein‑protein interaction (PPI) network analysis was subsequently performed using Search Tool for the Retrieval of Interaction Genes database and analyzed with Cytoscape software. A total of 257 DEGs were identified, including 243 upregulated genes and 14 downregulated ones. Genes in the human leukocyte antigen (HLA) family were most significantly differentially expressed. Enrichment analysis demonstrated that signaling pathways, including immune response, cell motion, adhesion and angiogenesis were associated with CRPS. PPI network analysis revealed that key genes, including early region 1A binding protein p300 (EP300), CREB‑binding protein (CREBBP), signal transducer and activator of transcription (STAT)3, STAT5A and integrin α M were associated with CRPS. The results suggest that the immune response may therefore serve an important role in CRPS development. In addition, genes in the HLA family, such as HLA‑DQB1 and HLA‑DRB1, may present potential biomarkers for the diagnosis of CRPS. Furthermore, EP300, its paralog CREBBP, and the STAT family genes, STAT3 and STAT5 may be important in the development of CRPS.

Dissection of the cis-2-decenoic acid signaling network in Pseudomonas aeruginosa using microarray technique

PubMed Central

Rahmani-Badi, Azadeh; Sepehr, Shayesteh; Fallahi, Hossein; Heidari-Keshel, Saeed

2015-01-01

Many bacterial pathogens use quorum-sensing (QS) signaling to regulate the expression of factors contributing to virulence and persistence. Bacteria produce signals of different chemical classes. The signal molecule, known as diffusible signal factor (DSF), is a cis-unsaturated fatty acid that was first described in the plant pathogen Xanthomonas campestris. Previous works have shown that human pathogen, Pseudomonas aeruginosa, also synthesizes a structurally related molecule, characterized as cis-2-decenoic acid (C10: Δ2, CDA) that induces biofilm dispersal by multiple types of bacteria. Furthermore, CDA has been shown to be involved in inter-kingdom signaling that modulates fungal behavior. Therefore, an understanding of its signaling mechanism could suggest strategies for interference, with consequences for disease control. To identify the components of CDA signaling pathway in this pathogen, a comparative transcritpome analysis was conducted, in the presence and absence of CDA. A protein-protein interaction (PPI) network for differentially expressed (DE) genes with known function was then constructed by STRING and Cytoscape. In addition, the effects of CDA in combination with antimicrobial agents on the biofilm surface area and bacteria viability were evaluated using fluorescence microscopy and digital image analysis. Microarray analysis identified 666 differentially expressed genes in the presence of CDA and gene ontology (GO) analysis revealed that in P. aeruginosa, CDA mediates dispersion of biofilms through signaling pathways, including enhanced motility, metabolic activity, virulence as well as persistence at different temperatures. PPI data suggested that a cluster of five genes (PA4978, PA4979, PA4980, PA4982, PA4983) is involved in the CDA synthesis and perception. Combined treatments using both CDA and antimicrobial agents showed that following exposure of the biofilms to CDA, remaining cells on the surface were easily removed and killed by antimicrobials. PMID:25972860

Appetitive responses to sexual stimuli are attenuated in individuals with low levels of sexual desire.

PubMed

Giargiari, Tracie D; Mahaffey, Amanda L; Craighead, W Edward; Hutchison, Kent E

2005-10-01

Despite the high prevalence of sexual desire disorders, little is known about their biological underpinnings in humans. Animal studies suggest that dopamine is involved in appetitive sexual behavior; thus, one aim of this study was to elucidate that relationship in humans. This study used measurement of the acoustic startle response (ASR) and prepulse inhibition of the startle response (PPI) as psychophysiological indicators of changes in motivational states to assess the potential relation between sexual desire and appetitive motivation in humans. Responses to sexually provocative stimuli consisting of single nude men and single nude women in a sample of 153 participants (77 men, 76 women) were assessed. The results indicated that ASR was attenuated after exposure to appetitive stimuli (i.e., sexually provocative pictures of attractive individuals) to a greater extent among participants with higher levels of sexual desire, as measured by the Sexual Desire Inventory-2 (Spector, I. P., Carey, M. P., & Steinberg, L. (1996). Journal of Sex & Marital Therapy, 22, 175-190). In addition, PPI was inversely associated with subjective ratings across stimuli such that greater subjective levels of desire were correlated with lower levels of PPI. In general, these results suggest that individuals with lower levels of sexual desire may have a diminished physiological response to appetitive sexual stimuli.

Highly efficient near ultraviolet organic light-emitting diode based on a meta-linked donor–acceptor molecule† †Electronic supplementary information (ESI) available: The details of the synthesis; the ground state and excited state geometries in PPI, TPA–PPI and mTPA–PPI; absorption and emission properties of PPI, TPA–PPI and mTPA–PPI in the gas phase; detailed absorption peak positions, emission peak positions and ηPL values of PPI and mTPA–PPI in different solvents; HOMO and LUMO of mTPA–PPI at ground state; NTO for the S0 → S1 absorption transition in PPI, TPA–PPI and mTPA–PPI; NTO for S0 → Sn electronic transition character in mTPA–PPI; lifetime measurement, radiative transition rates and non-radiative transition rates of PPI and mTPA–PPI in hexane and THF solutions; low-temperature fluorescence and phosphorescence spectra of PPI and mTPA–PPI; CV curves of PPI and mTPA–PPI, and schematic diagram of design principle of mTPA–PPI; TGA and DSC graphs of PPI and mTPA–PPI; current efficiency–current density–power efficiency curves and EL spectra at different driving voltages of PPI and mTPA–PPI devices. See DOI: 10.1039/c5sc01131k

PubMed Central

Liu, Haichao; Bai, Qing; Yao, Liang; Zhang, Haiyan; Xu, Hai; Zhang, Shitong; Li, Weijun; Gao, Yu; Li, Jinyu; Lu, Ping; Wang, Hongyan; Ma, Yuguang

2015-01-01

A novel near ultraviolet (NUV) emitter with a meta-linked donor–acceptor (D–A) structure between triphenylamine (TPA) and phenanthroimidazole (PPI), mTPA–PPI, was designed and synthesized. This molecular design is expected to resolve the conflict between the non-red-shifted emission and the introduction of a charge-transfer (CT) state in the D–A system, aiming at NUV organic light-emitting diodes (OLEDs) with high-efficiency and colour-purity. Theoretical calculations and photophysical experiments were implemented to verify the unique excited state properties of mTPA–PPI. The mTPA–PPI device exhibited excellent NUV electroluminescence (EL) performance with an emission peak at 404 nm, a full width at half maximum (FWHM) of only 47 nm corresponding to a CIE coordinate of (0.161, 0.049), and a maximum external quantum efficiency (EQE) of 3.33%, which is among the best results for NUV OLEDs. This work not only demonstrates the promising potential of mTPA–PPI in NUV OLEDs, but also provides a valuable strategy for the rational design of NUV materials by using the meta-linked D–A architecture. PMID:29218149

How Structure Defines Affinity in Protein-Protein Interactions

PubMed Central

Erijman, Ariel; Rosenthal, Eran; Shifman, Julia M.

2014-01-01

Protein-protein interactions (PPI) in nature are conveyed by a multitude of binding modes involving various surfaces, secondary structure elements and intermolecular interactions. This diversity results in PPI binding affinities that span more than nine orders of magnitude. Several early studies attempted to correlate PPI binding affinities to various structure-derived features with limited success. The growing number of high-resolution structures, the appearance of more precise methods for measuring binding affinities and the development of new computational algorithms enable more thorough investigations in this direction. Here, we use a large dataset of PPI structures with the documented binding affinities to calculate a number of structure-based features that could potentially define binding energetics. We explore how well each calculated biophysical feature alone correlates with binding affinity and determine the features that could be used to distinguish between high-, medium- and low- affinity PPIs. Furthermore, we test how various combinations of features could be applied to predict binding affinity and observe a slow improvement in correlation as more features are incorporated into the equation. In addition, we observe a considerable improvement in predictions if we exclude from our analysis low-resolution and NMR structures, revealing the importance of capturing exact intermolecular interactions in our calculations. Our analysis should facilitate prediction of new interactions on the genome scale, better characterization of signaling networks and design of novel binding partners for various target proteins. PMID:25329579

Highly compressible reduced graphene oxide/polypyrrole/MnO2 aerogel electrodes meeting the requirement of limiting space

NASA Astrophysics Data System (ADS)

Lv, Peng; Tang, Xun; Yuan, Jiajiao; Ji, Chenglong

2017-11-01

Highly compressible electrodes are in high demand in volume-restricted energy storage devices. Superelastic reduced graphene oxide (rGO) aerogel with attractive characteristics are proposed as the promising skeleton for compressible electrodes. Herein, a ternary aerogel was prepared by successively electrodepositing polypyrrole (PPy) and MnO2 into the superelastic rGO aerogel. In the rGO/PPy/MnO2 aerogel, rGO aerogel provides the continuously conductive network; MnO2 is mainly responsible for pseudo reactions; the middle PPy layer not only reduces the interface resistance between rGO and MnO2, but also further enhanced the mechanical strength of rGO backbone. The synergistic effect of the three components leads to excellent performances including high specific capacitance, reversible compressibility, and extreme durability. The gravimetric capacitance of the compressible rGO/PPy/MnO2 aerogel electrodes reaches 366 F g-1 and can retain 95.3% even under 95% compressive strain. And a volumetric capacitance of 138 F cm-3 is achieved, which is much higher than that of other rGO-based compressible electrodes. This volumetric capacitance value can be preserved by 85% after 3500 charge/discharge cycles with various compression conditions. This work will pave the way for advanced applications in the area of compressible energy-storage devices meeting the requirement of limiting space.

Weighted gene co‑expression network analysis in identification of key genes and networks for ischemic‑reperfusion remodeling myocardium.

PubMed

Guo, Nan; Zhang, Nan; Yan, Liqiu; Lian, Zheng; Wang, Jiawang; Lv, Fengfeng; Wang, Yunfei; Cao, Xufen

2018-06-14

Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia‑reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene co‑expression network analysis, hierarchical clustering, protein‑protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene co‑expression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC proto‑oncogene, non‑receptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.

Multi-Dimensional Scaling based grouping of known complexes and intelligent protein complex detection.

PubMed

Rehman, Zia Ur; Idris, Adnan; Khan, Asifullah

2018-06-01

Protein-Protein Interactions (PPI) play a vital role in cellular processes and are formed because of thousands of interactions among proteins. Advancements in proteomics technologies have resulted in huge PPI datasets that need to be systematically analyzed. Protein complexes are the locally dense regions in PPI networks, which extend important role in metabolic pathways and gene regulation. In this work, a novel two-phase protein complex detection and grouping mechanism is proposed. In the first phase, topological and biological features are extracted for each complex, and prediction performance is investigated using Bagging based Ensemble classifier (PCD-BEns). Performance evaluation through cross validation shows improvement in comparison to CDIP, MCode, CFinder and PLSMC methods Second phase employs Multi-Dimensional Scaling (MDS) for the grouping of known complexes by exploring inter complex relations. It is experimentally observed that the combination of topological and biological features in the proposed approach has greatly enhanced prediction performance for protein complex detection, which may help to understand various biological processes, whereas application of MDS based exploration may assist in grouping potentially similar complexes. Copyright © 2018 Elsevier Ltd. All rights reserved.

IP-FCM measures physiologic protein-protein interactions modulated by signal transduction and small-molecule drug inhibition.

PubMed

Smith, Stephen E P; Bida, Anya T; Davis, Tessa R; Sicotte, Hugues; Patterson, Steven E; Gil, Diana; Schrum, Adam G

2012-01-01

Protein-protein interactions (PPI) mediate the formation of intermolecular networks that control biological signaling. For this reason, PPIs are of outstanding interest in pharmacology, as they display high specificity and may represent a vast pool of potentially druggable targets. However, the study of physiologic PPIs can be limited by conventional assays that often have large sample requirements and relatively low sensitivity. Here, we build on a novel method, immunoprecipitation detected by flow cytometry (IP-FCM), to assess PPI modulation during either signal transduction or pharmacologic inhibition by two different classes of small-molecule compounds. First, we showed that IP-FCM can detect statistically significant differences in samples possessing a defined PPI change as low as 10%. This sensitivity allowed IP-FCM to detect a PPI that increases transiently during T cell signaling, the antigen-inducible interaction between ZAP70 and the T cell antigen receptor (TCR)/CD3 complex. In contrast, IP-FCM detected no ZAP70 recruitment when T cells were stimulated with antigen in the presence of the src-family kinase inhibitor, PP2. Further, we tested whether IP-FCM possessed sufficient sensitivity to detect the effect of a second, rare class of compounds called SMIPPI (small-molecule inhibitor of PPI). We found that the first-generation non-optimized SMIPPI, Ro-26-4550, inhibited the IL-2:CD25 interaction detected by IP-FCM. This inhibition was detectable using either a recombinant CD25-Fc chimera or physiologic full-length CD25 captured from T cell lysates. Thus, we demonstrate that IP-FCM is a sensitive tool for measuring physiologic PPIs that are modulated by signal transduction and pharmacologic inhibition.

From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

PubMed

Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

2017-12-01

The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.

PubMed

De Milito, Angelo; Canese, Rossella; Marino, Maria Lucia; Borghi, Martina; Iero, Manuela; Villa, Antonello; Venturi, Giulietta; Lozupone, Francesco; Iessi, Elisabetta; Logozzi, Mariantonia; Della Mina, Pamela; Santinami, Mario; Rodolfo, Monica; Podo, Franca; Rivoltini, Licia; Fais, Stefano

2010-07-01

Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno-transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cells in vitro and induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM-induced tumor cell death occurred via rapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan-caspase inhibitor z-vad-fmk completely abrogated the ESOM-induced cell death. ESOM administration (2.5 mg kg(-1)) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma-bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients.

In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks.

PubMed

Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques; Ferreira, Rafaela Salgado; Silva, Artur; Gromiha, Michael; Ghosh, Preetam; Barh, Debmalya; Azevedo, Vasco; Röttger, Richard

2016-11-04

Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis. Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous. The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.

UDoNC: An Algorithm for Identifying Essential Proteins Based on Protein Domains and Protein-Protein Interaction Networks.

PubMed

Peng, Wei; Wang, Jianxin; Cheng, Yingjiao; Lu, Yu; Wu, Fangxiang; Pan, Yi

2015-01-01

Prediction of essential proteins which are crucial to an organism's survival is important for disease analysis and drug design, as well as the understanding of cellular life. The majority of prediction methods infer the possibility of proteins to be essential by using the network topology. However, these methods are limited to the completeness of available protein-protein interaction (PPI) data and depend on the network accuracy. To overcome these limitations, some computational methods have been proposed. However, seldom of them solve this problem by taking consideration of protein domains. In this work, we first analyze the correlation between the essentiality of proteins and their domain features based on data of 13 species. We find that the proteins containing more protein domain types which rarely occur in other proteins tend to be essential. Accordingly, we propose a new prediction method, named UDoNC, by combining the domain features of proteins with their topological properties in PPI network. In UDoNC, the essentiality of proteins is decided by the number and the frequency of their protein domain types, as well as the essentiality of their adjacent edges measured by edge clustering coefficient. The experimental results on S. cerevisiae data show that UDoNC outperforms other existing methods in terms of area under the curve (AUC). Additionally, UDoNC can also perform well in predicting essential proteins on data of E. coli.

Novelty seeking and reward dependence-related large-scale brain networks functional connectivity variation during salience expectancy.

PubMed

Li, Shijia; Demenescu, Liliana Ramona; Sweeney-Reed, Catherine M; Krause, Anna Linda; Metzger, Coraline D; Walter, Martin

2017-08-01

A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior cingulate cortex (dACC) plays a key role in switching between brain networks during salience detection and attention regulation. Previous fMRI studies have associated expectancy behaviors and SN activation with novelty seeking (NS) and reward dependence (RD) personality traits. To address the question of how functional connectivity (FC) in the SN is modulated by internal (expectancy-related) salience assignment and different personality traits, 68 healthy participants performed a salience expectancy task using functional magnetic resonance imaging, and psychophysiological interaction analysis (PPI) was conducted to determine salience-related connectivity changes during these anticipation periods. Correlation was then evaluated between PPI and personality traits, assessed using the temperament and character inventory of 32 male participants. During high salience expectancy, SN-seed regions showed reduced FC to visual areas and parts of the default mode network, but increased FC to the central executive network. With increasing NS, participants showed significantly increasing disconnection between right AI and middle cingulate cortex when expecting high-salience pictures as compared to low-salience pictures, while increased RD also predicted decreased right dACC and caudate FC for high salience expectancy. Our findings suggest a direct link between personality traits and internal salience processing mediated by differential network integration of the SN. SN activity and coordination may therefore be moderated by novelty seeking and reward dependency personality traits, which are associated with risk of addiction. Hum Brain Mapp 38:4064-4077, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Visible light photoelectrochemical aptasensor for adenosine detection based on CdS/PPy/g-C3N4 nanocomposites.

PubMed

Liu, Yixin; Ma, Hongmin; Zhang, Yong; Pang, Xuehui; Fan, Dawei; Wu, Dan; Wei, Qin

2016-12-15

In this work, a label-free photoelectrochemical (PEC) aptasensor was developed for adenosine detection based on CdS/PPy/g-C3N4 nanocomposites. The CdS/g-C3N4 heterojunction effectively prevented the photogenerated charges recombination of g-C3N4 and self-photocorrosion processes of CdS, improving photo-to-current conversion efficiency. The introduced polypyrrole (PPy) nanoparticles could lead to a more effective separation of photogenerated charges, thus resulting in a further increasing of photocurrent. The CdS/PPy/g-C3N4 was firstly employed as the photoactive materials for fabrication of aptasensor, and SH-aptamer was then adsorbed on the CdS/PPy/g-C3N4 modified electrodes through S-Cd bond. With increasing of adenosine concentration, the photocurrent decreased as the formation of SH-aptamer-adenosine bioaffinity complexes. Under optimal conditions, the PEC aptasensor had a sensitive response to adenosine in a linear range of 0.3nmolL(-1) to 200nmolL(-1) with a detection limit of 0.1nmolL(-1). Besides, the as-proposed aptasensor has also been applied in human serum samples analysis. The aptasensor exhibits high sensitivity and good stability, thus opening up a new promising PEC platform for some other small molecules analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

The extent, quality and impact of patient and public involvement in primary care research: a mixed methods study.

PubMed

Blackburn, Steven; McLachlan, Sarah; Jowett, Sue; Kinghorn, Philip; Gill, Paramjit; Higginbottom, Adele; Rhodes, Carol; Stevenson, Fiona; Jinks, Clare

2018-01-01

In the UK, more patients go to primary care than other parts of the health service. Therefore it is important for research into primary care to include the insights and views of people who receive these services. To explore the extent, quality and impact of patient and public involvement (PPI) in primary care research, we examined documents of 200 projects and surveyed 191 researchers.We found that about half of studies included PPI to develop research ideas and during the study itself. Common activities included designing study materials, advising on methods, and managing the research. Some studies did not undertake the PPI activities initially planned and funded for. PPI varied by study design, health condition and study population. We found pockets of good practice: having a PPI budget, supporting PPI contributors, and PPI informing recruitment issues. However, good practice was lacking in other areas. Few projects offered PPI contributors training, used PPI to develop information for participants about study progress and included PPI to advise on publishing findings.Researchers reported beneficial impacts of PPI. Most impact was reported when the approach to PPI included more indicators of good practice. The main cost of PPI for researchers was their time. Many reported difficulties providing information about PPI.In partnership with PPI contributors, we have used these findings to develop:a new Cost and Consequences Framework for PPI highlighting financial and non-financial costs, benefits and harms of PPIFifteen co-produced recommendations to improve the practice and delivery of PPI. Background: To improve the lives of patients in primary care requires the involvement of service users in primary care research. We aimed to explore the extent, quality and impact of patient and public involvement (PPI) in primary care research. Methods: We extracted information about PPI from grant applications, reports and an electronic survey of researchers of studies funded by the NIHR School for Primary Care Research (SPCR). We applied recognised quality indicators to assess the quality of PPI and assessed its impact on research. Results: We examined 200 grant applications and reports of 181 projects. PPI was evident in the development of 47 (24%) grant applications. 113 (57%) grant applications included plans for PPI during the study, mostly in study design, oversight, and dissemination. PPI during projects was reported for 83 (46%) projects, including designing study materials and managing the research. We identified inconsistencies between planned and reported PPI. PPI varied by study design, health condition and study population.Of 46 (24%) of 191 questionnaires completed, 15 reported PPI activity. Several projects showed best practice according to guidelines, in terms of having a PPI budget, supporting PPI contributors, and PPI informing recruitment issues. However few projects offered PPI contributors training, used PPI to develop information for participants about study progress, and had PPI in advising on dissemination.Beneficial impacts of PPI in designing studies and writing participant information was frequently reported. Less impact was reported on developing funding applications, managing or carrying out the research. The main cost of PPI for researchers was their time. Many researchers found it difficult to provide information about PPI activities.Our findings informed:a new Cost and Consequences Framework for PPI in primary care research highlighting financial and non-financial costs, plus the benefits and harms of PPIFifteen co-produced recommendations to improve PPI in research and within the SPCR. Conclusions: The extent, quality and impact of PPI in primary care research is inconsistent across research design and topics. Pockets of good practice were identified making a positive impact on research. The new Cost and Consequences Framework may help others assess the impact of PPI.

From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials

PubMed Central

Buck, Deborah; Gamble, Carrol; Dudley, Louise; Preston, Jennifer; Hanley, Bec; Williamson, Paula R; Young, Bridget

2014-01-01

Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. Objective Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. Methods We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers’ and PPI contributors’ interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. Results Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors’ lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding ‘the right’ PPI contributors, and advised caution when involving investigators’ current patients. Conclusions Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPI's success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trial's distinct needs. Monitoring and reporting PPI before, during and after trials will help the research community to optimise PPI, although the need for ongoing flexibility in implementing PPI should also be recognised. PMID:25475243

Brain networks involved in tactile speed classification of moving dot patterns: the effects of speed and dot periodicity

PubMed Central

Yang, Jiajia; Kitada, Ryo; Kochiyama, Takanori; Yu, Yinghua; Makita, Kai; Araki, Yuta; Wu, Jinglong; Sadato, Norihiro

2017-01-01

Humans are able to judge the speed of an object’s motion by touch. Research has suggested that tactile judgment of speed is influenced by physical properties of the moving object, though the neural mechanisms underlying this process remain poorly understood. In the present study, functional magnetic resonance imaging was used to investigate brain networks that may be involved in tactile speed classification and how such networks may be affected by an object’s texture. Participants were asked to classify the speed of 2-D raised dot patterns passing under their right middle finger. Activity in the parietal operculum, insula, and inferior and superior frontal gyri was positively related to the motion speed of dot patterns. Activity in the postcentral gyrus and superior parietal lobule was sensitive to dot periodicity. Psycho-physiological interaction (PPI) analysis revealed that dot periodicity modulated functional connectivity between the parietal operculum (related to speed) and postcentral gyrus (related to dot periodicity). These results suggest that texture-sensitive activity in the primary somatosensory cortex and superior parietal lobule influences brain networks associated with tactually-extracted motion speed. Such effects may be related to the influence of surface texture on tactile speed judgment. PMID:28145505

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

A Multi-Method Approach for Proteomic Network Inference in 11 Human Cancers.

PubMed

Şenbabaoğlu, Yasin; Sümer, Selçuk Onur; Sánchez-Vega, Francisco; Bemis, Debra; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

2016-02-01

Protein expression and post-translational modification levels are tightly regulated in neoplastic cells to maintain cellular processes known as 'cancer hallmarks'. The first Pan-Cancer initiative of The Cancer Genome Atlas (TCGA) Research Network has aggregated protein expression profiles for 3,467 patient samples from 11 tumor types using the antibody based reverse phase protein array (RPPA) technology. The resultant proteomic data can be utilized to computationally infer protein-protein interaction (PPI) networks and to study the commonalities and differences across tumor types. In this study, we compare the performance of 13 established network inference methods in their capacity to retrieve the curated Pathway Commons interactions from RPPA data. We observe that no single method has the best performance in all tumor types, but a group of six methods, including diverse techniques such as correlation, mutual information, and regression, consistently rank highly among the tested methods. We utilize the high performing methods to obtain a consensus network; and identify four robust and densely connected modules that reveal biological processes as well as suggest antibody-related technical biases. Mapping the consensus network interactions to Reactome gene lists confirms the pan-cancer importance of signal transduction pathways, innate and adaptive immune signaling, cell cycle, metabolism, and DNA repair; and also suggests several biological processes that may be specific to a subset of tumor types. Our results illustrate the utility of the RPPA platform as a tool to study proteomic networks in cancer.

Construction and analysis of protein-protein interaction network correlated with ankylosing spondylitis.

PubMed

Kanwal, Attiya; Fazal, Sahar

2018-01-05

Ankylosing spondylitis, a systemic illness is a foundation of progressing joint swelling that for the most part influences the spine. However, it frequently causes aggravation in different joints far from the spine, and in addition organs, for example, the eyes, heart, lungs, and kidneys. It's an immune system ailment that may be activated by specific sorts of bacterial or viral diseases that initiate an invulnerable reaction that don't close off after the contamination is recuperated. The particular reason for ankylosing spondylitis is obscure, yet hereditary qualities assume a huge part in this condition. The rising apparatuses of network medicine offer a stage to investigate an unpredictable illness at framework level. In this study, we meant to recognize the key proteins and the biological regulator pathways including in AS and further investigating the molecular connectivity between these pathways by the topological examination of the Protein-protein communication (PPI) system. The extended network including of 93 nodes and have 199 interactions respectively scanned from STRING database and some separated small networks. 24 proteins with high BC at the threshold of 0.01 and 55 proteins with large degree at the threshold of 1 have been identified. CD4 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for AS and the crosstalk between them. The finding of this research suggests that AS variation is orchestrated by an integrated PPI network centered on CD4 out of 93 nodes. Ankylosing spondylitis, a systemic disease is an establishment of advancing joint swelling that generally impacts the spine. Be that as it may, it as often as possible causes disturbance in various joints a long way from the spine, and what's more organs. It's a resistant framework affliction that might be actuated by particular sorts of bacterial or viral ailments that start an immune response that don't shut off after the pollution is recovered. The specific explanation behind AS is dark, yet innate qualities expect a colossal part in this condition. The rising devices of system solution offer a phase to examine an erratic ailment at structure level. In this study, we intended to perceive the key proteins and the natural controller pathways incorporating into AS. The finding of this research proposes that AS variety is organized by a coordinated PPI system focused on CD4. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines.

PubMed

Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

2016-08-15

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96h and human cancer cell lines for 24h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7μM at 24 and 48hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values≥402μM (PAMAMs) and ≤240μM (PPIs) for HepG2 and ≤13.24μM (PAMAMs) and ≤12.84μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of the Key Genes and Pathways in Esophageal Carcinoma.

PubMed

Su, Peng; Wen, Shiwang; Zhang, Yuefeng; Li, Yong; Xu, Yanzhao; Zhu, Yonggang; Lv, Huilai; Zhang, Fan; Wang, Mingbo; Tian, Ziqiang

2016-01-01

Objective . Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods . 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results . A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion . The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

Dynamic Changes in Amygdala Psychophysiological Connectivity Reveal Distinct Neural Networks for Facial Expressions of Basic Emotions.

PubMed

Diano, Matteo; Tamietto, Marco; Celeghin, Alessia; Weiskrantz, Lawrence; Tatu, Mona-Karina; Bagnis, Arianna; Duca, Sergio; Geminiani, Giuliano; Cauda, Franco; Costa, Tommaso

2017-03-27

The quest to characterize the neural signature distinctive of different basic emotions has recently come under renewed scrutiny. Here we investigated whether facial expressions of different basic emotions modulate the functional connectivity of the amygdala with the rest of the brain. To this end, we presented seventeen healthy participants (8 females) with facial expressions of anger, disgust, fear, happiness, sadness and emotional neutrality and analyzed amygdala's psychophysiological interaction (PPI). In fact, PPI can reveal how inter-regional amygdala communications change dynamically depending on perception of various emotional expressions to recruit different brain networks, compared to the functional interactions it entertains during perception of neutral expressions. We found that for each emotion the amygdala recruited a distinctive and spatially distributed set of structures to interact with. These changes in amygdala connectional patters characterize the dynamic signature prototypical of individual emotion processing, and seemingly represent a neural mechanism that serves to implement the distinctive influence that each emotion exerts on perceptual, cognitive, and motor responses. Besides these differences, all emotions enhanced amygdala functional integration with premotor cortices compared to neutral faces. The present findings thus concur to reconceptualise the structure-function relation between brain-emotion from the traditional one-to-one mapping toward a network-based and dynamic perspective.

Development and application of a recombination-based library versus library high- throughput yeast two-hybrid (RLL-Y2H) screening system.

PubMed

Yang, Fang; Lei, Yingying; Zhou, Meiling; Yao, Qili; Han, Yichao; Wu, Xiang; Zhong, Wanshun; Zhu, Chenghang; Xu, Weize; Tao, Ran; Chen, Xi; Lin, Da; Rahman, Khaista; Tyagi, Rohit; Habib, Zeshan; Xiao, Shaobo; Wang, Dang; Yu, Yang; Chen, Huanchun; Fu, Zhenfang; Cao, Gang

2018-02-16

Protein-protein interaction (PPI) network maintains proper function of all organisms. Simple high-throughput technologies are desperately needed to delineate the landscape of PPI networks. While recent state-of-the-art yeast two-hybrid (Y2H) systems improved screening efficiency, either individual colony isolation, library preparation arrays, gene barcoding or massive sequencing are still required. Here, we developed a recombination-based 'library vs library' Y2H system (RLL-Y2H), by which multi-library screening can be accomplished in a single pool without any individual treatment. This system is based on the phiC31 integrase-mediated integration between bait and prey plasmids. The integrated fragments were digested by MmeI and subjected to deep sequencing to decode the interaction matrix. We applied this system to decipher the trans-kingdom interactome between Mycobacterium tuberculosis and host cells and further identified Rv2427c interfering with the phagosome-lysosome fusion. This concept can also be applied to other systems to screen protein-RNA and protein-DNA interactions and delineate signaling landscape in cells.

Expression and characterization of recombinant pyruvate phosphate dikinase from Entamoeba histolytica.

PubMed

Saavedra-Lira, E; Ramirez-Silva, L; Perez-Montfort, R

1998-01-15

The parasite Entamoeba histolytica is an organism whose main energetic source comes from glycolysis. It has the singularity that several of its glycolytic enzymes use pyrophosphate as an alternative phosphate donor. Thus, pyruvate phosphate dikinase (PPDK), an inorganic pyrophosphate (PPi)-dependent enzyme, substitutes pyruvate kinase present in humans. We previously cloned and sequenced the gene that codifies for PPDK in E. histolytica. We now report its expression in a bacterial system and its purification to 98% homogeneity. We determined its K(m) for phosphoenolpyruvate, AMP and PPi (21, < 5 and 100 microM, respectively). Unlike PPDK from maize and bacteria and pyruvate kinase from other cells, EhPPDk is dependent on divalent cations but does not require monovalent cations for activity. The enzyme has an optimum pH of 6.0, it is labile to low temperatures and has a tetrameric structure. Since EhPPDK is a PPi-dependent enzyme, we also tested the effect of some pyrophosphate analogs as inhibitors of activity. Studies on the function and structure of this enzyme may be important for therapeutic research in several parasitic diseases, since it has no counterpart in humans.

Comparison of planar, PET and well-counter measurements of total tumor radioactivity in a mouse xenograft model.

PubMed

Green, Michael V; Seidel, Jurgen; Williams, Mark R; Wong, Karen J; Ton, Anita; Basuli, Falguni; Choyke, Peter L; Jagoda, Elaine M

2017-10-01

Quantitative small animal radionuclide imaging studies are often carried out with the intention of estimating the total radioactivity content of various tissues such as the radioactivity content of mouse xenograft tumors exposed to putative diagnostic or therapeutic agents. We show that for at least one specific application, positron projection imaging (PPI) and PET yield comparable estimates of absolute total tumor activity and that both of these estimates are highly correlated with direct well-counting of these same tumors. These findings further suggest that in this particular application, PPI is a far more efficient data acquisition and processing methodology than PET. Forty-one athymic mice were implanted with PC3 human prostate cancer cells transfected with prostate-specific membrane antigen (PSMA (+)) and one additional animal (for a total of 42) with a control blank vector (PSMA (-)). All animals were injected with [ 18 F] DCFPyl, a ligand for PSMA, and imaged for total tumor radioactivity with PET and PPI. The tumors were then removed, assayed by well counting for total radioactivity and the values between these methods intercompared. PET, PPI and well-counter estimates of total tumor radioactivity were highly correlated (R 2 >0.98) with regression line slopes near unity (0.95

Generic Information Can Retrieve Known Biological Associations: Implications for Biomedical Knowledge Discovery

PubMed Central

van Haagen, Herman H. H. B. M.; 't Hoen, Peter A. C.; Mons, Barend; Schultes, Erik A.

2013-01-01

Motivation Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins) others generic (e.g., ‘Homo sapiens’). Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI) by filtering generic concepts (node filtering) or links to generic concepts (edge filtering) from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering), and assessed the retrieval performance of networks composed of generic information alone. Results Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept “binding” is indicative for PPI retrieval and the concept “mutation abnormality” is indicative for gene-disease associations. Conclusion Generic concepts are important for information retrieval and cannot be removed from semantic networks without negative impact on retrieval performance. PMID:24260124

Integration of RNA-Seq and RPPA data for survival time prediction in cancer patients.

PubMed

Isik, Zerrin; Ercan, Muserref Ece

2017-10-01

Integration of several types of patient data in a computational framework can accelerate the identification of more reliable biomarkers, especially for prognostic purposes. This study aims to identify biomarkers that can successfully predict the potential survival time of a cancer patient by integrating the transcriptomic (RNA-Seq), proteomic (RPPA), and protein-protein interaction (PPI) data. The proposed method -RPBioNet- employs a random walk-based algorithm that works on a PPI network to identify a limited number of protein biomarkers. Later, the method uses gene expression measurements of the selected biomarkers to train a classifier for the survival time prediction of patients. RPBioNet was applied to classify kidney renal clear cell carcinoma (KIRC), glioblastoma multiforme (GBM), and lung squamous cell carcinoma (LUSC) patients based on their survival time classes (long- or short-term). The RPBioNet method correctly identified the survival time classes of patients with between 66% and 78% average accuracy for three data sets. RPBioNet operates with only 20 to 50 biomarkers and can achieve on average 6% higher accuracy compared to the closest alternative method, which uses only RNA-Seq data in the biomarker selection. Further analysis of the most predictive biomarkers highlighted genes that are common for both cancer types, as they may be driver proteins responsible for cancer progression. The novelty of this study is the integration of a PPI network with mRNA and protein expression data to identify more accurate prognostic biomarkers that can be used for clinical purposes in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic factors and genes associated with endometrial cancer based on gene expression profiling by bioinformatics analysis.

PubMed

Zhang, Ying; Zhang, Wei; Li, Xinglan; Li, Dapeng; Zhang, Xiaoling; Yin, Yajie; Deng, Xiangyun; Sheng, Xiugui

2016-06-01

Endometrial cancer (EC) is the most prevalent malignancy worldwide. Although several efforts had been made to explore the molecular mechanism responsible for EC progression, it is still not fully understood. To evaluate the clinical characteristics and prognostic factors of patients with EC, and further to search for novel genes associated with EC progression. We recruited 328 patients with EC and analyzed prognostic factors using Cox proportional hazard regression model. Further, a gene expression profile of EC was used to identify the differentially expressed genes (DEGs) between normal samples and tumor samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis ( http://www.genome.jp/kegg/ ) for DEGs were performed, and then protein-protein interaction (PPI) network of DEGs as well as the subnetwork of PPI were constructed with plug-in, MCODE by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes database. Our results showed that body mass index (BMI), hypertension, myometrial invasion, pathological type, and Glut4 positive expression were prognostic factors in EC (P < 0.05). Bioinformatics analysis showed that upregulated DEGs were associated with cell cycle, and downregulated DEGs were related to MAPK pathway. Meanwhile, PPI network analysis revealed that upregulated CDK1 and CCNA2 as well as downregulated JUN and FOS were listed in top two nodes with high degrees. Patients with EC should be given more focused attentions in respect of pathological type, BMI, hypertension, and Glut4-positive expression. In addition, CDK1, CCNA2, JUN, and FOS might play important roles in EC development.

A constriction resistance model of conjugated polymer based piezoresistive sensors for electronic skin applications.

PubMed

Khalili, N; Naguib, H E; Kwon, R H

2016-05-14

Human intervention can be replaced through the development of tools resulting from utilization of sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. It is shown that the electrical conductivity of the fabricated PPy based piezoresistive sensors is enhanced as a result of adding conductive fillers and therefore, endowing the sensors with a higher sensitivity. A semi-analytical constriction resistance based model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and its corresponding sensitivity is obtained. Comparing the results with their experimental counterparts, the proposed modeling methodology offers a good tracking ability.

Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats.

PubMed

Wu, Zhe-Meng; Ding, Yu; Jia, Hong-Xiao; Li, Liang

2016-09-01

Prepulse inhibition (PPI) is suppression of the startle reflex by a weaker sensory stimulus (prepulse) preceding the startling stimulus. In people with schizophrenia, impairment of attentional modulation of PPI, but not impairment of baseline PPI, is correlated with symptom severity. In rats, both fear conditioning of prepulse and perceptually spatial separation between the conditioned prepulse and a noise masker enhance PPI (the paradigms of attentional modulation of PPI). As a neurodevelopmental model of schizophrenia, isolation rearing impairs both baseline PPI and attentional modulations of PPI in rats. This study examined in Sprague-Dawley male rats whether neonatally blocking N-methyl-D-aspartate (NMDA) receptors specifically affects attentional modulations of PPI during adulthood. Both socially reared rats with neonatal exposure to the NMDA receptor antagonist MK-801 and isolation-reared rats exhibited augmented startle responses, but only isolation rearing impaired baseline PPI. Fear conditioning of the prepulse enhanced PPI in socially reared rats, but MK-801-treated rats lost the prepulse feature specificity. Perceptually spatial separation between the conditioned prepulse and a noise masker further enhanced PPI only in normally reared rats. Clozapine administration during adulthood generally weakened startle, enhanced baseline PPI in neonatally interrupted rats, and restored the fear conditioning-induced PPI enhancement in isolation-reared rats with a loss of the prepulse feature specificity. Clozapine administration also abolished both the perceptual separation-induced PPI enhancement in normally reared rats and the fear conditioning-induced PPI enhancement in MK-801-treated rats. Isolation rearing impairs both baseline PPI and attentional modulations of PPI, but neonatally disrupting NMDA receptor-mediated transmissions specifically impair attentional modulations of PPI. Clozapine has limited alleviating effects.

Prediction of protein-protein interaction network using a multi-objective optimization approach.

PubMed

Chowdhury, Archana; Rakshit, Pratyusha; Konar, Amit

2016-06-01

Protein-Protein Interactions (PPIs) are very important as they coordinate almost all cellular processes. This paper attempts to formulate PPI prediction problem in a multi-objective optimization framework. The scoring functions for the trial solution deal with simultaneous maximization of functional similarity, strength of the domain interaction profiles, and the number of common neighbors of the proteins predicted to be interacting. The above optimization problem is solved using the proposed Firefly Algorithm with Nondominated Sorting. Experiments undertaken reveal that the proposed PPI prediction technique outperforms existing methods, including gene ontology-based Relative Specific Similarity, multi-domain-based Domain Cohesion Coupling method, domain-based Random Decision Forest method, Bagging with REP Tree, and evolutionary/swarm algorithm-based approaches, with respect to sensitivity, specificity, and F1 score.

RNA sequencing reveals significant miRNAs in Atypical endometrial hyperplasia.

PubMed

Tang, Shiqian; Dai, Yinmei

2018-06-01

In this paper, we aimed to investigate the miRNAs that played a regulatory role in the development of atypical endometrial hyperplasia (AEH). RNA sequencing was performed for endometrial tissues from 3 AEH patients and 3 endometrial normal hyperplasia patients. RNA sequencing data were processed and differentially expressed (DE) miRNAs were identified between AEH and controls. The target genes for DE miRNAs were identified and mapped to the protein-protein interaction (PPI) network. The miRNA related functions were predicted and miRNA-disease gene network was constructed. Total 18 DE miRNAs were overlapped in three sample groups, among which hsa-miR-577, hsa-miR-182-5p and hsa-miR-183-5p were top three miRNAs that targeting largest number of genes. Function analysis showed that the 18 overlapped miRNAs mainly related with cancer and signaling transduction related pathways. PPI network showed that total 12 genes were among top 20 genes based on three network topological features including BCL2, UMPS, MAPK13, PRKCB, CREB1, IGF1, SP1, SMAD3, IGF1R, NOTCH2, WNT5A, TK2. Top 10 miRNAs in miRNA-disease gene network were identified such as hsa-miR-577 (degree = 17), hsa-miR-182-5p (degree = 16) and hsa-miR-3609 (degree = 13). hsa-miR-577 and hsa-miR-182-5p may play regulatory role in AEH through AMPK signal pathway and Wnt signaling pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

SYSTEMS BIOLOGY ANALYSES OF GENE EXPRESSION AND GENOME WIDE ASSOCIATION STUDY DATA IN OBSTRUCTIVE SLEEP APNEA

PubMed Central

LIU, YU; PATEL, SANJAY; NIBBE, ROD; MAXWELL, SEAN; CHOWDHURY, SALIM A.; KOYUTURK, MEHMET; ZHU, XIAOFENG; LARKIN, EMMA K.; BUXBAUM, SARAH G; PUNJABI, NARESH M.; GHARIB, SINA A.; REDLINE, SUSAN; CHANCE, MARK R.

2015-01-01

The precise molecular etiology of obstructive sleep apnea (OSA) is unknown; however recent research indicates that several interconnected aberrant pathways and molecular abnormalities are contributors to OSA. Identifying the genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment. Towards these goals, we have integrated relevant high dimensional data from various sources, such as genome-wide expression data (microarray), protein-protein interaction (PPI) data and results from genome-wide association studies (GWAS) in order to define sub-network elements that connect some of the known pathways related to the disease as well as define novel regulatory modules related to OSA. Two distinct approaches are applied to identify sub-networks significantly associated with OSA. In the first case we used a biased approach based on sixty genes/proteins with known associations with sleep disorders and/or metabolic disease to seed a search using commercial software to discover networks associated with disease followed by information theoretic (mutual information) scoring of the sub-networks. In the second case we used an unbiased approach and generated an interactome constructed from publicly available gene expression profiles and PPI databases, followed by scoring of the network with p-values from GWAS data derived from OSA patients to uncover sub-networks significant for the disease phenotype. A comparison of the approaches reveals a number of proteins that have been previously known to be associated with OSA or sleep. In addition, our results indicate a novel association of Phosphoinositide 3-kinase, the STAT family of proteins and its related pathways with OSA. PMID:21121029

Minimum curvilinearity to enhance topological prediction of protein interactions by network embedding

PubMed Central

Cannistraci, Carlo Vittorio; Alanis-Lobato, Gregorio; Ravasi, Timothy

2013-01-01

Motivation: Most functions within the cell emerge thanks to protein–protein interactions (PPIs), yet experimental determination of PPIs is both expensive and time-consuming. PPI networks present significant levels of noise and incompleteness. Predicting interactions using only PPI-network topology (topological prediction) is difficult but essential when prior biological knowledge is absent or unreliable. Methods: Network embedding emphasizes the relations between network proteins embedded in a low-dimensional space, in which protein pairs that are closer to each other represent good candidate interactions. To achieve network denoising, which boosts prediction performance, we first applied minimum curvilinear embedding (MCE), and then adopted shortest path (SP) in the reduced space to assign likelihood scores to candidate interactions. Furthermore, we introduce (i) a new valid variation of MCE, named non-centred MCE (ncMCE); (ii) two automatic strategies for selecting the appropriate embedding dimension; and (iii) two new randomized procedures for evaluating predictions. Results: We compared our method against several unsupervised and supervisedly tuned embedding approaches and node neighbourhood techniques. Despite its computational simplicity, ncMCE-SP was the overall leader, outperforming the current methods in topological link prediction. Conclusion: Minimum curvilinearity is a valuable non-linear framework that we successfully applied to the embedding of protein networks for the unsupervised prediction of novel PPIs. The rationale for our approach is that biological and evolutionary information is imprinted in the non-linear patterns hidden behind the protein network topology, and can be exploited for predicting new protein links. The predicted PPIs represent good candidates for testing in high-throughput experiments or for exploitation in systems biology tools such as those used for network-based inference and prediction of disease-related functional modules. Availability: https://sites.google.com/site/carlovittoriocannistraci/home Contact: kalokagathos.agon@gmail.com or timothy.ravasi@kaust.edu.sa Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23812985

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bodewein, Lambert

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, withmore » EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. • Anionic PAMAM dendrimers showed little to no toxicity in fish embryos and cells.« less

Predicting protein complexes using a supervised learning method combined with local structural information.

PubMed

Dong, Yadong; Sun, Yongqi; Qin, Chao

2018-01-01

The existing protein complex detection methods can be broadly divided into two categories: unsupervised and supervised learning methods. Most of the unsupervised learning methods assume that protein complexes are in dense regions of protein-protein interaction (PPI) networks even though many true complexes are not dense subgraphs. Supervised learning methods utilize the informative properties of known complexes; they often extract features from existing complexes and then use the features to train a classification model. The trained model is used to guide the search process for new complexes. However, insufficient extracted features, noise in the PPI data and the incompleteness of complex data make the classification model imprecise. Consequently, the classification model is not sufficient for guiding the detection of complexes. Therefore, we propose a new robust score function that combines the classification model with local structural information. Based on the score function, we provide a search method that works both forwards and backwards. The results from experiments on six benchmark PPI datasets and three protein complex datasets show that our approach can achieve better performance compared with the state-of-the-art supervised, semi-supervised and unsupervised methods for protein complex detection, occasionally significantly outperforming such methods.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

PubMed

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

A fast and high performance multiple data integration algorithm for identifying human disease genes

PubMed Central

2015-01-01

Background Integrating multiple data sources is indispensable in improving disease gene identification. It is not only due to the fact that disease genes associated with similar genetic diseases tend to lie close with each other in various biological networks, but also due to the fact that gene-disease associations are complex. Although various algorithms have been proposed to identify disease genes, their prediction performances and the computational time still should be further improved. Results In this study, we propose a fast and high performance multiple data integration algorithm for identifying human disease genes. A posterior probability of each candidate gene associated with individual diseases is calculated by using a Bayesian analysis method and a binary logistic regression model. Two prior probability estimation strategies and two feature vector construction methods are developed to test the performance of the proposed algorithm. Conclusions The proposed algorithm is not only generated predictions with high AUC scores, but also runs very fast. When only a single PPI network is employed, the AUC score is 0.769 by using F2 as feature vectors. The average running time for each leave-one-out experiment is only around 1.5 seconds. When three biological networks are integrated, the AUC score using F3 as feature vectors increases to 0.830, and the average running time for each leave-one-out experiment takes only about 12.54 seconds. It is better than many existing algorithms. PMID:26399620

A Generalized Form of Context-Dependent Psychophysiological Interactions (gPPI): A Comparison to Standard Approaches

PubMed Central

McLaren, Donald G.; Ries, Michele L.; Xu, Guofan; Johnson, Sterling C.

2012-01-01

Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner. The current implementation of PPI in Statistical Parametric Mapping (SPM8) is configured primarily to assess connectivity differences between two task conditions, when in practice fMRI tasks frequently employ more than two conditions. Here we evaluate how a generalized form of context-dependent PPI (gPPI; http://www.nitrc.org/projects/gppi), which is configured to automatically accommodate more than two task conditions in the same PPI model by spanning the entire experimental space, compares to the standard implementation in SPM8. These comparisons are made using both simulations and an empirical dataset. In the simulated dataset, we compare the interaction beta estimates to their expected values and model fit using the Akaike Information Criterion (AIC). We found that interaction beta estimates in gPPI were robust to different simulated data models, were not different from the expected beta value, and had better model fits than when using standard PPI (sPPI) methods. In the empirical dataset, we compare the model fit of the gPPI approach to sPPI. We found that the gPPI approach improved model fit compared to sPPI. There were several regions that became non-significant with gPPI. These regions all showed significantly better model fits with gPPI. Also, there were several regions where task-dependent connectivity was only detected using gPPI methods, also with improved model fit. Regions that were detected with all methods had more similar model fits. These results suggest that gPPI may have greater sensitivity and specificity than standard implementation in SPM. This notion is tempered slightly as there is no gold standard; however, data simulations with a known outcome support our conclusions about gPPI. In sum, the generalized form of context-dependent PPI approach has increased flexibility of statistical modeling, and potentially improves model fit, specificity to true negative findings, and sensitivity to true positive findings. PMID:22484411

Optical band gap determination of calcium doped lanthanum manganite nano particle tailored with polypyrrole

NASA Astrophysics Data System (ADS)

Gopalakrishna, Smitha Mysore; Murugendrappa, Malalkere Veerappa

2018-05-01

In this paper we bring forth the effect of La0.7Ca0.3MnO3 (LCM) perovskite nano particle on the optical band gap in composition with conducting Polypyrrole (PPy) prepared by chemical oxidation method. The morphology and crystalline phase were determined by SEM, TEM and X-Ray diffraction studies. The Optical band gap studies were analyzed using the UV-VIS spectrometer scanned in the range 200 nm to 600 nm for pure PPy and PPy/LCM composites. There is a characteristic peak observed for the composites situated around 315 nm for pure PPy, PPy/LCM10 and PPy/LCM50. But for higher compositions of LCM weight percentage like 30%, 40% and 50% the peak shift slightly to higher wavelength side. The peak shifts to 320 nm, 325 nm and 335 nm respectively. The optical band gap increased for Pure PPy, PPy/LCM10 and PPy/LCM20 and found to decrease gradually for PPy/LCM30, PPy/LCM40 and PPy/LCM50. The studies suggest that LCM composition in the PPy chain has a role in modifying the wavelength and in turn its band gap. The study may find application in organic devices working at high frequency and voltage.

Identification of Hub Genes and Pathways in Zika Virus Infection Using RNA-Seq Data: A Network-Based Computational Approach.

PubMed

Brahma, Rahul; Gurumayum, Sanathoi; Naorem, Leimarembi Devi; Muthaiyan, Mathavan; Gopal, Jeyakodi; Venkatesan, Amouda

2018-05-01

Zika virus (ZIKV), a single-strand RNA flavivirus, is transmitted primarily through Aedes aegypti. The recent outbreaks in America and unexpected association between ZIKV infection and birth defects have triggered the global attention. This vouches to understand the molecular mechanisms of ZIKV infection to develop effective drug therapy. A systems-level understanding of biological process affected by ZIKV infection in fetal brain sample led us to identify the candidate genes for pharmaceutical intervention and potential biomarkers for diagnosis. To identify the key genes, transcriptomics data (RNA-Seq) with GSE93385 of ZIKV (Strain: MR766) infected human fetal neural stem cell are analyzed. In total, 1,084 differentially expressed genes (DEGs) are identified, that is, 471 upregulated and 613 downregulated genes. Further analysis such as the gene ontology term suggested that the downregulated genes are mostly enriched in defense response to virus, receptor binding, laminin binding, extracellular matrix, endoplasmic reticulum, and for upregulated DEGs: translation initiation, RNA binding, cytosol, and nucleosome are enriched. And through pathway analysis, systemic lupus erythematosus (SLE) is found to be the most enriched pathway. Protein-protein interaction (PPI) network is constructed to find the hub genes using STRING database. The seven key genes namely cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), histone cluster 1 H2B family member K, (HIST1H2BK) histone cluster 1 H2B family member O (HIST1H2BO), and histone cluster 1 H2B family member B (HIST1H2BB), polo-like kinase 1 (PLK1), and cell division cycle 20 (CDC20) with highest degree are found to be hub genes using Centiscape, a Cytoscape plugin. The modules of PPI network using Molecular Complex Detection plugin are found significant in structural constituent of ribosome, defense response to virus, nucleosome, SLE, extracellular region, and regulation of gene silencing. Thus, identified key hub genes and pathways shed light on molecular mechanism that may contribute to the discovery of novel therapeutic targets and development of new strategies for the intervention of ZIKV disease.

Influence of pea protein aggregates on the structure and stability of pea protein/soybean polysaccharide complex emulsions.

PubMed

Yin, Baoru; Zhang, Rujing; Yao, Ping

2015-03-20

The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS), and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry.

PPCM: Combing multiple classifiers to improve protein-protein interaction prediction

DOE PAGES

Yao, Jianzhuang; Guo, Hong; Yang, Xiaohan

2015-08-01

Determining protein-protein interaction (PPI) in biological systems is of considerable importance, and prediction of PPI has become a popular research area. Although different classifiers have been developed for PPI prediction, no single classifier seems to be able to predict PPI with high confidence. We postulated that by combining individual classifiers the accuracy of PPI prediction could be improved. We developed a method called protein-protein interaction prediction classifiers merger (PPCM), and this method combines output from two PPI prediction tools, GO2PPI and Phyloprof, using Random Forests algorithm. The performance of PPCM was tested by area under the curve (AUC) using anmore » assembled Gold Standard database that contains both positive and negative PPI pairs. Our AUC test showed that PPCM significantly improved the PPI prediction accuracy over the corresponding individual classifiers. We found that additional classifiers incorporated into PPCM could lead to further improvement in the PPI prediction accuracy. Furthermore, cross species PPCM could achieve competitive and even better prediction accuracy compared to the single species PPCM. This study established a robust pipeline for PPI prediction by integrating multiple classifiers using Random Forests algorithm. Ultimately, this pipeline will be useful for predicting PPI in nonmodel species.« less

Reporting and appraising the context, process and impact of PPI on contributors, researchers and the trial during a randomised controlled trial - the 3D study.

PubMed

Mann, Cindy; Chilcott, Simon; Plumb, Katrina; Brooks, Edmund; Man, Mei-See

2018-01-01

Including patient and public involvement (PPI) in health research is thought to improve research but it is hard to be clear exactly how it helps. This is because PPI takes many forms, is sometimes only token and is not always reported clearly. This makes it difficult to combine the evidence so that clear conclusions can be reached about the ingredients of successful PPI and what PPI achieves. Previous research that has tried to combine the evidence has led to several guidelines for researchers to use in setting up and reporting PPI.This paper was written jointly by researchers and PPI contributors as a reflection on our experiences. The aim was to add to the evidence, by giving detail about the use of PPI in a large randomised controlled trial and the effect it had. We were guided by published PPI reporting guidelines. The effects on the trial are shown in a table of changes made because of suggestions from the PPI group. A survey was used to ask PPI contributors and researchers about their experience and effects they had noticed. Three themes were noted: impact on the trial, the effect of involvement on individual researchers and group members, and group environment. The PPI work affected the trial in many ways, including changes to documents used in the trial and advice on qualitative data collection methods and analysis. Individuals reported positive effects, including enjoying being in the group, gaining confidence, and learning how to share views. Patient and public involvement (PPI) is believed to enhance health care delivery research, and is widely required in research proposals. Detailed, standardised reporting of PPI is needed so that strategies to implement more than token PPI that achieves impact can be identified, properly evaluated and reproduced. Impact includes effects on the research, PPI contributors and researchers. Using contributor and researcher perspectives and drawing on published guidelines for reporting PPI, we aimed to reflect on our experience and contribute evidence relevant to two important questions: 'What difference does PPI make?' and 'What's the best way to do it?' Fourteen people living with multiple long-term conditions (multimorbidity) were PPI contributors to a randomised controlled trial to improve care for people with multimorbidity. Meetings took place approximately four times a year throughout the trial, beginning at grant application stage. Meeting notes were recorded and a log of PPI involvement was kept. At the end of the trial, seven PPI contributors and four researchers completed free-text questionnaires about their experience of PPI involvement and their perception of PPI impact. The responses were analysed thematically by two PPI contributors and one researcher. The PPI group proposed writing this report, which was co-authored by three PPI contributors and two researchers. Meeting attendance averaged nine PPI contributors and three to four researchers. The involvement log and meeting notes recorded a wide range of activities and impact including changes to participant documentation, advice on qualitative data collection, contribution to data analysis and dissemination advice. Three themes were identified from the questionnaires: impact on the study, including keeping the research grounded in patient experience; impact on individuals, including learning from group diversity and feeling valued; and an environment that facilitated participation. The size of the group influenced impact. Researchers and PPI contributors described a rewarding interaction that benefitted them and the research. PPI was wide-ranging and had impact on the trial, contributors and researchers. The group environment facilitated involvement. Feedback and group interactions benefitted individuals. The insights gained from this study will postitively influence the researchers' and contributors' future involvement with PPI.

PPI, paradoxes and Plato: who's sailing the ship?

PubMed

Ives, Jonathan; Damery, Sarah; Redwod, Sabi

2013-03-01

Over the last decade, patient and public involvement (PPI) has become a requisite in applied health research. Some funding bodies demand explicit evidence of PPI, while others have made a commitment to developing PPI in the projects they fund. Despite being commonplace, there remains a dearth of engagement with the ethical and theoretical underpinnings of PPI processes and practices. More specifically, while there is a small (but growing) body of literature examining the effectiveness and impact of PPI, there has been relatively little reflection on whether the concept/practice of PPI is internally coherent. Here, the authors unpick a 'paradox' within PPI, which highlights a tension between its moral and pragmatic motivations and its implementation. The authors argue that this 'professionalisation paradox' means we need to rethink the practice, and purpose, of PPI in research.

Weight ratio effects on morphology and electrocapacitive performance for the MoS2/polypyrrole electrodes

NASA Astrophysics Data System (ADS)

Tu, Chao-Chi; Peng, Pei-Wen; Lin, Lu-Yin

2018-06-01

MoS2 is one of the promising electroactive materials for charge-storage devices. The charges cannot only be stored in the intersheet of MoS2 and the intrasheet of individual atomic layers, but also can be accumulated by conducting the Faradaic reactions on the Mo center. To further enhance the electrocapacitive performance of MoS2, incorporating conducting polymers is one of the feasible ways to improve the connection between MoS2 nanosheets. At the same time, the growth of conducting polymers can also be controlled via incorporating MoS2 nanosheets in the synthesis to enhance the conductivity and increase the specific surface area of the conducting polymers. In this work, layered structures of MoS2 nanosheets are successfully synthesized via a simple hydrothermal method, and pyrrole monomers are oxidative polymerized in the MoS2 solution to prepare the nanocomposites with different ratios of MoS2 and polypyrrole (Ppy). The optimized MoS2/Ppy electrode shows a specific capacitance (CF) of 182.28 F/g, which is higher than those of the MoS2 (40.58 F/g) and Ppy (116.95 F/g) electrodes measured at the same scan rate of 10 mV/s. The excellent high-rate capacity and good cycling stability with 20% decay on the CF value comparing to the initial value after the 1000 times repeated charge/discharge process are also achieved for the optimized MoS2/Ppy electrode. The better performance for the MoS2/Ppy electrode is resulting from the larger surface area for charge accumulation and the enhanced interconnection networks for charge transportation. The results suggest that combining two materials with complementary properties as the electrocapacitive material is one of the attractive ways to realize efficient charge-storage devices with efficient electrochemical performances and good cycling lifes.

A little more conversation please? Qualitative study of researchers' and patients' interview accounts of training for patient and public involvement in clinical trials.

PubMed

Dudley, Louise; Gamble, Carrol; Allam, Alison; Bell, Philip; Buck, Deborah; Goodare, Heather; Hanley, Bec; Preston, Jennifer; Walker, Alison; Williamson, Paula; Young, Bridget

2015-04-27

Training in patient and public involvement (PPI) is recommended, yet little is known about what training is needed. We explored researchers' and PPI contributors' accounts of PPI activity and training to inform the design of PPI training for both parties. We used semi-structured qualitative interviews with researchers (chief investigators and trial managers) and PPI contributors, accessed through a cohort of clinical trials, which had been funded between 2006 and 2010. An analysis of transcripts of audio-recorded interviews drew on the constant comparative method. We interviewed 31 researchers and 17 PPI contributors from 28 trials. Most researchers could see some value in PPI training for researchers, although just under half had received such training themselves, and some had concerns about the purpose and evidence base for PPI training. PPI contributors were evenly split in their perceptions of whether researchers needed training in PPI. Few PPI contributors had themselves received training for their roles. Many informants across all groups felt that training PPI contributors was unnecessary because they already possessed the skills needed. Informants were also concerned that training would professionalise PPI contributors, limiting their ability to provide an authentic patient perspective. However, informants welcomed informal induction 'conversations' to help contributors understand their roles and support them in voicing their opinions. Informants believed that PPI contributors should be confident, motivated, intelligent, focussed on helping others and have relevant experience. Researchers looked for these qualities when selecting contributors, and spoke of how finding 'the right' contributor was more important than accessing 'the right' training. While informants were broadly receptive to PPI training for researchers, they expressed considerable reluctance to training PPI contributors. Providers of training will need to address these reservations. Our findings point to the importance of reconsidering how training is conceptualised, designed and promoted and of providing flexible, learning opportunities in ways that flow from researchers' and contributors' needs and preferences. We also identify some areas of training content and the need for further consideration to be given to the selection of PPI contributors and models for implementing PPI to ensure clinical trials benefit from a diversity of patient perspectives.

PPI layouts: BioJS components for the display of Protein-Protein Interactions.

PubMed

Salazar, Gustavo A; Meintjes, Ayton; Mulder, Nicola

2014-01-01

We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753.

Proton pump inhibitors increase the incidence of bone fractures in hepatitis C patients.

PubMed

Mello, Michael; Weideman, Rick A; Little, Bertis B; Weideman, Mark W; Cryer, Byron; Brown, Geri R

2012-09-01

While proton pump inhibitors (PPI) may increase the risk of bone fractures, the incidence of new bone fractures in a chronic hepatitis C virus (HCV) infected cohort, with or without PPI exposure, has not been explored. A retrospective cohort study of the incidence of bone fractures over 10 years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C Registry was performed. The study endpoint was the incidence of verified new bone fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI use was defined as those taking a PPI for ≥360 days. Pt-yrs of exposure for PPI users began on the first PPI prescription date, and pt-yrs of exposure for non-PPI users began with first date of any non-PPI prescription. For both HCV groups, the final date of patients' study duration was defined by end of PPI exposure, bone fracture occurrence, death or end of study evaluation period. Exclusion criteria included use of bone health modifying medications ≥30 days. Statistical differences in fracture incidence between groups were determined by multivariate regression analysis. Among the total study population analyzed (n = 2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were 13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively. The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p < 0.001) in PPI users. In patients with chronic HCV, use of PPI for >1 year increased the risk of new bone fractures by more than threefold.

Proton Pump Inhibitor-Responsive Oesophageal Eosinophilia: An Entity Challenging Current Diagnostic Criteria for Eosinophilic Oesophagitis

PubMed Central

Molina-Infante, Javier; Bredenoord, Albert J.; Cheng, Edaire; Dellon, Evan S.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Katzka, David A.; Moawad, Fouad J.; Rothenberg, Marc E.; Schoepfer, Alain; Spechler, Stuart; Wen, Ting; Straumann, Alex; Lucendo, Alfredo J.

2016-01-01

Consensus diagnostic recommendations to distinguish gastro-oesophageal reflux disease (GORD) from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPI) unexpectedly uncovered an entity called “PPI-responsive oesophageal eosinophilia” (PPI-REE). PPI-REE refers to patients with clinical and histologic features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that PPI-REE and EoE patients at baseline are clinically, endoscopically and histologically indistinguishable, and have significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in PPI-REE patients, similar to the effects of topical steroids in EoE patients. Additionally, recent series have reported that EoE patients responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunologic mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic, and therapeutic features cannot be reliably distinguished. For patients with symptoms and histologic features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment, before diet and topical steroids. The reasons why some EoE patients respond to PPI, while others do not, remain to be elucidated. PMID:26685124

Preparation of Different Substitued Polypyridine Ligands, Ruthenium(II)-Bridged Complexes and Spectoscopıc Studies.

PubMed

Obali, Aslihan Yilmaz; Ucan, Halil Ismet

2016-09-01

Novel different substitued polypyridine ligands 4-((4-(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)phenoxy)methyl)benzaldehyde (BA-PPY), (E)-N-(4-((4-(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)phenoxy)methyl)benzylidene)-pyrene-4-amine (PR-PPY), (E)-N-(4-((4-(1H-imidazo[4,5-f][1,10] phenanthroline-2-yl)phenoxy)methyl)benzylidene)-1,10-phenanthroline-5amine (FN-PPY), 2-(4-(bromomethyl)phenyl)-1H-imidazo[4,5-f][1,10] phenanthroline (BR-PPY), 2-(4-(azidomethyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (N3-PPY) and triazole containing polypyridine ligand 3,4-bis[(4-(metoxy)-1,2,3-triazole)1-methylphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)] benzaldehyde (BA-DIPPY) and Ruthenium(II) complexes were synthesized and characterized. Their photopysical properties were investigated. The complexes RuP(PR-PPY), RuB(PR-PPY, RuP(FN-PPY) and RuB(FN-PPY) exhibited a broad absorption bands at 485, 475, 476, and 453 nm, respectively, assignable to the spin-allowed MLCT (dπ-π*) transition. The emission maxima of the pyrene-appended polypyridine ligand PR-PPY was observed at λems = 616 nm and the phenanthroline-appended polypyridine ligand FN-PPY was observed at λems = 668 nm. And the emission maxima of the complexes RuP(PR-PPY), RuB(PR-PPY), RuP(FN-PPY) and RuB(FN-PPY) were observed at λems = 646, 646, 685 and 685 nm, respectively. As seen in fluorescence spectra, the fluorescence intensities of the ligands are higher than their metal complexes. This is because of quenching effect of Ruthenium(II) metal on chromophore groups.

Registration of immunoglobuline AB/AG reaction with planar polarization interferometer

NASA Astrophysics Data System (ADS)

Nabok, Alexei V.; Starodub, Nickolaj F.; Ray, Asim K.; Hassan, Aseel K.

2000-12-01

Immobilization of human immunoglobuline (IgG) (AG) and goat on human IGG antibodies (AB) as well as AB/AG specific reaction were studied with planar polarization interferometry (PPI). In this novel method, polarized laser beam was coupled into the planar waveguide made on silicon wafer and consisted of 20nm Si3N4 layer sandwiched between two 1.5 micrometers SiO2 layers with the sensing window etched in the top SIO2 layer. One of the immune components was deposited by means of polyelectrolyte self- assembly on top of the Si3N3 layer within the sensing window, P-component of the polarized light is sensitive to adsorption, while s-component serves as a reference. Thus the outcoming light intensity depends on the phase shift between s- and p-components. Different sequences of immobilization of the immune components were studied with both surface plasmon resonance (SPR) and PPI methods. It was shown that predeposition of a monolayer of protein A, which is believed to affect the orientation of the immune components, causes an additional increase in the sensitivity. PPI method allowed us to improve substantially the sensitivity towards AB/AG reaction as compared to traditional SPR method. Particularly, of specific binding of 3ng/ml AG was registered.

Identification of key genes related to high-risk gastrointestinal stromal tumors using bioinformatics analysis.

PubMed

Jin, Shuan; Zhu, Wenhua; Li, Jun

2018-01-01

The purpose of this study was to identify predictive biomarkers used for clinical therapy and prognostic evaluation of high-risk gastrointestinal stromal tumors (GISTs). In this study, microarray data GSE31802 were used to identify differentially expressed genes (DEGs) between high-risk GISTs and low-risk GISTs. Then, enrichment analysis of DEGs was conducted based on the gene ontology and kyoto encyclopedia of genes and genomes pathway database. In addition, the transcription factors and cancer-related genes in DEGs were screened according to the TRANSFAC, TSGene, and TAG database. Finally, protein-protein interaction (PPI) network was constructed and analyzed to look for critical genes involved in high-risk GISTs. A total of forty DEGs were obtained and these genes were mainly involved in four pathways, including melanogenesis, neuroactive ligand-receptor interaction, malaria, and hematopoietic cell lineage. The enriched biological processes were related to the regulation of insulin secretion, integrin activation, and neuropeptide signaling pathway. Transcription factor analysis of DEGs indicated that POU domain, class 2, associating factor 1 (POU2AF1) was significantly downregulated in high-risk GISTs. By constructing the PPI network of DEGs, ten genes with high degrees formed local networks, such as PNOC, P2RY14, and SELP. Four genes as POU2AF1, PNOC, P2RY14, and SELP might be used as biomarkers for prognosis of high-risk GISTs.

Identification of genes related to proliferative diabetic retinopathy through RWR algorithm based on protein-protein interaction network.

PubMed

Zhang, Jian; Suo, Yan; Liu, Min; Xu, Xun

2018-06-01

Proliferative diabetic retinopathy (PDR) is one of the most common complications of diabetes and can lead to blindness. Proteomic studies have provided insight into the pathogenesis of PDR and a series of PDR-related genes has been identified but are far from fully characterized because the experimental methods are expensive and time consuming. In our previous study, we successfully identified 35 candidate PDR-related genes through the shortest-path algorithm. In the current study, we developed a computational method using the random walk with restart (RWR) algorithm and the protein-protein interaction (PPI) network to identify potential PDR-related genes. After some possible genes were obtained by the RWR algorithm, a three-stage filtration strategy, which includes the permutation test, interaction test and enrichment test, was applied to exclude potential false positives caused by the structure of PPI network, the poor interaction strength, and the limited similarity on gene ontology (GO) terms and biological pathways. As a result, 36 candidate genes were discovered by the method which was different from the 35 genes reported in our previous study. A literature review showed that 21 of these 36 genes are supported by previous experiments. These findings suggest the robustness and complementary effects of both our efforts using different computational methods, thus providing an alternative method to study PDR pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.

PubMed

Sable, Rushikesh; Jois, Seetharama

2015-06-23

Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

Large-scale protein-protein interactions detection by integrating big biosensing data with computational model.

PubMed

You, Zhu-Hong; Li, Shuai; Gao, Xin; Luo, Xin; Ji, Zhen

2014-01-01

Protein-protein interactions are the basis of biological functions, and studying these interactions on a molecular level is of crucial importance for understanding the functionality of a living cell. During the past decade, biosensors have emerged as an important tool for the high-throughput identification of proteins and their interactions. However, the high-throughput experimental methods for identifying PPIs are both time-consuming and expensive. On the other hand, high-throughput PPI data are often associated with high false-positive and high false-negative rates. Targeting at these problems, we propose a method for PPI detection by integrating biosensor-based PPI data with a novel computational model. This method was developed based on the algorithm of extreme learning machine combined with a novel representation of protein sequence descriptor. When performed on the large-scale human protein interaction dataset, the proposed method achieved 84.8% prediction accuracy with 84.08% sensitivity at the specificity of 85.53%. We conducted more extensive experiments to compare the proposed method with the state-of-the-art techniques, support vector machine. The achieved results demonstrate that our approach is very promising for detecting new PPIs, and it can be a helpful supplement for biosensor-based PPI data detection.

What Difference Does Patient and Public Involvement Make and What Are Its Pathways to Impact? Qualitative Study of Patients and Researchers from a Cohort of Randomised Clinical Trials

PubMed Central

Dudley, Louise; Gamble, Carrol; Preston, Jennifer; Buck, Deborah; Hanley, Bec; Williamson, Paula; Young, Bridget

2015-01-01

Background Patient and public involvement (PPI) is advocated in clinical trials yet evidence on how to optimise its impact is limited. We explored researchers' and PPI contributors' accounts of the impact of PPI within trials and factors likely to influence its impact. Methods Semi-structured qualitative interviews with researchers and PPI contributors accessed through a cohort of randomised clinical trials. Analysis of transcripts of audio-recorded interviews was informed by the principles of the constant comparative method, elements of content analysis and informant triangulation. Results We interviewed 21 chief investigators, 10 trial managers and 17 PPI contributors from 28 trials. The accounts of informants within the same trials were largely in agreement. Over half the informants indicted PPI had made a difference within a trial, through contributions that influenced either an aspect of a trial, or how researchers thought about a trial. According to informants, the opportunity for PPI to make a difference was influenced by two main factors: whether chief investigators had goals and plans for PPI and the quality of the relationship between the research team and the PPI contributors. Early involvement of PPI contributors and including them in responsive (e.g. advisory groups) and managerial (e.g. trial management groups) roles were more likely to achieve impact compared to late involvement and oversight roles (e.g. trial steering committees). Conclusion Those seeking to enhance PPI in trials should develop goals for PPI at an early stage that fits the needs of the trial, plan PPI implementation in accordance with these goals, invest in developing good relationships between PPI contributors and researchers, and favour responsive and managerial roles for contributors in preference to oversight-only roles. These features could be used by research funders in judging PPI in trial grant applications and to inform policies to optimise PPI within trials. PMID:26053063

Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity.

PubMed

Molina-Infante, Javier; Katzka, David A; Dellon, Evan S

2015-01-01

Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease, first described in 1993, with a steadily increasing incidence and prevalence in western countries. Over the 80's and early 90's, dense esophageal eosinophilia was mostly associated gastroesophageal reflux disease (GERD). For the next 15 years, EoE and GERD were rigidly considered separate entities: Esophageal eosinophilia with pathological acid exposure on pH monitoring or response to proton pump inhibitor (PPI) therapy was GERD, whereas normal pH monitoring or absence of response to PPIs was EoE. Updated guidelines in 2011 described a novel phenotype, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), referring to patients who appear to have EoE clinically, but who achieve complete remission after PPI therapy. Currently, PPI-REE must be formally excluded before diagnosing EoE, since 30-40% of patients with suspected EoE are eventually diagnosed with PPI-REE.Interestingly, PPI-REE and EoE remain undistinguishable based on clinical, endoscopic, and histological findings, pH monitoring, and measurement of tissue markers and cytokines related to eosinophilic inflammation.This review article aims to revisit the relatively novel concept of PPI-REE from a historical perspective, given the strong belief that only GERD, as an acid peptic disorder, could respond to the acid suppressing ability of PPI therapy, is becoming outdated. Evolving evidence suggests that PPI-REE is genetically and phenotypically undistinguishable from EoE and PPI therapy alone can almost completely reverse allergic inflammation. As such, PPI-REE might constitute a subphenotype of EoE and PPI therapy may be the first therapeutic step and diet/ steroids may represent step up therapy. Possibly, the term PPI-REE will be soon replaced by PPI-responsive EoE. The mechanism as to why some patients respond to PPI therapy (PPI-REE) while others do not (EoE), remains to be elucidated.

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

Computational prediction of host-pathogen protein-protein interactions.

PubMed

Dyer, Matthew D; Murali, T M; Sobral, Bruno W

2007-07-01

Infectious diseases such as malaria result in millions of deaths each year. An important aspect of any host-pathogen system is the mechanism by which a pathogen can infect its host. One method of infection is via protein-protein interactions (PPIs) where pathogen proteins target host proteins. Developing computational methods that identify which PPIs enable a pathogen to infect a host has great implications in identifying potential targets for therapeutics. We present a method that integrates known intra-species PPIs with protein-domain profiles to predict PPIs between host and pathogen proteins. Given a set of intra-species PPIs, we identify the functional domains in each of the interacting proteins. For every pair of functional domains, we use Bayesian statistics to assess the probability that two proteins with that pair of domains will interact. We apply our method to the Homo sapiens-Plasmodium falciparum host-pathogen system. Our system predicts 516 PPIs between proteins from these two organisms. We show that pairs of human proteins we predict to interact with the same Plasmodium protein are close to each other in the human PPI network and that Plasmodium pairs predicted to interact with same human protein are co-expressed in DNA microarray datasets measured during various stages of the Plasmodium life cycle. Finally, we identify functionally enriched sub-networks spanned by the predicted interactions and discuss the plausibility of our predictions. Supplementary data are available at http://staff.vbi.vt.edu/dyermd/publications/dyer2007a.html. Supplementary data are available at Bioinformatics online.

How perfect can protein interactomes be?

PubMed

Levy, Emmanuel D; Landry, Christian R; Michnick, Stephen W

2009-03-03

Any engineered device should certainly not contain nonfunctional components, for this would be a waste of energy and money. In contrast, evolutionary theory tells us that biological systems need not be optimized and may very well accumulate nonfunctional elements. Mutational and demographic processes contribute to the cluttering of eukaryotic genomes and transcriptional networks with "junk" DNA and spurious DNA binding sites. Here, we question whether such a notion should be applied to protein interactomes-that is, whether these protein interactomes are expected to contain a fraction of nonselected, nonfunctional protein-protein interactions (PPIs), which we term "noisy." We propose a simple relationship between the fraction of noisy interactions expected in a given organism and three parameters: (i) the number of mutations needed to create and destroy interactions, (ii) the size of the proteome, and (iii) the fitness cost of noisy interactions. All three parameters suggest that noisy PPIs are expected to exist. Their existence could help to explain why PPIs determined from large-scale studies often lack functional relationships between interacting proteins, why PPIs are poorly conserved across organisms, and why the PPI space appears to be immensely large. Finally, we propose experimental strategies to estimate the fraction of evolutionary noise in PPI networks.

Value of the Gastroesophageal Reflux Disease Questionnaire (GerdQ) in predicting the proton pump inhibitor response in coronary artery disease patients with gastroesophageal reflux-related chest pain.

PubMed

He, S; Liu, Y; Chen, Y; Tang, Y; Xu, J; Tang, C

2016-05-01

Chest pain experienced by patients with coronary artery disease can be partly due to gastroesophageal reflux-induced chest pain (GERP). Empirical proton pump inhibitor (PPI) therapy has been recommended as an initial clinical approach for treating GERP. However, PPI use may lead to some health problems. The Gastroesophageal Reflux Disease Questionnaire (GerdQ) may represent a noninvasive and cost-effective approach for avoiding PPI misuse and for identifying the appropriate patients for the PPI trial test. The aim of this pilot study was to prospectively evaluate the association between GerdQ scores and PPI response in patients with coronary artery disease (CAD) and GERP to determine whether the GerdQ predicts the PPI response in patients with CAD and GERP and to further validate the clinical application value of the GerdQ. A total of 154 consecutive patients with potential GERP were recruited to complete a GerdQ with subsequent PPI therapy. Based on the PPI trial result, patients were divided into a PPI-positive response group and a PPI-negative response group. The difference in the GerdQ scores between the two groups was assessed. The receiver operating characteristic (ROC) curve of GerdQ score was drawn according to the PPI response as the gold standard. The ability of GerdQ to predict the PPI response was assessed. A total of 96 patients completed the entire study; 62 patients (64.6%) were assigned to the PPI-positive response group, and 34 patients (35.4%) to the PPI-negative response group. The GerdQ score of the PPI-positive response group (8.11 ± 3.315) was significantly higher than that of the PPI-negative response group (4.41 ± 2.743), and the difference was statistically significant (t = 5.863, P = 0.000). The ROC curve was drawn according to a PPI response assessment result with a score above 2 as the gold standard. The area under curve was 0.806. When the critical value of GerdQ score was 7.5, Youden index was up to 0.514, the diagnostic sensitivity was 0.661, and the diagnostic specificity was 0.853. A GerdQ score greater than 7.5 better predicts the response to the PPI trial therapy. There is a strong association between the GerdQ score and the response to PPI therapy. Higher GerdQ scores were predictive of a positive PPI response in CAD patients with GERP. The GerdQ may be a reasonable screening tool for GERP in patients with CAD who are prepared to accept PPI therapy. © 2015 International Society for Diseases of the Esophagus.

Modular biological function is most effectively captured by combining molecular interaction data types.

PubMed

Ames, Ryan M; Macpherson, Jamie I; Pinney, John W; Lovell, Simon C; Robertson, David L

2013-01-01

Large-scale molecular interaction data sets have the potential to provide a comprehensive, system-wide understanding of biological function. Although individual molecules can be promiscuous in terms of their contribution to function, molecular functions emerge from the specific interactions of molecules giving rise to modular organisation. As functions often derive from a range of mechanisms, we demonstrate that they are best studied using networks derived from different sources. Implementing a graph partitioning algorithm we identify subnetworks in yeast protein-protein interaction (PPI), genetic interaction and gene co-regulation networks. Among these subnetworks we identify cohesive subgraphs that we expect to represent functional modules in the different data types. We demonstrate significant overlap between the subgraphs generated from the different data types and show these overlaps can represent related functions as represented by the Gene Ontology (GO). Next, we investigate the correspondence between our subgraphs and the Gene Ontology. This revealed varying degrees of coverage of the biological process, molecular function and cellular component ontologies, dependent on the data type. For example, subgraphs from the PPI show enrichment for 84%, 58% and 93% of annotated GO terms, respectively. Integrating the interaction data into a combined network increases the coverage of GO. Furthermore, the different annotation types of GO are not predominantly associated with one of the interaction data types. Collectively our results demonstrate that successful capture of functional relationships by network data depends on both the specific biological function being characterised and the type of network data being used. We identify functions that require integrated information to be accurately represented, demonstrating the limitations of individual data types. Combining interaction subnetworks across data types is therefore essential for fully understanding the complex and emergent nature of biological function.

Identification of hub subnetwork based on topological features of genes in breast cancer

PubMed Central

ZHUANG, DA-YONG; JIANG, LI; HE, QING-QING; ZHOU, PENG; YUE, TAO

2015-01-01

The aim of this study was to provide functional insight into the identification of hub subnetworks by aggregating the behavior of genes connected in a protein-protein interaction (PPI) network. We applied a protein network-based approach to identify subnetworks which may provide new insight into the functions of pathways involved in breast cancer rather than individual genes. Five groups of breast cancer data were downloaded and analyzed from the Gene Expression Omnibus (GEO) database of high-throughput gene expression data to identify gene signatures using the genome-wide global significance (GWGS) method. A PPI network was constructed using Cytoscape and clusters that focused on highly connected nodes were obtained using the molecular complex detection (MCODE) clustering algorithm. Pathway analysis was performed to assess the functional relevance of selected gene signatures based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Topological centrality was used to characterize the biological importance of gene signatures, pathways and clusters. The results revealed that, cluster1, as well as the cell cycle and oocyte meiosis pathways were significant subnetworks in the analysis of degree and other centralities, in which hub nodes mostly distributed. The most important hub nodes, with top ranked centrality, were also similar with the common genes from the above three subnetwork intersections, which was viewed as a hub subnetwork with more reproducible than individual critical genes selected without network information. This hub subnetwork attributed to the same biological process which was essential in the function of cell growth and death. This increased the accuracy of identifying gene interactions that took place within the same functional process and was potentially useful for the development of biomarkers and networks for breast cancer. PMID:25573623

Default Mode Network (DMN) Deactivation during Odor-Visual Association

PubMed Central

Karunanayaka, Prasanna R.; Wilson, Donald A.; Tobia, Michael J.; Martinez, Brittany; Meadowcroft, Mark; Eslinger, Paul J.; Yang, Qing X.

2017-01-01

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, we investigated the DMN’s role during olfactory processing using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26±4 yrs., 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor+visual and visual-only trial conditions. During odor+visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the 29 participants (mean age = 27.0 ± 6.0 yrs.,11 females) also took part in a control no-odor fMRI paradigm that consisted of visual-only trial conditions which were identical to the visual-only trials in the odor-visual association paradigm. We used Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor+visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor+visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights DMN’s role in task-evoked brain activity and behavioral responses during olfactory processing. PMID:27785847

Identification of key candidate genes and pathways in hepatitis B virus-associated acute liver failure by bioinformatical analysis

PubMed Central

Lin, Huapeng; Zhang, Qian; Li, Xiaocheng; Wu, Yushen; Liu, Ye; Hu, Yingchun

2018-01-01

Abstract Hepatitis B virus-associated acute liver failure (HBV-ALF) is a rare but life-threatening syndrome that carried a high morbidity and mortality. Our study aimed to explore the possible molecular mechanisms of HBV-ALF by means of bioinformatics analysis. In this study, genes expression microarray datasets of HBV-ALF from Gene Expression Omnibus were collected, and then we identified differentially expressed genes (DEGs) by the limma package in R. After functional enrichment analysis, we constructed the protein–protein interaction (PPI) network by the Search Tool for the Retrieval of Interacting Genes online database and weighted genes coexpression network by the WGCNA package in R. Subsequently, we picked out the hub genes among the DEGs. A total of 423 DEGs with 198 upregulated genes and 225 downregulated genes were identified between HBV-ALF and normal samples. The upregulated genes were mainly enriched in immune response, and the downregulated genes were mainly enriched in complement and coagulation cascades. Orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), plasminogen (PLG), and aldehyde oxidase 1 (AOX1) were picked out as the hub genes that with a high degree in both PPI network and weighted genes coexpression network. The weighted genes coexpression network analysis found out 3 of the 5 modules that upregulated genes enriched in were closely related to immune system. The downregulated genes enriched in only one module, and the genes in this module majorly enriched in the complement and coagulation cascades pathway. In conclusion, 4 genes (ORM1, ORM2, PLG, and AOX1) with immune response and the complement and coagulation cascades pathway may take part in the pathogenesis of HBV-ALF, and these candidate genes and pathways could be therapeutic targets for HBV-ALF. PMID:29384847

Development of a sensor prepared by entrapment of MIP particles in electrosynthesised polymer films for electrochemical detection of ephedrine.

PubMed

Mazzotta, E; Picca, R A; Malitesta, C; Piletsky, S A; Piletska, E V

2008-02-28

A voltammetric sensor for (-)-ephedrine has been prepared by a novel approach based on immobilisation of an imprinted polymer for ephedrine (MIPE) in an electrosynthesised polypyrrole (PPY) film. Composite films were grown potentiostatically at 1.0 V vs. Pt (QRE) on a glassy carbon electrode using an unconventional "upside-down" (UD) geometry for the three-electrode cell. As a consequence, a high MIP loading was obtained, as revealed by SEM. The sensor response was evaluated, after overoxidation of PPY matrix, by cyclic voltammetry after pre-concentration in a buffered solution of analyte in 0.5-3 mM concentration range. An ephedrine peak at approximately 0.9 V increasing with concentration and saturating at high concentrations was evident. PPY-modified electrode showed a response, which was distinctly lower than the MIP response for the same concentration of the template. The effect of potential interferences including compounds usually found in human fluids (ascorbic acid, uric acid, urea, glucose, sorbitol, glycine, dopamine) was examined.

Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces.

PubMed

Engin, H Billur; Kreisberg, Jason F; Carter, Hannah

2016-01-01

Recently it has been shown that cancer mutations selectively target protein-protein interactions. We hypothesized that mutations affecting distinct protein interactions involving established cancer genes could contribute to tumor heterogeneity, and that novel mechanistic insights might be gained into tumorigenesis by investigating protein interactions under positive selection in cancer. To identify protein interactions under positive selection in cancer, we mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896 experimentally determined protein structures and analyzed their spatial distribution. In total, 20% of mutations on the surface of known cancer genes perturbed protein-protein interactions (PPIs), and this enrichment for PPI interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value < 10(-4)) and oncogenes (Odds Ratio 1.17, P-value < 10(-3)). To study this further, we constructed a bipartite network representing structurally resolved PPIs from all available human complexes in the Protein Data Bank (2,864 proteins, 3,072 PPIs). Analysis of frequently mutated cancer genes within this network revealed that tumor-suppressors, but not oncogenes, are significantly enriched with functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value < 10(-8)). We present two important examples, TP53 and beta-2-microglobulin, for which the patterns of somatic mutations at interfaces provide insights into specifically perturbed biological circuits. In patients with TP53 mutations, patient survival correlated with the specific interactions that were perturbed. Moreover, we investigated mutations at the interface of protein-nucleotide interactions and observed an unexpected number of missense mutations but not silent mutations occurring within DNA and RNA binding sites. Finally, we provide a resource of 3,072 PPI interfaces ranked according to their mutation rates. Analysis of this list highlights 282 novel candidate cancer genes that encode proteins participating in interactions that are perturbed recurrently across tumors. In summary, mutation of specific protein interactions is an important contributor to tumor heterogeneity and may have important implications for clinical outcomes.

BioPlex Display: An Interactive Suite for Large-Scale AP-MS Protein-Protein Interaction Data.

PubMed

Schweppe, Devin K; Huttlin, Edward L; Harper, J Wade; Gygi, Steven P

2018-01-05

The development of large-scale data sets requires a new means to display and disseminate research studies to large audiences. Knowledge of protein-protein interaction (PPI) networks has become a principle interest of many groups within the field of proteomics. At the confluence of technologies, such as cross-linking mass spectrometry, yeast two-hybrid, protein cofractionation, and affinity purification mass spectrometry (AP-MS), detection of PPIs can uncover novel biological inferences at a high-throughput. Thus new platforms to provide community access to large data sets are necessary. To this end, we have developed a web application that enables exploration and dissemination of the growing BioPlex interaction network. BioPlex is a large-scale interactome data set based on AP-MS of baits from the human ORFeome. The latest BioPlex data set release (BioPlex 2.0) contains 56 553 interactions from 5891 AP-MS experiments. To improve community access to this vast compendium of interactions, we developed BioPlex Display, which integrates individual protein querying, access to empirical data, and on-the-fly annotation of networks within an easy-to-use and mobile web application. BioPlex Display enables rapid acquisition of data from BioPlex and development of hypotheses based on protein interactions.

Proton pump inhibitor co-prescription with dual antiplatelet therapy among patients with acute coronary syndrome in Qatar.

PubMed

Awaisu, Ahmed; Hamou, Fatima; Mekideche, Lylia; El Muabby, Nisrine; Mahfouz, Ahmed; Mohammed, Shaban; Saad, Ahmad

2016-04-01

There are increasing concerns about clinically significant interactions between proton pump inhibitors (PPIs) and clopidogrel, resulting in adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). However, published evidence on the prevalence and predictors of PPI use with dual antiplatelet therapy (DAPT) is scarce. This study investigated the prevalence of PPI use among patients with ACS receiving DAPT and possible predictors of co-prescribing the PPIs with the DAPT. Heart Hospital, a specialized tertiary care center in Qatar. A retrospective observational study of a prescription database was conducted. Subjects included 626 patients admitted between January and December 2012 with the diagnosis of ACS who received DAPT and discharged with or without a PPI. Univariate analysis and multivariate binary logistic regression analysis were performed to determine the predictors of PPI-DAPT co-prescription. Prevalence of PPI co-prescribing with DAPT in proportions and percentages and odd ratios for the predictors of PPI-DAPT co-prescribing. A total of 626 patients were analyzed for PPI prevalence, with 200 patients (32 %) being prescribed PPI with DAPT upon discharge. After controlling for confounders, PPI use on admission (aOR 14.5; 95 % CI 7.6-27.6, p < 0.001), nationality (aOR 3.2; 95 % CI 1.1-9.9, p = 0.041), and having a history of diabetes (aOR 0.5; 95 % CI 0.24-0.99, p = 0.046) significantly influenced PPI-DAPT co-prescribing. Users of PPI on admission compared to nonusers were about 15 times more likely to be prescribed PPI with DAPT upon discharge; likewise, having Qatari nationality increased the likelihood of co-prescribing PPI with DAPT upon discharge by three folds. Lastly, patients with a history of diabetes were 50 % less likely to be prescribed PPIs upon discharge compared to those with no history of diabetes. The rate of PPI co-prescribing with DAPT in the population studied was relatively high. The strongest predictor of PPI co-prescription with DAPT upon discharge was PPI use on admission. Furthermore, PPI prescribing was significantly predicted by nationality and not having diabetes. Further studies are warranted to better predict the factors associated with PPI-DAPT co-prescription and to investigate rational prescribing of PPIs among ACS patients.

Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients

PubMed Central

Paroni Sterbini, Francesco; Palladini, Alessandra; Masucci, Luca; Cannistraci, Carlo Vittorio; Pastorino, Roberta; Ianiro, Gianluca; Bugli, Francesca; Martini, Cecilia; Ricciardi, Walter; Gasbarrini, Antonio; Cammarota, Giovanni; Posteraro, Brunella

2016-01-01

ABSTRACT Besides being part of anti-Helicobacter pylori treatment regimens, proton pump inhibitors (PPIs) are increasingly being used to treat dyspepsia. However, little is known about the effects of PPIs on the human gastric microbiota, especially those related to H. pylori infection. The goal of this study was to characterize the stomach microbial communities in patients with dyspepsia and to investigate their relationships with PPI use and H. pylori status. Using 16S rRNA gene pyrosequencing, we analyzed the mucosa-associated microbial populations of 24 patients, of whom 12 were treated with the PPI omeprazole and 9 (5 treated and 4 untreated) were positive for H. pylori infection. The Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria phyla accounted for 98% of all of the sequences, with Helicobacter, Streptococcus, and Prevotella ranking among the 10 most abundant genera. H. pylori infection or PPI treatment did not significantly influence gastric microbial species composition in dyspeptic patients. Principal-coordinate analysis of weighted UniFrac distances in these communities revealed clear but significant separation according to H. pylori status only. However, in PPI-treated patients, Firmicutes, particularly Streptococcaceae, were significantly increased in relative abundance compared to those in untreated patients. Consistently, Streptococcus was also found to significantly increase in relation to PPI treatment, and this increase seemed to occur independently of H. pylori infection. Our results suggest that Streptococcus may be a key indicator of PPI-induced gastric microbial composition changes in dyspeptic patients. Whether the gastric microbiota alteration contributes to dyspepsia needs further investigation. IMPORTANCE Although PPIs have become a popular treatment choice, a growing number of dyspeptic patients may be treated unnecessarily. We found that patients treated with omeprazole showed gastric microbial communities that were different from those of untreated patients. These differences regarded the abundances of specific taxa. By understanding the relationships between PPIs and members of the gastric microbiota, it will be possible to envisage new strategies for better managing patients with dyspepsia. PMID:27590821

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

PubMed

Lin, C-Y; Wang, C-W; Hui, C-Y R; Chang, Y-C; Yang, C-H; Cheng, C-Y; Chen, W-W; Ke, W-M; Chung, W-H

2018-01-01

Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials - a work in progress.

PubMed

Bagley, Heather J; Short, Hannah; Harman, Nicola L; Hickey, Helen R; Gamble, Carrol L; Woolfall, Kerry; Young, Bridget; Williamson, Paula R

2016-01-01

Funders of research are increasingly requiring researchers to involve patients and the public in their research. Patient and public involvement (PPI) in research can potentially help researchers make sure that the design of their research is relevant, that it is participant friendly and ethically sound. Using and sharing PPI resources can benefit those involved in undertaking PPI, but existing PPI resources are not used consistently and this can lead to duplication of effort. This paper describes how we are developing a toolkit to support clinical trials teams in a clinical trials unit. The toolkit will provide a key 'off the shelf' resource to support trial teams with limited resources, in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: ● listen to the views and experience of both research teams and patient and public contributors who use the tools; ● modify the tools based on our experience of using them; ● identify the need for future tools; ● update the toolkit based on any newly identified resources that come to light; ● raise awareness of the toolkit and ● work in collaboration with others to either develop or test out PPI resources in order to reduce duplication of work in PPI. Background Patient and public involvement (PPI) in research is increasingly a funder requirement due to the potential benefits in the design of relevant, participant friendly, ethically sound research. The use and sharing of resources can benefit PPI, but available resources are not consistently used leading to duplication of effort. This paper describes a developing toolkit to support clinical trials teams to undertake effective and meaningful PPI. Methods The first phase in developing the toolkit was to describe which PPI activities should be considered in the pathway of a clinical trial and at what stage these activities should take place. This pathway was informed through review of the type and timing of PPI activities within trials coordinated by the Clinical Trials Research Centre and previously described areas of potential PPI impact in trials. In the second phase, key websites around PPI and identification of resources opportunistically, e.g. in conversation with other trialists or social media, were used to identify resources. Tools were developed where gaps existed. Results A flowchart was developed describing PPI activities that should be considered in the clinical trial pathway and the point at which these activities should happen. Three toolkit domains were identified: planning PPI; supporting PPI; recording and evaluating PPI. Four main activities and corresponding tools were identified under the planning for PPI: developing a plan; identifying patient and public contributors; allocating appropriate costs; and managing expectations. In supporting PPI, tools were developed to review participant information sheets. These tools, which require a summary of potential trial participant characteristics and circumstances help to clarify requirements and expectations of PPI review. For recording and evaluating PPI, the planned PPI interventions should be monitored in terms of impact, and a tool to monitor public contributor experience is in development. Conclusions This toolkit provides a developing 'off the shelf' resource to support trial teams with limited resources in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: listen to the views and experience of both research teams and public contributors using the tools, to identify the need for future tools, to modify tools based on experience of their use; to update the toolkit based on any newly identified resources that come to light; to raise awareness of the toolkit and to work in collaboration with others to both develop and test out PPI resources in order to reduce duplication of work in PPI.

The role of emotion regulation in the relations between psychopathy factors and impulsive and premeditated aggression.

PubMed

Long, Katherine; Felton, Julia W; Lilienfeld, Scott O; Lejuez, Carl W

2014-10-01

Given the high rates of aggressive behavior among highly psychopathic individuals, much research has sought to clarify the nature of the relation between psychopathy and aggression. The present study examined relations between Fearless Dominance (PPI FD), Self-Centered Impulsivity (PPI SCI), and Coldheartedness (PPI CH) Factors of the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996) and aggression dimensions (premeditated and impulsive aggression) in a sample of substance users receiving inpatient treatment. At the univariate level, PPI FD traits were significantly and positively related to premeditated aggression, but were not significantly related to impulsive aggression. PPI SCI traits were positively related to both forms of aggression, whereas PPI CH was not significantly related to either aggression dimension. Emotion regulation difficulties, as measured by the Difficulties with Emotion Regulation Scale (DERS; Gratz & Roemer, 2004), were negatively related to PPI FD traits, positively related to PPI SCI traits, and negatively related to PPI CH traits. Both PPI SCI and PPI FD traits exerted significant indirect effects on impulsive aggression through the DERS. In contrast, the DERS did not mediate the relations between psychopathic traits and premeditated aggression. Results provide a more nuanced understanding of the psychopathy-aggression relations and suggest that difficulties with emotion regulation may be an important mediator of the relations between psychopathy factors and impulsive aggression. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The Role of Emotion Regulation in the Relations between Psychopathy Factors and Impulsive and Premeditated Aggression

PubMed Central

Long, Katherine; Felton, Julia W.; Lilienfeld, Scott O.; Lejuez, Carl W.

2014-01-01

Given the high rates of aggressive behavior among highly psychopathic individuals, much research has sought to clarify the nature of the relation between psychopathy and aggression. The present study examined relations between Fearless Dominance (PPI FD), Self-Centered Impulsivity (PPI SCI), and Coldheartedness (PPI CH) Factors of the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996) and aggression dimensions (premeditated and impulsive aggression) in a sample of substance users receiving inpatient treatment. At the univariate level, PPI FD traits were significantly and positively related to premeditated aggression, but were not significantly related to impulsive aggression. PPI SCI traits were positively related to both forms of aggression, whereas PPI CH was not significantly related to either aggression dimension. Emotion regulation difficulties, as measured by the Difficulties with Emotion Regulation Scale (DERS; Gratz & Roemer, 2004), were negatively related to PPI FD traits, positively related to PPI SCI traits, and negatively related to PPI CH traits. Both PPI SCI and PPI FD traits exerted significant indirect effects on impulsive aggression through the DERS. In contrast, the DERS did not mediate the relations between psychopathic traits and premeditated aggression. Results provide a more nuanced understanding of the psychopathy-aggression relations and suggest that difficulties with emotion regulation may be an important mediator of the relations between psychopathy factors and impulsive aggression. PMID:25198433

A Combined Molecular Dynamics and Experimental Study of Doped Polypyrrole.

PubMed

Fonner, John M; Schmidt, Christine E; Ren, Pengyu

2010-10-01

Polypyrrole (PPy) is a biocompatible, electrically conductive polymer that has great potential for battery, sensor, and neural implant applications. Its amorphous structure and insolubility, however, limit the experimental techniques available to study its structure and properties at the atomic level. Previous theoretical studies of PPy in bulk are also scarce. Using ab initio calculations, we have constructed a molecular mechanics force field of chloride-doped PPy (PPyCl) and undoped PPy. This model has been designed to integrate into the OPLS force field, and parameters are available for the Gromacs and TINKER software packages. Molecular dynamics (MD) simulations of bulk PPy and PPyCl have been performed using this force field, and the effects of chain packing and electrostatic scaling on the bulk polymer density have been investigated. The density of flotation of PPyCl films has been measured experimentally. Amorphous X-ray diffraction of PPyCl was obtained and correlated with atomic structures sampled from MD simulations. The force field reported here is foundational for bridging the gap between experimental measurements and theoretical calculations for PPy based materials.

Chemical polymerization and characterization of surfactant directed of polypyrrole-tannin-CTAB nanocomposites

NASA Astrophysics Data System (ADS)

Abdi, Mahnaz M.; Azli, Nur Farhana Waheeda Mohd; Lim, Hong Ngee; Tahir, Paridah Md; Razalli, Rawaida Liyana; Hoong, Yeoh Beng

2017-12-01

In this research, Tannin (TA) from Acacia mangium tree was used to modify polypyrrole (PPy) composite with enhanced physical and structural properties. Composite nanostructure preparation was done in the presence of cationic surfactant, cetyltrimethylammonium bromide (CTAB) to improve surface area and electron transferring of resulting polymer. The Fourier Transform InfraRed (FT-IR) spectrum showed the characteristics peaks of functional group of PPy, TA, and CTAB in the resulting composite indicating the incorporation of TA and CTAB into PPy structure. The spherical structure was observed for PPy/TA prepared in the presence of CTAB with higher porosity compared with the PPy/TA. Cyclic voltammograms of modified SPE electrode using Ppy/TA/CTAB showed enhanced current response compared with the electrode modified by only PPy or PPy/TA.

Patient and public involvement in the early stages of clinical trial development: a systematic cohort investigation

PubMed Central

Gamble, Carrol; Dudley, Louise; Allam, Alison; Bell, Philip; Goodare, Heather; Hanley, Bec; Preston, Jennifer; Walker, Alison; Williamson, Paula; Young, Bridget

2014-01-01

Background Randomised controlled trials (RCTs) are considered particularly likely to benefit from patient and public involvement (PPI). Decisions made by professional researchers at the outset may go on to have a significant impact on the potential for PPI contributions. Objective To increase knowledge of PPI within the early development of RCTs by systematically describing the reported level, nature and acceptability of proposed PPI to the funders. Methods Documentation from the outline application process for all RCTs that received funding from the Health Technology Assessment (HTA) Programme 2006–2010 was requested. For each application, data were extracted on trial characteristics, references to PPI in the development of the outline application and funding Board feedback, and plans for PPI in the full application and after the trial was funded. Results 110 applications were eligible with outline applications available for 90 (82%). The cohort covered a wide range of interventions and conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated PPI within the development of the outline application itself; 32 (35.6%) planned involvement in the full application and 43 (48%) once the trial was funded. Recruitment at diagnosis and surgical interventions were less likely to describe PPI. Blinded trials and trials in which participants may receive placebo only, more frequently described PPI activity. The HTA commissioning Board feedback rarely referred to PPI. Conclusions Incorporation of PPI within the development of the outline application or specification of plans for future involvement was low. Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research. Comments on PPI by reviewers should be directional rather than state that an increase is required. Challenges facing applicants in initiating PPI prior to funding need to be addressed. PMID:25056972

Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding.

PubMed

Hamai, Kosuke; Iwamoto, Hiroshi; Ohshimo, Shinichiro; Wakabayashi, Yu; Ihara, Daisuke; Fujitaka, Kazunori; Hamada, Hironobu; Ono, Koichi; Hattori, Noboru

2018-05-22

To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding. A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non-PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan-Meier approach and the log-rank test. A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non-PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2-year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non-PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups. The use of PPI in bedridden tube-fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non-significant lower incidence of gastrointestinal bleeding than the non-PPI group. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 The Authors Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes

PubMed Central

2013-01-01

Background MicroRNAs (miRNAs) are important post-transcriptional regulators that have been demonstrated to play an important role in human diseases. Elucidating the associations between miRNAs and diseases at the systematic level will deepen our understanding of the molecular mechanisms of diseases. However, miRNA-disease associations identified by previous computational methods are far from completeness and more effort is needed. Results We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. Our approach achieved satisfactory performance in identifying known cancer-related miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from 71.3% to 91.3%. By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms. Conclusions In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. Our findings provide a broad perspective on the relationships between miRNAs and diseases and could potentially aid future research efforts concerning miRNA involvement in disease pathogenesis. PMID:24103777

Analysis of nonformulary use of PPIs and excess drug cost in a Veterans Affairs population.

PubMed

Ajumobi, Adewale B; Vuong, Ronald; Ahaneku, Hycienth

2012-01-01

In the Veterans Affairs (VA) health care system, a formulary-based approach without beneficiary cost-share incentives is used to limit the pharmacy cost of proton pump inhibitors (PPIs). However, the effectiveness of this approach in reducing the cost of PPIs is unknown. To (a) compare cost differences between the formulary PPI (generic omeprazole) and nonformulary PPIs and (b) evaluate reasons for nonformulary PPI use in order to identify opportunities to increase formulary drug use and discourage unnecessary use of nonformulary PPIs. A list of patients with receipt of PPIs from July 1, 2008, through June 30, 2009, was obtained from the Loma Linda VA Healthcare System pharmacy. Subjects with receipt of at least 120 units (capsules or tablets) of any PPI in the study period were considered long-term users. Demographic information was collected. Pharmacy consult records were reviewed to identify reasons for nonformulary use and dosing regimen of the formulary PPI prior to the switch. Cost analysis was done based on the VA contract prices for the drugs at the time of the study. Of 58,605 unique patients seen in this VA health care system in the 12-month period from July 1, 2008, through June 30, 2009, 13,713 (23.4%) received a PPI, and of these, 10,483 (76.4%) received at least 120 PPI units and were defined as long-term users. Of the long-term users, 9,462 (90.3%) were on the formulary PPI generic omeprazole, and 1,021 were nonformulary PPI users. Use of nonformulary PPIs (esomeprazole, pantoprazole, lansoprazole, rabeprazole) accounted for 10.5% of the PPI units and 9.7% of the users but 57.3% of total PPI cost. This pattern resulted in $570,263 in excess spending (i.e., $570,263 would have been saved in the study period if the nonformulary PPI users had used the formulary drug). The most common reason for nonformulary long-term PPI use was persistent symptoms (n=901, 88.2%). Adverse reaction was cited by 111 (10.9%) of nonformulary PPI users, 33.3% (n=37) of whom reported diarrhea. Of those who switched to a nonformulary PPI due to persistent symptoms, 363 (40.3%) were on once-daily dosing prior to the switch; 379 (42.1%) were on twice-daily dosing; and 159 (17.6%) were transfers from other places in which prior dosing information was not available in the hospital pharmacy records. One-year PPI use prevalence was 23% in this VA population, and long-term use prevalence was 18%. Nonformulary PPI use accounted for 10.5% of the PPI units and 9.7% of the users but 57.3% of total PPI drug cost. Opportunities to reduce nonformulary PPI use in order to reduce overall expenditures on PPIs include verification of optimal formulary PPI use, titration to twice-daily dosing, and confirmation of adverse reaction as being attributable to PPI use.

A novel method based on new adaptive LVQ neural network for predicting protein-protein interactions from protein sequences.

PubMed

Yousef, Abdulaziz; Moghadam Charkari, Nasrollah

2013-11-07

Protein-Protein interaction (PPI) is one of the most important data in understanding the cellular processes. Many interesting methods have been proposed in order to predict PPIs. However, the methods which are based on the sequence of proteins as a prior knowledge are more universal. In this paper, a sequence-based, fast, and adaptive PPI prediction method is introduced to assign two proteins to an interaction class (yes, no). First, in order to improve the presentation of the sequences, twelve physicochemical properties of amino acid have been used by different representation methods to transform the sequence of protein pairs into different feature vectors. Then, for speeding up the learning process and reducing the effect of noise PPI data, principal component analysis (PCA) is carried out as a proper feature extraction algorithm. Finally, a new and adaptive Learning Vector Quantization (LVQ) predictor is designed to deal with different models of datasets that are classified into balanced and imbalanced datasets. The accuracy of 93.88%, 90.03%, and 89.72% has been found on S. cerevisiae, H. pylori, and independent datasets, respectively. The results of various experiments indicate the efficiency and validity of the method. © 2013 Published by Elsevier Ltd.

Assessment of regional air quality by a concentration-dependent Pollution Permeation Index

PubMed Central

Liang, Chun-Sheng; Liu, Huan; He, Ke-Bin; Ma, Yong-Liang

2016-01-01

Although air quality monitoring networks have been greatly improved, interpreting their expanding data in both simple and efficient ways remains challenging. Therefore, needed are new analytical methods. We developed such a method based on the comparison of pollutant concentrations between target and circum areas (circum comparison for short), and tested its applications by assessing the air pollution in Jing-Jin-Ji, Yangtze River Delta, Pearl River Delta and Cheng-Yu, China during 2015. We found the circum comparison can instantly judge whether a city is a pollution permeation donor or a pollution permeation receptor by a Pollution Permeation Index (PPI). Furthermore, a PPI-related estimated concentration (original concentration plus halved average concentration difference) can be used to identify some overestimations and underestimations. Besides, it can help explain pollution process (e.g., Beijing’s PM2.5 maybe largely promoted by non-local SO2) though not aiming at it. Moreover, it is applicable to any region, easy-to-handle, and able to boost more new analytical methods. These advantages, despite its disadvantages in considering the whole process jointly influenced by complex physical and chemical factors, demonstrate that the PPI based circum comparison can be efficiently used in assessing air pollution by yielding instructive results, without the absolute need for complex operations. PMID:27731344

Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010).

PubMed

Gawron, Andrew J; Feinglass, Joseph; Pandolfino, John E; Tan, Bruce K; Bove, Michiel J; Shintani-Smith, Stephanie

2015-01-01

Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25-44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits, patient visits at academic medical centers (IRR 4.2, 95% CI 2.2-8.0), physician-owned practices (IRR 3.9, 95% CI 2.1-7.1), and community health centers (IRR 3.6, 95% CI 1.9-6.6) were all more likely to have brand name PPIs. Conclusion. PPI prescriptions with brand name only formulations are most strongly associated with physician practice type.

Elucidating the Construct Validity of the Psychopathic Personality Inventory Triarchic Scales.

PubMed

Sellbom, Martin; Wygant, Dustin B; Drislane, Laura E

2015-01-01

This study sought to replicate and extend Hall and colleagues' (2014) work on developing and validating scales from the Psychopathic Personality Inventory (PPI) to index the triarchic psychopathy constructs of boldness, meanness, and disinhibition. This study also extended Hall et al.'s initial findings by including the PPI Revised (PPI-R). A community sample (n = 240) weighted toward subclinical psychopathy traits and a male prison sample (n = 160) were used for this study. Results indicated that PPI-Boldness, PPI-Meanness, and PPI-Disinhibition converged with other psychopathy, personality, and behavioral criteria in ways conceptually expected from the perspective of the triarchic psychopathy model, including showing very strong convergent and discriminant validity with their Triarchic Psychopathy Measure counterparts. These findings further enhance the utility of the PPI and PPI-R in measuring these constructs.

Self-powered vision electronic-skin basing on piezo-photodetecting Ppy/PVDF pixel-patterned matrix for mimicking vision.

PubMed

Han, Wuxiao; Zhang, Linlin; He, Haoxuan; Liu, Hongmin; Xing, Lili; Xue, Xinyu

2018-06-22

The development of multifunctional electronic-skin that establishes human-machine interfaces, enhances perception abilities or has other distinct biomedical applications is the key to the realization of artificial intelligence. In this paper, a new self-powered (battery-free) flexible vision electronic-skin has been realized from pixel-patterned matrix of piezo-photodetecting PVDF/Ppy film. The electronic-skin under applied deformation can actively output piezoelectric voltage, and the outputting signal can be significantly influenced by UV illumination. The piezoelectric output can act as both the photodetecting signal and electricity power. The reliability is demonstrated over 200 light on-off cycles. The sensing unit matrix of 6 × 6 pixels on the electronic-skin can realize image recognition through mapping multi-point UV stimuli. This self-powered vision electronic-skin that simply mimics human retina may have potential application in vision substitution.

Self-powered vision electronic-skin basing on piezo-photodetecting Ppy/PVDF pixel-patterned matrix for mimicking vision

NASA Astrophysics Data System (ADS)

Han, Wuxiao; Zhang, Linlin; He, Haoxuan; Liu, Hongmin; Xing, Lili; Xue, Xinyu

2018-06-01

The development of multifunctional electronic-skin that establishes human-machine interfaces, enhances perception abilities or has other distinct biomedical applications is the key to the realization of artificial intelligence. In this paper, a new self-powered (battery-free) flexible vision electronic-skin has been realized from pixel-patterned matrix of piezo-photodetecting PVDF/Ppy film. The electronic-skin under applied deformation can actively output piezoelectric voltage, and the outputting signal can be significantly influenced by UV illumination. The piezoelectric output can act as both the photodetecting signal and electricity power. The reliability is demonstrated over 200 light on–off cycles. The sensing unit matrix of 6 × 6 pixels on the electronic-skin can realize image recognition through mapping multi-point UV stimuli. This self-powered vision electronic-skin that simply mimics human retina may have potential application in vision substitution.

Taking patient and public involvement online: qualitative evaluation of an online forum for palliative care and rehabilitation research.

PubMed

Brighton, Lisa Jane; Pask, Sophie; Benalia, Hamid; Bailey, Sylvia; Sumerfield, Marion; Witt, Jana; de Wolf-Linder, Susanne; Etkind, Simon Noah; Murtagh, Fliss E M; Koffman, Jonathan; Evans, Catherine J

2018-01-01

Patient and public involvement (PPI) is increasingly recognised as important in research. Most PPI takes place face-to-face, but this can be difficult for people who are unwell or have caring responsibilities. As these challenges are particularly common in palliative care and rehabilitation research, we developed an online forum for PPI: www.csipublicinvolvement.co.uk. In this study, we explored how well the online forum worked, if it is a suitable method for PPI, and how PPI members and researchers reacted to using it. We used an existing theory about online interventions to help choose the 'right' questions to ask participants. We invited PPI members and researchers who had used the online forum to participate in focus groups, and identified the most important themes discussed. Within this study, PPI members have helped with the interview questions, analysis, and write up. Overall, four PPI members and five researchers participated in the focus groups. Participants felt the online forum worked well and had multiple benefits. From the discussions, we identified four key questions to consider when developing online methods for PPI: how does the forum work, how does it engage people, how does it empower people, and what is the impact? Participants suggested the forum could be improved by being more PPI and less researcher focused. We conclude that when developing online methods of PPI, a functioning forum is not enough: it also needs to be engaging and empowering to have an impact. Future work can use these four domains when developing their own online PPI methods. Patient and public involvement (PPI) in research is increasingly recognised as important. Most PPI activities take place face-to-face, yet this can be difficult for people with ill health or caring responsibilities, and may exclude people from hard-to-reach populations (e.g. living in vulnerable social circumstances and/or remote geographical locations). These challenges are particularly pertinent in palliative care and rehabilitation research where people often live with, or care for someone with, advanced illness. In response to this, we aimed to test the functionality, feasibility, and acceptability of an online forum for PPI for palliative care and rehabilitation research (www.csipublicinvolvement.co.uk). We conducted separate focus groups with PPI members and researchers who had used the online forum. Data collection was underpinned by DeLone and Mclean's model of information systems success. Focus groups were recorded, transcribed, and analysed using inductive thematic analysis. Dual coding by two authors ensured rigour, and attention was paid to divergent cases. Four PPI members and five researchers participated in the focus groups (two PPI focus groups, one researcher focus group). The online forum was perceived as functional, feasible, and acceptable. Our analysis identified four key questions to consider when developing online methods for PPI: (1) how does the forum work, (2) how does it engage people, (3) how does it empower people, and (4) what is the impact? PPI members felt that the online forum was too researcher led, and needed to be more PPI focussed. When developing online methods of PPI, a functioning forum is not enough: it also needs to be engaging and empowering to have an impact. To optimise online involvement, future work should refer to these four domains and balance the needs of researchers and PPI members.

Potential Interference of Protein-Protein Interactions by Graphyne.

PubMed

Luan, Binquan; Huynh, Tien; Zhou, Ruhong

2016-03-10

Graphyne has attracted tremendous attention recently due to its many potentially superior properties relative to those of graphene. Although extensive efforts have been devoted to explore the applicability of graphyne as an alternative nanomaterial for state-of-the-art nanotechnology (including biomedical applications), knowledge regarding its possible adverse effects to biological cells is still lacking. Here, using large-scale all-atom molecular dynamics simulations, we investigate the potential toxicity of graphyne by interfering a protein-protein interaction (ppI). We found that graphyne could indeed disrupt the ppIs by cutting through the protein-protein interface and separating the protein complex into noncontacting ones, due to graphyne's dispersive and hydrophobic interaction with the hydrophobic residues residing at the dimer interface. Our results help to elucidate the mechanism of interaction between graphyne and ppI networks within a biological cell and provide insights for its hazard reduction.

Insight into the ionotropic gelation of chitosan using tripolyphosphate and pyrophosphate as cross-linkers.

PubMed

Sacco, Pasquale; Paoletti, Sergio; Cok, Michela; Asaro, Fioretta; Abrami, Michela; Grassi, Mario; Donati, Ivan

2016-11-01

Ionotropic gelation of chitosan by means of opposite charged ions represents an efficient alternative to covalent reticulation because of milder condition of use and, in general, higher biocompatibility of the resulting systems. In this work 90° light scattering (turbidimetry), circular dichroism (CD) and 1 H NMR measurements have been performed to study the interactions between the biopolymer and ionic cross-linkers tripolyphosphate (TPP) and pyrophosphate (PPi) in dilute solutions. Thereafter, a dialysis-based technique was exploited to fabricate tridimensional chitosan hydrogels based on both polyanions. Resulting matrices showed a different mechanical behavior because of their peculiar mesh-texture at micro/nano-scale: in the present contribution we demonstrate that TPP and PPi favor the formation of homogeneous and inhomogeneous systems, respectively. The different texture of networks could be exploited in future for the preparation of systems for the controlled release of molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing.

PubMed

Liu, Yao; Yang, Zhe; Du, Feng; Yang, Qiao; Hou, Jie; Yan, Xiaohong; Geng, Yi; Zhao, Yaning; Wang, Hua

2017-11-01

The present study aimed to explore the underlying molecular mechanisms of hepatocellular carcinoma (HCC). RNA‑sequencing profiles GSM629264 and GSM629265, from the GSE25599 data set, were downloaded from the Gene Expression Omnibus database and processed by quality evaluation. GSM629264 and GSM629265 were from HCC and adjacent non‑cancerous tissues, respectively. TopHat software was used for alignment analysis, followed by the detection of novel splicing sites. In addition, the Cufflinks software package was used to analyze gene expressions, and the Cuffdiff program was used to screen for differently expressed genes (DEGs) and differentially expressed splicing variants. Gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs were also performed. Transcription factors (TFs) and microRNAs (miRNAs) that regulate DEGs were identified, and a protein‑protein interaction (PPI) network was constructed. The hub node in the PPI network was obtained, and the TFs and miRNAs that regulated the hub node were further predicted. The quality of the sequencing data met the standards for analysis, and the clean reads were ~65%. Most sequencing reads mapped into coding sequence exons (CDS_exons), whereas other reads mapped into exon 3' untranslated regions (UTR_Exons), 5'UTR_Exons and Introns. Upregulated and downregulated DEGs between HCC and adjacent non‑cancerous tissues were screened. Genes of differentially expressed splicing variants were identified, including vesicle‑associated membrane protein 4, phosphatidylinositol glycan anchor biosynthesis class C, protein disulfide isomerase family A member 4 and growth arrest specific 5. Screened DEGs were enriched in the complement pathway. In the PPI network, ubiquitin C (UBC) was the hub node. UBC was predicted to be regulated by several TFs, including specificity protein 1 (SP1), FBJ murine osteosarcoma viral oncogene homolog (FOS), proto‑oncogene c‑JUN (JUN), FOS‑like antigen 2 (FOSL2) and SWI/SNF‑related, matrix‑associated, actin‑dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), and several miRNAs, including miR‑30 and miR‑181. Results from the present study demonstrated that UBC, SP1, FOS, JUN, FOSL2, SMARCA4, miR‑30 and miR‑181 may participate in the development of HCC.

Sensorimotor Gating in Neurotensin-1 Receptor Null Mice

PubMed Central

Feifel, D.; Pang, Z.; Shilling, P.D.; Melendez, G.; Schreiber, R.; Button, D.

2009-01-01

BACKGROUND Converging evidence has implicated endogenous neurotensin (NT) in the pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating and considered to be of strong relevance to neuropsychiatric disorders associated with psychosis and cognitive dysfunction. Mice genetically engineered to not express NT display deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 receptors have been most strongly implicated in mediating the psychosis relevant effects of NT such as attenuating PPI deficits. To investigate the role of NT1 receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and NT1 knockout (KO) mice. We also tested the effects of amphetamine and dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce PPI as well as the NT1 selective receptor agonist, PD149163, known to increase PPI in rats. METHODS Baseline PPI and acoustic startle response were measured in WT and NT1 knockout KO mice. After baseline testing, mice were tested again after receiving intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 mg/kg) on separate test days. RESULTS Baseline PPI and acoustic startle response in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice exhibited similar responses to the PPI-disrupting effects of dizocilpine and amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS The data does not support the regulation of baseline PPI or the PPI disruptive effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 receptor, although they support the antipsychotic potential of pharmacological activation of NT1 receptors by NT1 agonists. PMID:19596359

Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

PubMed

Gyawali, C Prakash

2017-09-01

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

Use of histamine H2 receptor antagonists and outcomes in patients with heart failure: a nationwide population-based cohort study.

PubMed

Adelborg, Kasper; Sundbøll, Jens; Schmidt, Morten; Bøtker, Hans Erik; Weiss, Noel S; Pedersen, Lars; Sørensen, Henrik Toft

2018-01-01

Histamine H 2 receptor activation promotes cardiac fibrosis and apoptosis in mice. However, the potential effectiveness of histamine H 2 receptor antagonists (H2RAs) in humans with heart failure is largely unknown. We examined the association between H2RA initiation and all-cause mortality among patients with heart failure. Using Danish medical registries, we conducted a nationwide population-based active-comparator cohort study of new users of H2RAs and proton pump inhibitors (PPIs) after first-time hospitalization for heart failure during the period 1995-2014. Hazard ratios (HRs) for all-cause mortality and hospitalization due to worsening of heart failure, adjusting for age, sex, and time between heart failure diagnosis and initiation of PPI or H2RA therapy, index year, comorbidity, cardiac surgery, comedications, and socioeconomic status were computed based on Cox regression analysis. Our analysis included 42,902 PPI initiators (median age 78 years, 46% female) and 3,296 H2RA initiators (median age 76 years, 48% female). Mortality risk was lower among H2RA initiators than PPI initiators after 1 year (26% vs 31%) and 5 years (60% vs 66%). In multivariable analyses, the 1-year HR was 0.80 (95% CI, 0.74-0.86) and the 5-year HR was 0.85 (95% CI, 0.80-0.89). These findings were consistent after propensity score matching and for ischemic and nonischemic heart failure, as for sex and age groups. The rate of hospitalization due to worsening of heart failure was lower among H2RA initiators than PPI initiators. In patients with heart failure, H2RA initiation was associated with 15%-20% lower mortality than PPI initiation.

Prediction of protein-protein interactions from amino acid sequences with ensemble extreme learning machines and principal component analysis.

PubMed

You, Zhu-Hong; Lei, Ying-Ke; Zhu, Lin; Xia, Junfeng; Wang, Bing

2013-01-01

Protein-protein interactions (PPIs) play crucial roles in the execution of various cellular processes and form the basis of biological mechanisms. Although large amount of PPIs data for different species has been generated by high-throughput experimental techniques, current PPI pairs obtained with experimental methods cover only a fraction of the complete PPI networks, and further, the experimental methods for identifying PPIs are both time-consuming and expensive. Hence, it is urgent and challenging to develop automated computational methods to efficiently and accurately predict PPIs. We present here a novel hierarchical PCA-EELM (principal component analysis-ensemble extreme learning machine) model to predict protein-protein interactions only using the information of protein sequences. In the proposed method, 11188 protein pairs retrieved from the DIP database were encoded into feature vectors by using four kinds of protein sequences information. Focusing on dimension reduction, an effective feature extraction method PCA was then employed to construct the most discriminative new feature set. Finally, multiple extreme learning machines were trained and then aggregated into a consensus classifier by majority voting. The ensembling of extreme learning machine removes the dependence of results on initial random weights and improves the prediction performance. When performed on the PPI data of Saccharomyces cerevisiae, the proposed method achieved 87.00% prediction accuracy with 86.15% sensitivity at the precision of 87.59%. Extensive experiments are performed to compare our method with state-of-the-art techniques Support Vector Machine (SVM). Experimental results demonstrate that proposed PCA-EELM outperforms the SVM method by 5-fold cross-validation. Besides, PCA-EELM performs faster than PCA-SVM based method. Consequently, the proposed approach can be considered as a new promising and powerful tools for predicting PPI with excellent performance and less time.

Patient and public involvement in the early stages of clinical trial development: a systematic cohort investigation.

PubMed

Gamble, Carrol; Dudley, Louise; Allam, Alison; Bell, Philip; Goodare, Heather; Hanley, Bec; Preston, Jennifer; Walker, Alison; Williamson, Paula; Young, Bridget

2014-07-23

Randomised controlled trials (RCTs) are considered particularly likely to benefit from patient and public involvement (PPI). Decisions made by professional researchers at the outset may go on to have a significant impact on the potential for PPI contributions. To increase knowledge of PPI within the early development of RCTs by systematically describing the reported level, nature and acceptability of proposed PPI to the funders. Documentation from the outline application process for all RCTs that received funding from the Health Technology Assessment (HTA) Programme 2006-2010 was requested. For each application, data were extracted on trial characteristics, references to PPI in the development of the outline application and funding Board feedback, and plans for PPI in the full application and after the trial was funded. 110 applications were eligible with outline applications available for 90 (82%). The cohort covered a wide range of interventions and conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated PPI within the development of the outline application itself; 32 (35.6%) planned involvement in the full application and 43 (48%) once the trial was funded. Recruitment at diagnosis and surgical interventions were less likely to describe PPI. Blinded trials and trials in which participants may receive placebo only, more frequently described PPI activity. The HTA commissioning Board feedback rarely referred to PPI. Incorporation of PPI within the development of the outline application or specification of plans for future involvement was low. Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research. Comments on PPI by reviewers should be directional rather than state that an increase is required. Challenges facing applicants in initiating PPI prior to funding need to be addressed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

MEGADOCK-Web: an integrated database of high-throughput structure-based protein-protein interaction predictions.

PubMed

Hayashi, Takanori; Matsuzaki, Yuri; Yanagisawa, Keisuke; Ohue, Masahito; Akiyama, Yutaka

2018-05-08

Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required. We have developed rapid PPI prediction software based on protein-protein docking, called MEGADOCK. In order to fully utilize the benefits of computational PPI predictions, it is necessary to construct a comprehensive database to gather prediction results and their predicted 3D complex structures and to make them easily accessible. Although several databases exist that provide predicted PPIs, the previous databases do not contain a sufficient number of entries for the purpose of discovering novel PPIs. In this study, we constructed an integrated database of MEGADOCK PPI predictions, named MEGADOCK-Web. MEGADOCK-Web provides more than 10 times the number of PPI predictions than previous databases and enables users to conduct PPI predictions that cannot be found in conventional PPI prediction databases. In MEGADOCK-Web, there are 7528 protein chains and 28,331,628 predicted PPIs from all possible combinations of those proteins. Each protein structure is annotated with PDB ID, chain ID, UniProt AC, related KEGG pathway IDs, and known PPI pairs. Additionally, MEGADOCK-Web provides four powerful functions: 1) searching precalculated PPI predictions, 2) providing annotations for each predicted protein pair with an experimentally known PPI, 3) visualizing candidates that may interact with the query protein on biochemical pathways, and 4) visualizing predicted complex structures through a 3D molecular viewer. MEGADOCK-Web provides a huge amount of comprehensive PPI predictions based on docking calculations with biochemical pathways and enables users to easily and quickly assess PPI feasibilities by archiving PPI predictions. MEGADOCK-Web also promotes the discovery of new PPIs and protein functions and is freely available for use at http://www.bi.cs.titech.ac.jp/megadock-web/ .

PPI layouts: BioJS components for the display of Protein-Protein Interactions

PubMed Central

Salazar, Gustavo A.; Meintjes, Ayton; Mulder, Nicola

2014-01-01

Summary: We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. Availability: http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753 PMID:25075288

Probing the Extent of Randomness in Protein Interaction Networks

DTIC Science & Technology

2008-07-11

other [54]. This characteristic is exemplified in Video S1, which contains a three-dimensional animation of the HT E . coli PPI network determined by...experiment using either yeast two-hybrid (Y2H) or tandem affinity purification (TAP) methodology: C. jejuni [18], E . coli (HT1) [12], E . coli (HT2...DCDWa C. jejuni [18] 1331 11664 0.095 0.095 2.91 2.85 E . coli (HT1) [12] 1289 5420 0.083 0.089 3.60 3.29 (HT2) [13] 3047 11477 0.064 0.085 3.37 3.27 C

A novel feature extraction scheme with ensemble coding for protein-protein interaction prediction.

PubMed

Du, Xiuquan; Cheng, Jiaxing; Zheng, Tingting; Duan, Zheng; Qian, Fulan

2014-07-18

Protein-protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of the development of high-throughput technologies and computational methods, many problems are still far from being solved. In this study, a novel predictor was designed by using the Random Forest (RF) algorithm with the ensemble coding (EC) method. To reduce computational time, a feature selection method (DX) was adopted to rank the features and search the optimal feature combination. The DXEC method integrates many features and physicochemical/biochemical properties to predict PPIs. On the Gold Yeast dataset, the DXEC method achieves 67.2% overall precision, 80.74% recall, and 70.67% accuracy. On the Silver Yeast dataset, the DXEC method achieves 76.93% precision, 77.98% recall, and 77.27% accuracy. On the human dataset, the prediction accuracy reaches 80% for the DXEC-RF method. We extended the experiment to a bigger and more realistic dataset that maintains 50% recall on the Yeast All dataset and 80% recall on the Human All dataset. These results show that the DXEC method is suitable for performing PPI prediction. The prediction service of the DXEC-RF classifier is available at http://ailab.ahu.edu.cn:8087/ DXECPPI/index.jsp.

Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

PubMed

Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

2016-11-20

Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

Cannabidiol Affects MK-801-Induced Changes in the PPI Learned Response of Capuchin Monkeys (Sapajus spp.).

PubMed

Saletti, Patricia G; Maior, Rafael S; Barros, Marilia; Nishijo, Hisao; Tomaz, Carlos

2017-01-01

There are several lines of evidence indicating a possible therapeutic action of cannabidiol (CBD) in schizophrenia treatment. Studies with rodents have demonstrated that CBD reverses MK-801 effects in prepulse inhibition (PPI) disruption, which may indicate that CBD acts by improving sensorimotor gating deficits. In the present study, we investigated the effects of CBD on a PPI learned response of capuchin monkeys ( Sapajus spp.). A total of seven monkeys were employed in this study. In Experiment 1, we evaluated the CBD (doses of 15, 30, 60 mg/kg, i.p.) effects on PPI. In Experiment 2, the effects of sub-chronic MK-801 (0.02 mg/kg, i.m.) on PPI were challenged by a CBD pre-treatment. No changes in PPI response were observed after CBD-alone administration. However, MK-801 increased the PPI response of our animals. CBD pre-treatment blocked the PPI increase induced by MK-801. Our findings suggest that CBD's reversal of the MK-801 effects on PPI is unlikely to stem from a direct involvement on sensorimotor mechanisms, but may possibly reflect its anxiolytic properties.

Centralities in simplicial complexes. Applications to protein interaction networks.

PubMed

Estrada, Ernesto; Ross, Grant J

2018-02-07

Complex networks can be used to represent complex systems which originate in the real world. Here we study a transformation of these complex networks into simplicial complexes, where cliques represent the simplices of the complex. We extend the concept of node centrality to that of simplicial centrality and study several mathematical properties of degree, closeness, betweenness, eigenvector, Katz, and subgraph centrality for simplicial complexes. We study the degree distributions of these centralities at the different levels. We also compare and describe the differences between the centralities at the different levels. Using these centralities we study a method for detecting essential proteins in PPI networks of cells and explain the varying abilities of the centrality measures at the different levels in identifying these essential proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contractor Past Performance Information (PPI) in Source Selection: A Comparison Study of Public and Private Sector

DTIC Science & Technology

2005-03-17

private sector . However, along the way, Government and private sector industry have begun to disagree about how PPI is collected and how PPI is used. Industry prefers a passive system of collecting delivery and quality data during contract performance, while the Federal Government uses both a passive system (similar to industry) as well as an active system of pulling PPI during contract performance. Industry uses PPI to establish and maintain a preferred vendor list from which to solicit bids, quotes, or proposals, while government uses PPI to assess

Effects of the PPy layer thickness on Co-PPy composite films

NASA Astrophysics Data System (ADS)

Haciismailoglu, Murside

2015-11-01

Co-PPy composite films were electrodeposited on ITO substrate from two different solutions potentiostatically. Firstly, the PPy layers with the thicknesses changing from 20 to 5000 nm were produced on ITO. Then Co was electrodeposited on these PPy/ITO substrates with a charge density of 1000 mC cm-2. The electrochemical properties were investigated by the current density-time transients and the variation of the elapsed time for the Co deposition depending on the PPy layer thickness. X-ray photoelectron (XPS) spectra indicated the presence of both Co metal and its oxides on the surface. The weak reflections of the Co3O4, CoO and hcp Co were detected by the X-ray diffraction (XRD) technique. According to scanning electron microscopy (SEM) images, the thickness of the PPy layer strongly affects the Co nucleation. The composite films with the PPy layer thinner than 200 nm and thicker than 2000 nm have an isotropic magnetic behavior due to the symmetrical crystal field. The composite films with the PPy layer thicknesses between 200 and 2000 nm have an anisotropic magnetic behavior attributable to the deterioration of this symmetrical crystal field by the PPy bubbles on the surface. All films are hard magnetic material, since the coercivities are larger than 125 Oe.

Key genes and pathways in measles and their interaction with environmental chemicals.

PubMed

Zhang, Rongqiang; Jiang, Hualin; Li, Fengying; Su, Ning; Ding, Yi; Mao, Xiang; Ren, Dan; Wang, Jing

2018-06-01

The aim of the present study was to explore key genes that may have a role in the pathology of measles virus infection and to clarify the interaction networks between environmental factors and differentially expressed genes (DEGs). After screening the database of the Gene Expression Omnibus of the National Center for Biotechnology Information, the dataset GSE5808 was downloaded and analyzed. A global normalization method was performed to minimize data inconsistencies and heterogeneity. DEGs during different stages of measles virus infection were explored using R software (v3.4.0). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs were performed using Cytoscape 3.4.0 software. A protein-protein interaction (PPI) network of the DEGs was obtained from the STRING database v9.05. A total of 43 DEGs were obtained from four analyzed sample groups, including 10 highly expressed genes and 33 genes with decreased expression. The most enriched pathways based on KEGG analysis were fatty acid elongation, cytokine-cytokine receptor interaction and RNA degradation. The genes mentioned in the PPI network were mainly associated with protein binding and chemokine activity. A total of 219 chemicals were identified that may, jointly or on their own, interact with the 6 DEGs between the control group and patients with measles (at hospital entry), including benzo(a)pyrene (BaP) and tetrachlorodibenzodioxin (TCDD). In conclusion, the present study revealed that chemokines and environmental chemicals, e.g. BaP and TCDD, may affect the development of measles.

Electromagnetic interference attenuation and shielding effect of quaternary Epoxy-PPy/Fe3O4-ZnO nanocomposite as a broad band microwave-absorber

NASA Astrophysics Data System (ADS)

Olad, Ali; Shakoori, Sahar

2018-07-01

An increase in the electromagnetic wave pollution generated from wireless telecommunication devices has devoted to a great request for exploiting microwave absorbing materials for themselves. The combination of inherently conducting polymers such as polypyrrole (PPy) with metal oxides has led to design ideal microwave absorbing materials which benefit both advantage effects of ICPs and metal oxide nanoparticles. Herein, the quaternary nanocomposite of Epoxy-PPy/Fe3O4-ZnO was prepared and tested for the absorption of X-band microwaves. Simultaneous application of metal oxides and conducting polypyrrole in the epoxy matrix was evaluated in order to increase the absorption intensity and broadness of microwaves in X-band region. The morphology, microstructure, and phase structure of Fe3O4, ZnO, and PPy, as well as quaternary nanocomposite were characterized and studied using FTIR, XRD, FESEM and TEM techniques. The presence of nanoparticles in the quaternary nanocomposite was confirmed by EDS. The magnetization of iron oxide was studied by VSM. The synergetic effect of iron oxide and zinc oxide nanoparticles in different weight ratios (Fe3O4/ZnO) on the electromagnetic wave absorption was evaluated. The electromagnetic parameters have been evaluated by the vector network analyzer in the frequency range of 8.2-12.4 GHz which is named as X-band region and is adequate for radar applications. The electromagnetic wave absorbing outcomes indicated that Epoxy-PPy/Fe3O4-ZnO quaternary nanocomposite has wide absorption area and high attenuation, which is believed to be due to dielectric loss properties related to the polypyrrole, magnetic loss factor of Fe3O4, and synergetic effects of components. The maximum reflection loss reached to -32.53 dB at 9.96 GHz with a nanocomposite thickness of 2 mm which is dedicated to the Epoxy-PPy/Fe3O4-ZnO with iron oxide to zinc oxide ratio of 2:1. The absorption bandwidth with the reflection loss lower than -10 dB (90% attenuation) was up to 4.2 GHz that covering a frequency range of 8.2-12.4 GHz. Results showed that absorber having %15 (w/w) polypyrrole/epoxy resin in Epoxy-PPy/Fe3O4-ZnO nanocomposite with iron oxide to zinc oxide ratio of 2:1 displays the best reflection loss properties. The loss curves illustrated the values of dielectric loss tangent and magnetic loss tangent of prepared nanocomposites which are in the range of 0.25-0.7 and -0.08 to 0.09 respectively. Therefore, microwave absorption mechanism is probably attributed to dielectric loss.

[Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-inflammatory drugs].

PubMed

Pimanov, S I; Makarenko, E V; Dikareva, E A

2015-01-01

To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.

Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced radiation pneumonitis.

PubMed

Su, QiaoLi; Wang, Duoning; Yuan, Bo; Liu, Feng; Lei, Yi; Li, Shuangqing

2014-11-01

The objective of this study was to explore the effects of proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy were retrospectively analyzed, and the patients were divided into PPI group and control group, according to whether or not PPIs were applied. The development and prognosis of patients and the effects of different doses of PPI on patient condition from two groups were compared. There were 57 PPI cases in PPI group and 27 cases in control group. Basic characteristics of patients were not statistically different between the two groups; however, white blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05), indicating that radiation pneumonitis tended to be more severe in PPI group. As regards effects of PPI on prognosis of two groups, remission rate of radiation pneumonia in PPI group was significantly less than that of the control group. Among 57 cases in PPI group, there were 31 patients applied with PPI ≤ 1DDD and 31 patients applied with PPI > 1DDD. In comparison of the various parameters of patients, 7 days after being applied with different doses of PPI, there were no significant differences between the parameters of radiation pneumonitis. PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.

Prediction and redesign of protein–protein interactions

PubMed Central

Lua, Rhonald C.; Marciano, David C.; Katsonis, Panagiotis; Adikesavan, Anbu K.; Wilkins, Angela D.; Lichtarge, Olivier

2014-01-01

Understanding the molecular basis of protein function remains a central goal of biology, with the hope to elucidate the role of human genes in health and in disease, and to rationally design therapies through targeted molecular perturbations. We review here some of the computational techniques and resources available for characterizing a critical aspect of protein function – those mediated by protein–protein interactions (PPI). We describe several applications and recent successes of the Evolutionary Trace (ET) in identifying molecular events and shapes that underlie protein function and specificity in both eukaryotes and prokaryotes. ET is a part of analytical approaches based on the successes and failures of evolution that enable the rational control of PPI. PMID:24878423

Study on Electro-polymerization Nano-micro Wiring System Imitating Axonal Growth of Artificial Neurons towards Machine Learning

NASA Astrophysics Data System (ADS)

Dang, Nguyen Tuan; Akai-Kasada, Megumi; Asai, Tetsuya; Saito, Akira; Kuwahara, Yuji; Hokkaido University Collaboration

2015-03-01

Machine learning using the artificial neuron network research is supposed to be the best way to understand how the human brain trains itself to process information. In this study, we have successfully developed the programs using supervised machine learning algorithm. However, these supervised learning processes for the neuron network required the very strong computing configuration. Derivation from the necessity of increasing in computing ability and in reduction of power consumption, accelerator circuits become critical. To develop such accelerator circuits using supervised machine learning algorithm, conducting polymer micro/nanowires growing process was realized and applied as a synaptic weigh controller. In this work, high conductivity Polypyrrole (PPy) and Poly (3, 4 - ethylenedioxythiophene) PEDOT wires were potentiostatically grown crosslinking the designated electrodes, which were prefabricated by lithography, when appropriate square wave AC voltage and appropriate frequency were applied. Micro/nanowire growing process emulated the neurotransmitter release process of synapses inside a biological neuron and wire's resistance variation during the growing process was preferred to as the variation of synaptic weigh in machine learning algorithm. In a cooperation with Graduate School of Information Science and Technology, Hokkaido University.

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS.

PubMed

Swerdlow, Neal R; Light, Gregory A; Sprock, Joyce; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Ray, Amrita; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2014-02-01

Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site "COGS-2" study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis×test site interaction. HCS>schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia "endophenotype" of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. Copyright © 2013 Elsevier B.V. All rights reserved.

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

PubMed Central

Swerdlow, Neal R.; Light, Gregory A.; Sprock, Joyce; Calkins, Monica E.; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Radant, Allen D.; Ray, Amrita; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Background Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site “COGS-2” study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Methods Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. Results 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis × test site interaction. HCS > schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. Discussion The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia “endophenotype” of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. PMID:24405980

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

NASA Astrophysics Data System (ADS)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

2011-02-01

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy: a study using impedance-pH monitoring.

PubMed

Frazzoni, Marzio; Conigliaro, Rita; Melotti, Gianluigi

2011-04-01

Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures.

Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.

PubMed

Bajaj, Jasmohan S; Acharya, Chathur; Fagan, Andrew; White, Melanie B; Gavis, Edith; Heuman, Douglas M; Hylemon, Phillip B; Fuchs, Michael; Puri, Puneet; Schubert, Mitchell L; Sanyal, Arun J; Sterling, Richard K; Stravitz, R Todd; Siddiqui, Mohammad S; Luketic, Velimir; Lee, Hannah; Sikaroodi, Masoumeh; Gillevet, Patrick M

2018-06-06

Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline. PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Risk of Community-Acquired Pneumonia with Outpatient Proton-Pump Inhibitor Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Lambert, Allison A.; Lam, Jennifer O.; Paik, Julie J.; Ugarte-Gil, Cesar; Drummond, M. Bradley; Crowell, Trevor A.

2015-01-01

Background Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults. Methods We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy. Results Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31). Discussion Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain. PMID:26042842

Cost Effectiveness of Gastroprotection with Proton Pump Inhibitors in Older Low-Dose Acetylsalicylic Acid Users in the Netherlands.

PubMed

Chau, Sek Hung; Sluiter, Reinier L; Kievit, Wietske; Wensing, Michel; Teichert, Martina; Hugtenburg, Jacqueline G

2017-05-01

The present study aimed to assess the cost effectiveness of concomitant proton pump inhibitor (PPI) treatment in low-dose acetylsalicylic acid (LDASA) users at risk of upper gastrointestinal (UGI) adverse effects as compared with no PPI co-medication with attention to the age-dependent influence of PPI-induced adverse effects. We used a Markov model to compare the strategy of PPI co-medication with no PPI co-medication in older LDASA users at risk of UGI adverse effects. As PPIs reduce the risk of UGI bleeding and dyspepsia, these risk factors were modelled together with PPI adverse effects for LDASA users 60-69, 70-79 (base case) and 80 years and older. Incremental cost-utility ratios (ICURs) were calculated as cost per quality-adjusted life-year (QALY) gained per age category. Furthermore, a budget impact analysis assessed the expected changes in expenditure of the Dutch healthcare system following the adoption of PPI co-treatment in all LDASA users potentially at risk of UGI adverse effects. PPI co-treatment of 70- to 79-year-old LDASA users, as compared with no PPI, resulted in incremental costs of €100.51 at incremental effects of 0.007 QALYs with an ICUR of €14,671/QALY. ICURs for 60- to 69-year-old LDASA users were €13,264/QALY and €64,121/QALY for patients 80 years and older. Initiation of PPI co-treatment for all Dutch LDASA users of 60 years and older at risk of UGI adverse effects but not prescribed a PPI (19%) would have cost €1,280,478 in the first year (year 2013 values). PPI co-medication in LDASA users at risk of UGI adverse effects is generally cost effective. However, this strategy becomes less cost effective with higher age, particularly in patients aged 80 years and older, mainly due to the increased risks of PPI-induced adverse effects.

Frequency of reporting on patient and public involvement (PPI) in research studies published in a general medical journal: a descriptive study.

PubMed

Price, Amy; Schroter, Sara; Snow, Rosamund; Hicks, Melissa; Harmston, Rebecca; Staniszewska, Sophie; Parker, Sam; Richards, Tessa

2018-03-23

While documented plans for patient and public involvement (PPI) in research are required in many grant applications, little is known about how frequently PPI occurs in practice. Low levels of reported PPI may mask actual activity due to limited PPI reporting requirements. This research analysed the frequency and types of reported PPI in the presence and absence of a journal requirement to include this information. A before and after comparison of PPI reported in research papers published in The BMJ before and 1 year after the introduction of a journal policy requiring authors to report if and how they involved patients and the public within their papers. Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1 (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the introduction of the policy, The BMJ published 152 research papers of which 16 (11%) reported PPI activity. Patients contributed to grant applications in addition to designing studies through to coauthorship and participation in study dissemination. Patient contributors were often not fully acknowledged; 6 of 17 (35%) papers acknowledged their contributions and 2 (12%) included them as coauthors. Infrequent reporting of PPI activity does not appear to be purely due to a failure of documentation. Reporting of PPI activity increased after the introduction of The BMJ 's policy, but activity both before and after was low and reporting was inconsistent in quality. Journals, funders and research institutions should collaborate to move us from the current situation where PPI is an optional extra to one where PPI is fully embedded in practice throughout the research process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Fast Response Ammonia Sensor Based on Coaxial PPy-PAN Nanofiber Yarn.

PubMed

Liu, Penghong; Wu, Shaohua; Zhang, Yue; Zhang, Hongnan; Qin, Xiaohong

2016-06-23

Highly orientated polypyrrole (PPy)-coated polyacrylonitrile (PAN) (PPy-PAN) nanofiber yarn was prepared with an electrospinning technique and in-situ chemical polymerization. The morphology and chemical structure of PPy-PAN nanofiber yarn was characterized by scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR), which indicated that the PPy as the shell layer was homogeneously and uniformly polymerized on the surface of PAN nanofiber. The effects of different concentration of doping acid on the responses of PPy-PAN nanofiber yarn sensor were investigated. The electrical responses of the gas sensor based on the PPy-PAN nanofiber yarn to ammonia were investigated at room temperature. The nanoyarn sensor composed of uniaxially aligned PPy-PAN nanofibers with a one-dimensional structure exhibited a transient response, and the response time was less than 1 s. The excellent sensing properties mentioned above give rise to good potential application prospects in the field of ammonia sensor.

Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1

PubMed Central

de la Croix Ndong, Jean; Makowski, Alexander James; Uppuganti, Sasidhar; Vignaux, Guillaume; Ono, Koichiro; Perrien, Daniel S.; Joubert, Simon; Baglio, Serena R.; Granchi, Donatella; Stevenson, David A.; Rios, Jonathan J.; Nyman, Jeffry S.; Elefteriou, Florent

2014-01-01

Mineralization of the skeleton depends on the balance between levels of pyrophosphate (PPi), an inhibitor of hydroxyapatite formation, and phosphate generated from PPi breakdown by alkaline phosphatase (ALP). We report here that ablation of Nf1, encoding the RAS/GTPase–activating protein neurofibromin, in bone–forming cells leads to supraphysiologic PPi accumulation, caused by a chronic ERK–dependent increase in genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank. It also prevents BMP2–induced osteoprogenitor differentiation and, consequently, expression of ALP and PPi breakdown, further contributing to PPi accumulation. The short stature, impaired bone mineralization and strength in mice lacking Nf1 in osteochondroprogenitors or osteoblasts could be corrected by enzyme therapy aimed at reducing PPi concentration. These results establish neurofibromin as an essential regulator of bone mineralization, suggest that altered PPi homeostasis contributes to the skeletal dysplasiae associated with neurofibromatosis type-1 (NF1), and that some of the NF1 skeletal conditions might be preventable pharmacologically. PMID:24997609

Parvalbumin and GAD65 Interneuron Inhibition in the Ventral Hippocampus Induces Distinct Behavioral Deficits Relevant to Schizophrenia

PubMed Central

Nguyen, Robin; Morrissey, Mark D.; Mahadevan, Vivek; Cajanding, Janine D.; Woodin, Melanie A.; Yeomans, John S.; Takehara-Nishiuchi, Kaori

2014-01-01

Hyperactivity within the ventral hippocampus (vHPC) has been linked to both psychosis in humans and behavioral deficits in animal models of schizophrenia. A local decrease in GABA-mediated inhibition, particularly involving parvalbumin (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying this hyperactive state. However, direct evidence is lacking for a causal role of vHPC GABA neurons in behaviors associated with schizophrenia. Here, we probed the behavioral function of two different but overlapping populations of vHPC GABA neurons that express either PV or GAD65 by selectively inhibiting these neurons with the pharmacogenetic neuromodulator hM4D. We show that acute inhibition of vHPC GABA neurons in adult mice results in behavioral changes relevant to schizophrenia. Inhibiting either PV or GAD65 neurons produced distinct behavioral deficits. Inhibition of PV neurons, affecting ∼80% of the PV neuron population, robustly impaired prepulse inhibition of the acoustic startle reflex (PPI), startle reactivity, and spontaneous alternation, but did not affect locomotor activity. In contrast, inhibiting a heterogeneous population of GAD65 neurons, affecting ∼40% of PV neurons and 65% of cholecystokinin neurons, increased spontaneous and amphetamine-induced locomotor activity and reduced spontaneous alternation, but did not alter PPI. Inhibition of PV or GAD65 neurons also produced distinct changes in network oscillatory activity in the vHPC in vivo. Together, these findings establish a causal role for vHPC GABA neurons in controlling behaviors relevant to schizophrenia and suggest a functional dissociation between the GABAergic mechanisms involved in hippocampal modulation of sensorimotor processes. PMID:25378161

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication.

PubMed

Agro, K; Blackhouse, G; Goeree, R; Willan, A R; Huang, J Q; Hunt, R H; O'Brien, B J

2001-01-01

To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.

A PYY Q62P variant linked to human obesity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy

2005-06-27

Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysismore » of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.« less

Development, fabrication, and modeling of highly sensitive conjugated polymer based piezoresistive sensors in electronic skin applications

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Naguib, Hani E.; Kwon, Roy H.

2016-04-01

Human intervention can be replaced through development of tools resulted from utilizing sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. Furthermore, a semi-analytical constriction resistance model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and the sensitivity of the sensor is obtained. The experimental results showed the good tracking ability of the proposed model.

The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

PubMed Central

Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

2015-01-01

Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

Counselors' Perspectives of Positive Psychology for the Treatment of Addiction: A Mixed Methods Pilot Study.

PubMed

Krentzman, Amy R; Barker, Stacey L

2016-01-01

Little is known about the use of positive psychology interventions (PPI) in addictions treatment. Questionnaires and interviews with alcohol and substance use disorder counselors explored theories of how PPIs might work, the degree to which they are used, and downsides. Results suggested that positive and pathology-based themes were attended in equal proportion, that substance abuse treatment should help clients develop a good life in recovery; that counselors already use PPI; and that PPI might counter negative cognitions and affect. Reservations for using PPI included relying on PPI exclusively and employing PPI indiscriminately without regard to client characteristics.

Counselors’ Perspectives of Positive Psychology for the Treatment of Addiction: A Mixed Methods Pilot Study

PubMed Central

Krentzman, Amy R.; Barker, Stacey L.

2016-01-01

Little is known about the use of positive psychology interventions (PPI) in addictions treatment. Questionnaires and interviews with alcohol and substance use disorder counselors explored theories of how PPIs might work, the degree to which they are used, and downsides. Results suggested that positive and pathology-based themes were attended in equal proportion, that substance abuse treatment should help clients develop a good life in recovery; that counselors already use PPI; and that PPI might counter negative cognitions and affect. Reservations for using PPI included relying on PPI exclusively and employing PPI indiscriminately without regard to client characteristics. PMID:27980355

Characterization of recombinant PPi-dependent 6-phosphofructokinases from Methylosinus trichosporium OB3b and Methylobacterium nodulans ORS 2060.

PubMed

Rozova, O N; Khmelenina, V N; Trotsenko, Y A

2012-03-01

The properties of the purified recombinant PPi-dependent 6-phosphofructokinases (PPi-PFKs) from the methanotroph Methylosinus trichosporium OB3b and rhizospheric phytosymbiont Methylobacterium nodulans ORS 2060 were determined. The dependence of activities of PPi-PFK-His(6)-tag from Ms. trichosporium OB3b (6 × 45 kDa) and PPi-PFK from Mb. nodulans ORS 2060 (4 × 43 kDa) on the concentrations of substrates of forward and reverse reactions conformed to Michaelis-Menten kinetics. Besides fructose-6-phosphate, the enzymes also phosphorylated sedoheptulose-7-phosphate. ADP or AMP (1 mM each) inhibited activity of the Ms. trichosporium PPi-PFK but did not affect the activity of the Mb. nodulans enzyme. Preference of PPi-PFKs to fructose-1,6-bisphosphate implied a predominant function of the enzymes in hexose phosphate synthesis in these bacteria. PPi-PFKs from the methylotrophs have low similarity of translated amino acid sequences (17% identity) and belong to different phylogenetic subgroups of type II 6-phosphofructokinases. The relationship of PPi-PFKs with microaerophilic character of Ms. trichosporium OB3b and adaptation of Mb. nodulans ORS 2060 to anaerobic phase of phytosymbiosis are discussed.

Proton Pump Inhibitors and Risk of Rhabdomyolysis.

PubMed

Duncan, Scott J; Howden, Colin W

2017-01-01

Proton pump inhibitors (PPIs) have been associated with a variety of adverse events, although the level of evidence for many of these is weak at best. Recently, one national regulatory authority has mandated a change to the labeling of one PPI based on reports of possible associated rhabdomyolysis. Thus, in this review we summarize the available evidence linking PPI use with rhabdomyolysis. The level of evidence is insufficient to establish a causal relationship and is largely based on sporadic case reports. In general, patients with suspected PPI-associated rhabdomyolysis have not been re-challenged with a PPI after recovery. The mechanism whereby PPIs might have been associated with rhabdomyolysis is unclear but possibly related to interaction with concomitantly administered drugs such as HMG-CoA reductase inhibitors (statins). For patients with rhabdomyolysis, a careful search must be made for possible etiological factors. In patients who recover from an episode of possible PPI-related rhabdomyolysis but do not have a genuine requirement for PPI treatment, the PPI should not be re-introduced. For those with a definite indication for ongoing PPI treatment, the PPI can be re-introduced but should preferably not be administered with a statin.

Facile synthesis of a silver nanoparticles/polypyrrole nanocomposite for non-enzymatic glucose determination.

PubMed

Poletti Papi, Maurício A; Caetano, Fabio R; Bergamini, Márcio F; Marcolino-Junior, Luiz H

2017-06-01

The present work describes the synthesis of a new conductive nanocomposite based on polypyrrole (PPy) and silver nanoparticles (PPy-AgNP) based on a facile reverse microemulsion method and its application as a non-enzymatic electrochemical sensor for glucose detection. Focusing on the best sensor performance, all experimental parameters used in the synthesis of nanocomposite were optimized based on its electrochemical response for glucose. Characterization of the optimized material by FT-IR, cyclic voltammetry, and DRX measurements and TEM images showed good monodispersion of semispherical Ag nanoparticles capped by PPy structure, with size average of 12±5nm. Under the best analytical conditions, the proposed sensor exhibited glucose response in linear dynamic range of 25 to 2500μmolL -1 , with limit of detection of 3.6μmolL -1 . Recovery studies with human saliva samples varying from 99 to 105% revealed the accuracy and feasibility of a non-enzymatic electrochemical sensor for glucose determination by easy construction and low-cost. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of Protein Abundance on High-Throughput Protein-Protein Interaction Detection

DTIC Science & Technology

2009-06-05

the interaction data sets we determined, via comparisons with strict randomized simulations , the propensity for essential proteins to selectively...and analysis of high- quality PPI data sets. Materials and Methods We analyzed protein interaction networks for yeast and E. coli determined from Y2H...we reinvestigated the centrality-lethality rule, which implies that proteins having more interactions are more likely to be essential. From analysis

A computational interactome for prioritizing genes associated with complex agronomic traits in rice (Oryza sativa).

PubMed

Liu, Shiwei; Liu, Yihui; Zhao, Jiawei; Cai, Shitao; Qian, Hongmei; Zuo, Kaijing; Zhao, Lingxia; Zhang, Lida

2017-04-01

Rice (Oryza sativa) is one of the most important staple foods for more than half of the global population. Many rice traits are quantitative, complex and controlled by multiple interacting genes. Thus, a full understanding of genetic relationships will be critical to systematically identify genes controlling agronomic traits. We developed a genome-wide rice protein-protein interaction network (RicePPINet, http://netbio.sjtu.edu.cn/riceppinet) using machine learning with structural relationship and functional information. RicePPINet contained 708 819 predicted interactions for 16 895 non-transposable element related proteins. The power of the network for discovering novel protein interactions was demonstrated through comparison with other publicly available protein-protein interaction (PPI) prediction methods, and by experimentally determined PPI data sets. Furthermore, global analysis of domain-mediated interactions revealed RicePPINet accurately reflects PPIs at the domain level. Our studies showed the efficiency of the RicePPINet-based method in prioritizing candidate genes involved in complex agronomic traits, such as disease resistance and drought tolerance, was approximately 2-11 times better than random prediction. RicePPINet provides an expanded landscape of computational interactome for the genetic dissection of agronomically important traits in rice. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

APID interactomes: providing proteome-based interactomes with controlled quality for multiple species and derived networks

PubMed Central

Alonso-López, Diego; Gutiérrez, Miguel A.; Lopes, Katia P.; Prieto, Carlos; Santamaría, Rodrigo; De Las Rivas, Javier

2016-01-01

APID (Agile Protein Interactomes DataServer) is an interactive web server that provides unified generation and delivery of protein interactomes mapped to their respective proteomes. This resource is a new, fully redesigned server that includes a comprehensive collection of protein interactomes for more than 400 organisms (25 of which include more than 500 interactions) produced by the integration of only experimentally validated protein–protein physical interactions. For each protein–protein interaction (PPI) the server includes currently reported information about its experimental validation to allow selection and filtering at different quality levels. As a whole, it provides easy access to the interactomes from specific species and includes a global uniform compendium of 90,379 distinct proteins and 678,441 singular interactions. APID integrates and unifies PPIs from major primary databases of molecular interactions, from other specific repositories and also from experimentally resolved 3D structures of protein complexes where more than two proteins were identified. For this purpose, a collection of 8,388 structures were analyzed to identify specific PPIs. APID also includes a new graph tool (based on Cytoscape.js) for visualization and interactive analyses of PPI networks. The server does not require registration and it is freely available for use at http://apid.dep.usal.es. PMID:27131791

Three-dimensional graphene-polypyrrole hybrid electrochemical actuator

NASA Astrophysics Data System (ADS)

Liu, Jia; Wang, Zhi; Zhao, Yang; Cheng, Huhu; Hu, Chuangang; Jiang, Lan; Qu, Liangti

2012-11-01

The advancement of mechanical actuators benefits from the development of new structural materials with prominent properties. A novel three-dimensional (3D) hydrothermally converted graphene and polypyrrole (G-PPy) hybrid electrochemical actuator is presented, which is prepared via a convenient hydrothermal process, followed by in situ electropolymerization of pyrrole. The 3D pore-interconnected G-PPy pillar exhibits strong actuation responses superior to pure graphene and PPy film. In response to the low potentials of +/-0.8 V, the saturated strain of 3D G-PPy pillar can reach a record of 2.5%, which is more than 10 times higher than that of carbon nanotube film and about 3 times that of unitary graphene film under an applied potential of +/-1.2 V. Also, the 3D G-PPy actuator exhibits high actuation durability with high operating load as demonstrated by an 11 day continuous measurement. Finally, a proof-of-concept application of 3D G-PPy as smart filler for on/off switch is also demonstrated, which indicates the great potential of the 3D G-PPy structure developed in this study for advanced actuator systems.The advancement of mechanical actuators benefits from the development of new structural materials with prominent properties. A novel three-dimensional (3D) hydrothermally converted graphene and polypyrrole (G-PPy) hybrid electrochemical actuator is presented, which is prepared via a convenient hydrothermal process, followed by in situ electropolymerization of pyrrole. The 3D pore-interconnected G-PPy pillar exhibits strong actuation responses superior to pure graphene and PPy film. In response to the low potentials of +/-0.8 V, the saturated strain of 3D G-PPy pillar can reach a record of 2.5%, which is more than 10 times higher than that of carbon nanotube film and about 3 times that of unitary graphene film under an applied potential of +/-1.2 V. Also, the 3D G-PPy actuator exhibits high actuation durability with high operating load as demonstrated by an 11 day continuous measurement. Finally, a proof-of-concept application of 3D G-PPy as smart filler for on/off switch is also demonstrated, which indicates the great potential of the 3D G-PPy structure developed in this study for advanced actuator systems. Electronic supplementary information (ESI) available: Experimental setup for fabrication of G-PPy hybrid structure, and movie showing the on/off response of G-PPy filler. See DOI: 10.1039/c2nr32699j

PPi-dependent phosphofructotransferase (phosphofructokinase) activity in the mollicutes (mycoplasma) Acholeplasma laidlawii.

PubMed Central

Pollack, J D; Williams, M V

1986-01-01

A PPi-dependent phosphofructotransferase (PPi-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.90) which catalyzes the conversion of fructose 6 phosphate (F-6-P) to fructose 1,6-bisphosphate (F-1, 6-P2) was isolated from a cytoplasmic fraction of Acholeplasma laidlawii B-PG9 and partially purified (430-fold). PPi was required as the phosphate donor. ATP, dATP, CTP, dCTP, GTP, dGTP, UTP, dUTP, ITP, TTP, ADP, or Pi could not substitute for PPi. The PPi-dependent reaction (2.0 mM PPi) was not altered in the presence of any of these nucleotides (2.0 mM) or in the presence of smaller (less than or equal to 300 microM) amounts of fructose 2,6-bisphosphate, (NH4)2SO4, AMP, citrate, GDP, or phosphoenolpyruvate. Mg2+ and a pH of 7.4 were required for maximum activity. The partially purified enzyme in sucrose density gradient experiments had an approximate molecular weight of 74,000 and a sedimentation coefficient of 6.7. A second form of the enzyme (molecular weight, 37,000) was detected, although in relatively smaller amounts, by using Blue Sepharose matrix when performing electrophoresis experiments. The back reaction, F-1, 6-P2 to F-6-P, required Pi; arsenate could substitute for Pi, but not PPi or any other nucleotide tested. The computer-derived kinetic constants (+/- standard deviation) for the reaction in the PPi-driven direction of F-1, 6-P2 were as follows: v, 38.9 +/- 0.48 mM min-1; Ka(PPi), 0.11 +/- 0.04 mM; Kb(F-6-P), 0.65 +/- 0.15 mM; and Kia(PPi), 0.39 +/- 0.11 mM. A. laidlawii B-PG9 required PPi not only for the PPi-phosphofructotransferase reaction which we describe but also for purine nucleoside kinase activity. a dependency unknown in any other organism. In A. laidlawii B-PG9, the PPi requirement may be met by reactions in this organism already known to synthesize PPi (e.g., dUTPase and purine nucleobase phosphoribosyltransferases). In almost all other cells, the conversion of F-6-P to F-1,6-P2 is ATP dependent, and the reaction is generally considered to be the rate-limiting step of glycolysis. The ability of A. laidlawii B-PG9 and one other acholeplasma to use PPi instead of ATP as an energy source may offer these cytochrome-deficient organisms some metabolic advantage and may represent a conserved metabolic remnant of an earlier evolutionary process. PMID:3001032

MPact: the MIPS protein interaction resource on yeast.

PubMed

Güldener, Ulrich; Münsterkötter, Martin; Oesterheld, Matthias; Pagel, Philipp; Ruepp, Andreas; Mewes, Hans-Werner; Stümpflen, Volker

2006-01-01

In recent years, the Munich Information Center for Protein Sequences (MIPS) yeast protein-protein interaction (PPI) dataset has been used in numerous analyses of protein networks and has been called a gold standard because of its quality and comprehensiveness [H. Yu, N. M. Luscombe, H. X. Lu, X. Zhu, Y. Xia, J. D. Han, N. Bertin, S. Chung, M. Vidal and M. Gerstein (2004) Genome Res., 14, 1107-1118]. MPact and the yeast protein localization catalog provide information related to the proximity of proteins in yeast. Beside the integration of high-throughput data, information about experimental evidence for PPIs in the literature was compiled by experts adding up to 4300 distinct PPIs connecting 1500 proteins in yeast. As the interaction data is a complementary part of CYGD, interactive mapping of data on other integrated data types such as the functional classification catalog [A. Ruepp, A. Zollner, D. Maier, K. Albermann, J. Hani, M. Mokrejs, I. Tetko, U. Güldener, G. Mannhaupt, M. Münsterkötter and H. W. Mewes (2004) Nucleic Acids Res., 32, 5539-5545] is possible. A survey of signaling proteins and comparison with pathway data from KEGG demonstrates that based on these manually annotated data only an extensive overview of the complexity of this functional network can be obtained in yeast. The implementation of a web-based PPI-analysis tool allows analysis and visualization of protein interaction networks and facilitates integration of our curated data with high-throughput datasets. The complete dataset as well as user-defined sub-networks can be retrieved easily in the standardized PSI-MI format. The resource can be accessed through http://mips.gsf.de/genre/proj/mpact.

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal-thalamus-hippocampus network.

PubMed

Thielen, Jan-Willem; Hong, Donghyun; Rohani Rankouhi, Seyedmorteza; Wiltfang, Jens; Fernández, Guillén; Norris, David G; Tendolkar, Indira

2018-06-01

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long-term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ-aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face-name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory-related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory-related functional connectivity in a medial prefrontal-thalamus-hippocampus network. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

A Pyrophosphate Based Energy Generating Module

DTIC Science & Technology

2008-12-01

OMB control number. 1. REPORT DATE DEC 2008 2 . REPORT TYPE N/A 3 . DATES COVERED - 4. TITLE AND SUBTITLE A Pyrophosphate Based Energy...for each substrate (PPi, PEP, and AMP) using double reciprocal Lineweaver-Burk plots of saturation data. 10| 2 10| 3 10|4 10|5 10|6 10|7 10-11 10- 10...Partitioning 1 2 3 4 Bilayer - + + + α-Hemolysin - - + + Upper Reservoir +PPi, +PEP +PPi, +PEP +PPi, +PEP +PPi, +PEP, +Luc Lower Reservoir +AMP

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.

PubMed

Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won

2018-01-15

The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

Association of Proton Pump Inhibitor (PPI) Use with Energy Intake, Physical Activity, and Weight Gain

PubMed Central

Czwornog, Jennifer L.; Austin, Gregory L.

2015-01-01

Studies suggest proton pump inhibitor (PPI) use impacts body weight regulation, though the effect of PPIs on energy intake, energy extraction, and energy expenditure is unknown. We used data on 3073 eligible adults from the National Health and Nutrition Examination Survey (NHANES). Medication use, energy intake, diet composition, and physical activity were extracted from NHANES. Multivariate regression models included confounding variables. Daily energy intake was similar between PPI users and non-users (p = 0.41). Diet composition was similar between the two groups, except that PPI users consumed a slightly greater proportion of calories from fat (34.5% vs. 33.2%; p = 0.02). PPI users rated themselves as being as physically active as their age/gender-matched peers and reported similar frequencies of walking or biking. However, PPI users were less likely to have participated in muscle-strengthening activities (OR: 0.53; 95% CI: 0.30–0.95). PPI users reported similar sedentary behaviors to non-users. Male PPI users had an increase in weight (of 1.52 ± 0.59 kg; p = 0.021) over the previous year compared to non-users, while female PPI users had a non-significant increase in weight. The potential mechanisms for PPI-associated weight gain are unclear as we did not find evidence for significant differences in energy intake or markers of energy expenditure. PMID:26492268

Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study.

PubMed

Kruszelnicka, Olga; Świerszcz, Jolanta; Bednarek, Jacek; Chyrchel, Bernadeta; Surdacki, Andrzej; Nessler, Jadwiga

2016-04-15

A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients' age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies.

Proton Pump Inhibitor Use and Magnesium Concentrations in Hemodialysis Patients: A Cross-Sectional Study

PubMed Central

Nakashima, Akio; Ohkido, Ichiro; Yokoyama, Keitaro; Mafune, Aki; Urashima, Mitsuyoshi; Yokoo, Takashi

2015-01-01

Magnesium concentration is a proven predictor of mortality in hemodialysis patients. Recent reports have indicated that proton pump inhibitor (PPI) use affects serum magnesium levels, however few studies have investigated the relationship between PPI use and magnesium levels in hemodialysis patients. This study aimed to clarify the association between PPI use and serum magnesium levels in hemodialysis patients. We designed this cross sectional study and included 1189 hemodialysis patients in stable condition. Associations between PPI and magnesium-related factors, as well as other possible confounders, were evaluated using a multiple regression model. We defined hypomagnesemia as a value < 2.0 mg/dL, and created comparable logistic regression models to assess the association between PPI use and hypomagnesemia. PPI use is associated with a significantly lower mean serum magnesium level than histamine 2 (H2) receptor antagonists or no acid-suppressive medications (mean [SD] PPI: 2.52 [0.45] mg/dL; H2 receptor antagonist: 2.68 [0.41] mg/dL; no acid suppressive medications: 2.68 [0.46] mg/dL; P = 0.001). Hypomagnesemia remained significantly associated with PPI (adjusted OR, OR: 2.05; 95% CI: 1.14–3.69; P = 0.017). PPI use is associated with an increased risk of hypomagnesemia in hemodialysis patients. Future prospective studies are needed to explore magnesium replacement in PPI users on hemodialysis. PMID:26618538

Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

PubMed Central

Engin, H. Billur; Guney, Emre; Keskin, Ozlem; Oliva, Baldo; Gursoy, Attila

2013-01-01

Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis. PMID:24278371

Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise

PubMed Central

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical “noise” that warrant further analysis for causal variants. PMID:25409314

Protein interaction networks reveal novel autism risk genes within GWAS statistical noise.

PubMed

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical "noise" that warrant further analysis for causal variants.

Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder.

PubMed

Vrana, Scott R; Calhoun, Patrick S; McClernon, F Joseph; Dennis, Michelle F; Lee, Sherman T; Beckham, Jean C

2013-12-01

Cigarette smokers smoke in part because nicotine helps regulate attention. Prepulse inhibition (PPI) of the startle reflex is a measure of early attentional gating that is reduced in abstinent smokers and in groups with attention regulation difficulties. Attention difficulties are found in people with posttraumatic stress disorder (PTSD). The aim of this study is to assess whether smoking and abstinence differentially affect the startle response and PPI in smokers with and without PTSD. Startle response and PPI (prepulses at 60, 120, or 240 ms) were measured in smokers with (N = 39) and without (N = 61) PTSD, while smoking and again while abstinent. Participants with PTSD produced both larger magnitude and faster latency startle responses than controls. Across groups, PPI was greater when smoking than when abstinent. The PTSD and control group exhibited different patterns of PPI across prepulse intervals when smoking and when abstinent. Older age was associated with reduced PPI, but only when abstinent from smoking. The effects of PTSD on startle magnitude and of smoking on PPI replicate earlier studies. The different pattern of PPI exhibited in PTSD and control groups across prepulse intervals, while smoking and abstinent suggests that previous research on smoking and PPI has been limited by not including longer prepulse intervals, and that nicotine may affect the time course as well as increasing the level of PPI. The reduced PPI among older participants during abstinence suggests that nicotine may play a role in maintaining attention in older smokers, which may motivate continued smoking in older individuals.

An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

PubMed

Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

2017-01-01

Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently, once outside the cell, they must refold into their active form. This step often requires the assistance of bacterial folding proteins, such as PPIases. In this work, we investigate the role of PPIases in S. aureus and uncover a cyclophilin-type enzyme that assists in the folding/refolding of staphylococcal nuclease. Copyright © 2016 American Society for Microbiology.

Exploring Wound-Healing Genomic Machinery with a Network-Based Approach

PubMed Central

Vitali, Francesca; Marini, Simone; Balli, Martina; Grosemans, Hanne; Sampaolesi, Maurilio; Lussier, Yves A.; Cusella De Angelis, Maria Gabriella; Bellazzi, Riccardo

2017-01-01

The molecular mechanisms underlying tissue regeneration and wound healing are still poorly understood despite their importance. In this paper we develop a bioinformatics approach, combining biology and network theory to drive experiments for better understanding the genetic underpinnings of wound healing mechanisms and for selecting potential drug targets. We start by selecting literature-relevant genes in murine wound healing, and inferring from them a Protein-Protein Interaction (PPI) network. Then, we analyze the network to rank wound healing-related genes according to their topological properties. Lastly, we perform a procedure for in-silico simulation of a treatment action in a biological pathway. The findings obtained by applying the developed pipeline, including gene expression analysis, confirms how a network-based bioinformatics method is able to prioritize candidate genes for in vitro analysis, thus speeding up the understanding of molecular mechanisms and supporting the discovery of potential drug targets. PMID:28635674

Predicting Functions of Proteins in Mouse Based on Weighted Protein-Protein Interaction Network and Protein Hybrid Properties

PubMed Central

Shi, Xiaohe; Lu, Wen-Cong; Cai, Yu-Dong; Chou, Kuo-Chen

2011-01-01

Background With the huge amount of uncharacterized protein sequences generated in the post-genomic age, it is highly desirable to develop effective computational methods for quickly and accurately predicting their functions. The information thus obtained would be very useful for both basic research and drug development in a timely manner. Methodology/Principal Findings Although many efforts have been made in this regard, most of them were based on either sequence similarity or protein-protein interaction (PPI) information. However, the former often fails to work if a query protein has no or very little sequence similarity to any function-known proteins, while the latter had similar problem if the relevant PPI information is not available. In view of this, a new approach is proposed by hybridizing the PPI information and the biochemical/physicochemical features of protein sequences. The overall first-order success rates by the new predictor for the functions of mouse proteins on training set and test set were 69.1% and 70.2%, respectively, and the success rate covered by the results of the top-4 order from a total of 24 orders was 65.2%. Conclusions/Significance The results indicate that the new approach is quite promising that may open a new avenue or direction for addressing the difficult and complicated problem. PMID:21283518

Network-based prediction and knowledge mining of disease genes.

PubMed

Carson, Matthew B; Lu, Hui

2015-01-01

In recent years, high-throughput protein interaction identification methods have generated a large amount of data. When combined with the results from other in vivo and in vitro experiments, a complex set of relationships between biological molecules emerges. The growing popularity of network analysis and data mining has allowed researchers to recognize indirect connections between these molecules. Due to the interdependent nature of network entities, evaluating proteins in this context can reveal relationships that may not otherwise be evident. We examined the human protein interaction network as it relates to human illness using the Disease Ontology. After calculating several topological metrics, we trained an alternating decision tree (ADTree) classifier to identify disease-associated proteins. Using a bootstrapping method, we created a tree to highlight conserved characteristics shared by many of these proteins. Subsequently, we reviewed a set of non-disease-associated proteins that were misclassified by the algorithm with high confidence and searched for evidence of a disease relationship. Our classifier was able to predict disease-related genes with 79% area under the receiver operating characteristic (ROC) curve (AUC), which indicates the tradeoff between sensitivity and specificity and is a good predictor of how a classifier will perform on future data sets. We found that a combination of several network characteristics including degree centrality, disease neighbor ratio, eccentricity, and neighborhood connectivity help to distinguish between disease- and non-disease-related proteins. Furthermore, the ADTree allowed us to understand which combinations of strongly predictive attributes contributed most to protein-disease classification. In our post-processing evaluation, we found several examples of potential novel disease-related proteins and corresponding literature evidence. In addition, we showed that first- and second-order neighbors in the PPI network could be used to identify likely disease associations. We analyzed the human protein interaction network and its relationship to disease and found that both the number of interactions with other proteins and the disease relationship of neighboring proteins helped to determine whether a protein had a relationship to disease. Our classifier predicted many proteins with no annotated disease association to be disease-related, which indicated that these proteins have network characteristics that are similar to disease-related proteins and may therefore have disease associations not previously identified. By performing a post-processing step after the prediction, we were able to identify evidence in literature supporting this possibility. This method could provide a useful filter for experimentalists searching for new candidate protein targets for drug repositioning and could also be extended to include other network and data types in order to refine these predictions.

Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier methods.

PubMed

Tuo, Youlin; An, Ning; Zhang, Ming

2018-03-01

The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed. The feature genes identified by topological characteristics were then used for support vector machine (SVM) classifier training and verification. The accuracy of the SVM classifier was then evaluated using another independent dataset from The Cancer Genome Atlas database. Finally, function and pathway enrichment analyses for genes in the SVM classifier were performed. A total of 541 feature genes were identified between metastatic and non‑metastatic samples. The top 10 genes with the highest betweenness centrality values in the PPI network of feature genes were Nuclear RNA Export Factor 1, cyclin‑dependent kinase 2 (CDK2), myelocytomatosis proto‑oncogene protein (MYC), Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat domain 1, proteasome 26S subunit non‑ATPase 2 and telomeric repeat binding factor 2. The cyclin‑dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1 (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top 30 feature genes was able to distinguish metastatic samples from non‑metastatic samples [correct rate, specificity, positive predictive value and negative predictive value >0.89; sensitivity >0.84; area under the receiver operating characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an independent dataset (35 metastatic samples and 143 non‑metastatic samples) revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated functions and pathways were the most significant terms of the 30 feature genes. A SVM classifier was constructed to assess the possibility of breast cancer metastasis, which presented high accuracy in several independent datasets. CDK2, CDKN1A, E2F1 and MYC were indicated as the potential feature genes in metastatic breast cancer.

Role of miR-452-5p in the tumorigenesis of prostate cancer: A study based on the Cancer Genome Atl(TCGA), Gene Expression Omnibus (GEO), and bioinformatics analysis.

PubMed

Gao, Li; Zhang, Li-Jie; Li, Sheng-Hua; Wei, Li-Li; Luo, Bin; He, Rong-Quan; Xia, Shuang

2018-03-06

MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), PANTHER pathway analyses, and a disease ontology (DG) analysis were performed to find the molecular functions of the target genes from GSE datasets and miRWalk. Finally, we validated hub genes from the protein-protein interaction (PPI) networks of the target genes in the Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA). Narrowing down the optimal target genes was conducted by seeking the common parts of up-regulated genes from GEPIA, down-regulated genes from GSE datasets, and predicted genes in miRWalk. Based on mining of GEO and ArrayExpress microarray chips and miRNA-Seq data in the TCGA database, which includes 1007 prostate cancer samples and 387 non-cancer samples, miR-452-5p is shown to be down-regulated in prostate cancer. GO, KEGG, and PANTHER pathway analyses suggested that the target genes might participate in important biological processes, such as transforming growth factor beta signaling and the positive regulation of brown fat cell differentiation and mesenchymal cell differentiation, as well as the Ras signaling pathway and pathways regulating the pluripotency of stem cells and arrhythmogenic right ventricular cardiomyopathy (ARVC). Nine genes-GABBR, PNISR, NTSR1, DOCK1, EREG, SFRP1, PTGS2, LEF1, and BMP2-were defined as hub genes in the PPI network. Three genes-FAM174B, SLC30A4, and SLIT1-were jointly shared by GEPIA, the GSE datasets, and miRWalk. Down-regulated miR-452-5p might play an essential role in the tumorigenesis of prostate cancer. Copyright © 2018. Published by Elsevier GmbH.

Double network bacterial cellulose hydrogel to build a biology-device interface.

PubMed

Shi, Zhijun; Li, Ying; Chen, Xiuli; Han, Hongwei; Yang, Guang

2014-01-21

Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.

Double network bacterial cellulose hydrogel to build a biology-device interface

NASA Astrophysics Data System (ADS)

Shi, Zhijun; Li, Ying; Chen, Xiuli; Han, Hongwei; Yang, Guang

2013-12-01

Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.

Protein-protein interaction networks (PPI) and complex diseases

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Rezaei-Tavirani, Mostafa; Goliaei, Bahram

2014-01-01

The physical interaction of proteins which lead to compiling them into large densely connected networks is a noticeable subject to investigation. Protein interaction networks are useful because of making basic scientific abstraction and improving biological and biomedical applications. Based on principle roles of proteins in biological function, their interactions determine molecular and cellular mechanisms, which control healthy and diseased states in organisms. Therefore, such networks facilitate the understanding of pathogenic (and physiologic) mechanisms that trigger the onset and progression of diseases. Consequently, this knowledge can be translated into effective diagnostic and therapeutic strategies. Furthermore, the results of several studies have proved that the structure and dynamics of protein networks are disturbed in complex diseases such as cancer and autoimmune disorders. Based on such relationship, a novel paradigm is suggested in order to confirm that the protein interaction networks can be the target of therapy for treatment of complex multi-genic diseases rather than individual molecules with disrespect the network. PMID:25436094

Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

PubMed Central

Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

2015-01-01

Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

Inflammatory Cytokines Induce a Unique Mineralizing Phenotype in Mesenchymal Stem Cells Derived from Human Bone Marrow*

PubMed Central

Ferreira, Elisabeth; Porter, Ryan M.; Wehling, Nathalie; O'Sullivan, Regina P.; Liu, Fangjun; Boskey, Adele; Estok, Daniel M.; Harris, Mitchell B.; Vrahas, Mark S.; Evans, Christopher H.; Wells, James W.

2013-01-01

Bone marrow contains mesenchymal stem cells (MSCs) that can differentiate along multiple mesenchymal lineages. In this capacity they are thought to be important in the intrinsic turnover and repair of connective tissues while also serving as a basis for tissue engineering and regenerative medicine. However, little is known of the biological responses of human MSCs to inflammatory conditions. When cultured with IL-1β, marrow-derived MSCs from 8 of 10 human subjects deposited copious hydroxyapatite, in which authenticity was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy revealed the production of fine needles of hydroxyapatite in conjunction with matrix vesicles. Alkaline phosphatase activity did not increase in response to inflammatory mediators, but PPi production fell, reflecting lower ectonucleotide pyrophosphatase activity in cells and matrix vesicles. Because PPi is the major physiological inhibitor of mineralization, its decline generated permissive conditions for hydroxyapatite formation. This is in contrast to MSCs treated with dexamethasone, where PPi levels did not fall and mineralization was fuelled by a large and rapid increase in alkaline phosphatase activity. Bone sialoprotein was the only osteoblast marker strongly induced by IL-1β; thus these cells do not become osteoblasts despite depositing abundant mineral. RT-PCR did not detect transcripts indicative of alternative mesenchymal lineages, including chondrocytes, myoblasts, adipocytes, ligament, tendon, or vascular smooth muscle cells. IL-1β phosphorylated multiple MAPKs and activated nuclear factor-κB (NF-κB). Certain inhibitors of MAPK and PI3K, but not NF-κB, prevented mineralization. The findings are of importance to soft tissue mineralization, tissue engineering, and regenerative medicine. PMID:23970554

Enzyme replacement therapy for murine hypophosphatasia.

PubMed

Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

2008-06-01

Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2-/-), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, microCT, and histomorphometry. Akp2-/- mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2-/- mice.

Enzyme Replacement Therapy for Murine Hypophosphatasia*

PubMed Central

Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

2008-01-01

Introduction Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5`-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Materials and Methods Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2−/−), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, μCT, and histomorphometry. Results Akp2−/− mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2−/− mice. PMID:18086009

A facile bacterial assisted electrochemical self-assembly of polypyrrole micro-pillars: towards underwater low adhesive superoleophobicity

NASA Astrophysics Data System (ADS)

Cheng, Zhe; Ding, Chunmei; Liu, Huan; Zhu, Ying; Jiang, Lei

2013-12-01

By taking advantage of bacterial extracellular electron transfer behavior, a facile method was developed to fabricate oriented polypyrrole micro-pillars (PPy-MP) with nanoscale surface roughness. Microbes acted as a living conductive template on which PPy was in situ polymerized. The as-prepared PPy-MP exhibit the distinctive underwater low adhesive superoleophobicity which is attributable to the unique hierarchical micro/nano-structures and the high surface energy by doping with inorganic small anions.By taking advantage of bacterial extracellular electron transfer behavior, a facile method was developed to fabricate oriented polypyrrole micro-pillars (PPy-MP) with nanoscale surface roughness. Microbes acted as a living conductive template on which PPy was in situ polymerized. The as-prepared PPy-MP exhibit the distinctive underwater low adhesive superoleophobicity which is attributable to the unique hierarchical micro/nano-structures and the high surface energy by doping with inorganic small anions. Electronic supplementary information (ESI) available: The shape of a water drop on PPy-MPA and cauliflower-like PPy film in air. See DOI: 10.1039/c3nr03788f

"Let's get down to business: a validation study of the Psychopathic Personality Inventory among a sample of MBA students.".

PubMed

Heinze, Peter; Allen, Rhianon; Magai, Carol; Ritzler, Barry

2010-08-01

While the Psychopathic Personality Inventory (PPI) has gained increasing attention as a measure of noncriminal psychopathy, absent has been research involving samples including business people. This study investigated the validity of the PPI with such a population by examining the association between psychopathic traits and moral decision-making among MBA students. Sixty-six MBA students were assessed using the PPI, the MACH-IV (a measure of Machiavellianism), the Ethical Position Questionnaire (EPQ), and the Defining Issues Test (DIT-2). Only PPI Machiavellian Egocentricity was associated with level of post-conventional moral reasoning. MACH-IV Machiavellianism was a stronger predictor of the Subjectivist ethical position than were PPI subscales. However, a combination of MACH-IV Machiavellianism and four PPI scales accounted for 46% of the variance in Subjectivism. Results suggested that Machiavellian Egocentricity and Machiavellianism are distinct constructs. Benning, Patrick, Hicks, Blonigen, & Krueger (2003)'s two factor model of the PPI was also supported. In general, the findings provided further validation for the PPI as a tool for assessing psychopathic traits among "mainstream" individuals, including business people.

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease

PubMed Central

Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won; Incheon

2018-01-01

Background/Aims The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). Methods GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. Results The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Conclusions Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms. PMID:29069891

Hierarchical carbon nanopetal/polypyrrole nanocomposite electrodes with brush-like architecture for supercapacitors.

PubMed

Cherusseri, Jayesh; Kar, Kamal K

2016-03-28

Hierarchical 3D nanocomposite electrodes with tube brush-like morphology are synthesized by electrochemically depositing polypyrrole (PPY) on carbon nanopetal (CNP) coated carbon fibers (CFs). Initially CNPs are synthesized on CF substrate by chemical vapour deposition. The CNPs synthesized on CF (CNPCF) are further used as an electrically conducting large surface area bearing template for the electropolymerization of PPY in order to fabricate CNPCF-PPY nanocomposite electrodes for supercapacitors (SCs). The CF in CNPCF-PPY nanocomposite functions as (i) a mechanical support for the CNPs, (ii) a current collector for the SC cell and also (iii) to prevent the agglomeration of CNPs within the CNPCF-PPY nanocomposite. Transmission electron microscopy and scanning electron microscopy are used to examine the surface morphology of CNPCF-PPY nanocomposites. The chemical structure of the nanocomposites is analysed by Fourier transform infrared spectroscopy. X-Ray photoelectron spectroscopy has been used to understand the chemical bonding states of the hierarchical CNPCF-PPY nanocomposites. The electrochemical properties of symmetric type CNPCF-PPY SC cells are examined by electrochemical impedance spectroscopy, cyclic voltammetry and galvanostatic charge-discharge measurements. The hierarchical CNPCF-PPY SC exhibits a maximum gravimetric capacitance of 280.4 F g(-1) and an area specific capacitance of 210.3 mF cm(-2) at a current density of 0.42 mA cm(-2). The CNPCF-PPY SC cell exhibits good cycling stability of more than 5000 cycles. The present study proclaims the development of a novel lightweight SC with high-performance.

PPy/PMMA/PEG-based sensor for low-concentration acetone detection

NASA Astrophysics Data System (ADS)

Daneshkhah, A.; Shrestha, S.; Agarwal, M.; Varahramyan, K.

2014-05-01

A polymer pellet-based sensor device comprised of polypyrrole (PPy), polymethyl methacrylate (PMMA) and polyethylene glycol (PEG), its fabrication methods, and the experimental results for low-concentration acetone detection are presented. The design consists of a double layer pellet, where the top layer consists of PPy/PMMA and the bottom layer is composed of PPy/PMMA/PEG. Both sets of material compositions are synthesized by readily realizable chemical polymerization techniques. The mechanism of the sensor operation is based on the change in resistance of PPy and the swelling of PMMA when exposed to acetone, thereby changing the resistance of the layers. The resistances measured on the two layers, and across the pellet, are taken as the three output signals of the sensor. Because the PPy/PMMA and PPy/PMMA/PEG layers respond differently to acetone, as well as to other volatile organic compounds, it is demonstrated that the three output signals can allow the presented sensor to have a better sensitivity and selectivity than previously reported devices. Materials characterizations show formation of new composite with PPy/PMMA/PEG. Material response at various concentrations of acetone was conducted using quartz crystal microbalance (QCM). It was observed that the frequency decreased by 98 Hz for 290 ppm of acetone and by 411 Hz for 1160 ppm. Experimental results with a double layer pellet of PPy/PMMA and PPy/PMMA/PEG show an improved selectivity of acetone over ethanol. The reported acetone sensor is applicable for biomedical and other applications.

MitoPark mice, an animal model of Parkinson's disease, show enhanced prepulse inhibition of acoustic startle and no loss of gating in response to the adenosine A(2A) antagonist SCH 412348.

PubMed

Grauer, Steven M; Hodgson, Robert; Hyde, Lynn A

2014-04-01

Psychoses are debilitating side effects associated with current dopaminergic treatments for Parkinson's disease (PD). Prepulse inhibition (PPI), in which a non-startling stimulus reduces startle response to a subsequent startle-eliciting stimulus, is important in filtering out extraneous sensory stimuli. PPI deficits induced by dopamine agonists can model symptoms of psychosis. Adenosine A(2A) receptor antagonists, being developed as novel PD treatments, indirectly modulate dopamine signaling in the basal ganglia and may have an improved psychosis profile which could be detected using the PPI model. The aims of this study is to characterize PPI in MitoPark mice, which exhibit progressive loss of dopamine signaling and develop a Parkinson-like motor phenotype, and assess standard and novel PD treatment effects on PPI in MitoPark mice, which more closely mimic the basal ganglia dopamine status of PD patients. MitoPark mice displayed enhanced PPI as dopamine tone decreased with age, consistent with studies in intact mice that show enhanced PPI in response to dopamine antagonists. Paradoxically, older MitoParks were more sensitive to PPI disruption when challenged with dopamine agonists such as apomorphine or pramipexole. Alternatively, SCH 412348, an adenosine A(2A) antagonist, did not disrupt PPI in MitoPark mice at doses that normalized hypoactivity. Use of MitoPark mice in the PPI assay to assess the potential for PD treatment to produce psychoses likely represents a more disease-relevant model. SCH 412348 does not differentially disrupt PPI as do dopamine agonists, perhaps indicative of an improved psychosis profile of adenosine A(2A) antagonists, even in PD patients with decreased dopamine tone in the basal ganglia.

Improvement of the overall performances of LiMn{sub 2}O{sub 4} via surface-modification by polypyrrole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ting; Wang, Wan; Zhu, Ding

2015-11-15

Graphical abstract: Polypyrrole(PPy) film has improved the rate performance of LiMn{sub 2}O{sub 4} efficiently due to its excellent conductivity. PPy@LiMn{sub 2}O{sub 4} could provide more energy under the higher power than pristine LMO. - Highlights: • The PPy layer on the surface of LMO particles hasn’t been studied in LiMn{sub 2}O{sub 4} so far. • The solvent in the synthesis process of PPy@LMO is absolute ethyl alcohol. • The differences of surface-modification between the PPy and PI for LMO. • The analyses of rate performances are through specific power. - Abstract: Polypyrrole (PPy) is an excellent conductive polymer and themore » study on its utilization in the surface modification of the LiMn{sub 2}O{sub 4} (LMO) is few. In this work, the structure, morphology and electrochemical performance of surface-modified LiMn{sub 2}O{sub 4} composites with PPy and polyimides (PI) were discussed. The crystal structure, chemical bonds and morphology were characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), respectively. Moreover, the specific power and cycling performance were tested at room and high (55 °C) temperature. The PPy@LMO (surface-modified LMO composites with PPy) shows better performances than the pristine LMO. The addition of PPy not only weakens the corrosion caused by electrolyte, but also improves the discharge capacity at higher rates. The charge transfer resistance of the PPy@LMO is much lower than that of the pristine LMO after cycling.« less

THE REELIN RECEPTORS VLDLR AND ApoER2 REGULATE SENSORIMOTOR GATING IN MICE

PubMed Central

Barr, Alasdair M.; Fish, Kenneth N.; Markou, Athina

2007-01-01

Summary Postmortem brain loss of reelin is noted in schizophrenia patients. Accordingly, heterozygous reeler mutant mice have been proposed as a putative model of this disorder. Little is known, however, about the involvement of the two receptors for reelin, Very-Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), on pre-cognitive processes of relevance to deficits seen in schizophrenia. Thus, we evaluated sensorimotor gating in mutant mice heterozygous or homozygous for the two reelin receptors. Mutant mice lacking one of these reelin receptors were tested for prepulse inhibition (PPI) of the acoustic startle reflex prior to and following puberty, and on a crossmodal PPI task, involving the presentation of acoustic and tactile stimuli. Furthermore, because schizophrenia patients show increased sensitivity to N-methyl-D-aspartate (NMDA) receptor blockade, we assessed the sensitivity of these mice to the PPI-disruptive effects of the NMDA receptor antagonist phencyclidine. The results demonstrated that acoustic PPI did not differ between mutant and wildtype mice. However, VLDLR homozygous mice displayed significant deficits in crossmodal PPI, while ApoER2 heterozygous and homozygous mice displayed significantly increased crossmodal PPI. Both ApoER2 and VLDLR heterozygous and homozygous mice exhibited greater sensitivity to the PPI-disruptive effects of phencyclidine than wildtype mice. These results indicate that partial or complete loss of either one of the reelin receptors results in a complex pattern of alterations in PPI function that include alterations in crossmodal, but not acoustic, PPI and increased sensitivity to NMDA receptor blockade. Thus, reelin receptor function appears to be critically involved in crossmodal PPI and the modulation of the PPI response by NMDA receptors. These findings have relevance to a range of neuropsychiatric disorders that involve sensorimotor gating deficits, including schizophrenia.. PMID:17261317

RNA sequencing confirms similarities between PPI-responsive oesophageal eosinophilia and eosinophilic oesophagitis.

PubMed

Peterson, K A; Yoshigi, M; Hazel, M W; Delker, D A; Lin, E; Krishnamurthy, C; Consiglio, N; Robson, J; Yandell, M; Clayton, F

2018-06-04

Although current American guidelines distinguish proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) from eosinophilic oesophagitis (EoE), these entities are broadly similar. While two microarray studies showed that they have similar transcriptomes, more extensive RNA sequencing studies have not been done previously. To determine whether RNA sequencing identifies genetic markers distinguishing PPI-REE from EoE. We retrospectively examined 13 PPI-REE and 14 EoE biopsies, matched for tissue eosinophil content, and 14 normal controls. Patients and controls were not PPI-treated at the time of biopsy. We did RNA sequencing on formalin-fixed, paraffin-embedded tissue, with differential expression confirmation by quantitative polymerase chain reaction (PCR). We validated the use of formalin-fixed, paraffin-embedded vs RNAlater-preserved tissue, and compared our formalin-fixed, paraffin-embedded EoE results to a prior EoE study. By RNA sequencing, no genes were differentially expressed between the EoE and PPI-REE groups at the false discovery rate (FDR) ≤0.01 level. Compared to normal controls, 1996 genes were differentially expressed in the PPI-REE group and 1306 genes in the EoE group. By less stringent criteria, only MAPK8IP2 was differentially expressed between PPI-REE and EoE (FDR = 0.029, 2.2-fold less in EoE than in PPI-REE), with similar results by PCR. KCNJ2, which was differentially expressed in a prior study, was similar in the EoE and PPI-REE groups by both RNA sequencing and real-time PCR. Eosinophilic oesophagitis and PPI-REE have comparable transcriptomes, confirming that they are part of the same disease continuum. © 2018 John Wiley & Sons Ltd.

Novel degradable co-polymers of polypyrrole support cell proliferation and enhance neurite out-growth with electrical stimulation.

PubMed

Durgam, Hymavathi; Sapp, Shawn; Deister, Curt; Khaing, Zin; Chang, Emily; Luebben, Silvia; Schmidt, Christine E

2010-01-01

Synthetic polymers such as polypyrrole (PPy) are gaining significance in neural studies because of their conductive properties. We evaluated two novel biodegradable block co-polymers of PPy with poly(epsilon-caprolactone) (PCL) and poly(ethyl cyanoacrylate) (PECA) for nerve regeneration applications. PPy-PCL and PPy-PECA co-polymers can be processed from solvent-based colloidal dispersions and have essentially the same or greater conductivity (32 S/cm for PPy-PCL, 19 S/cm for PPy-PECA) compared to the PPy homo-polymer (22 S/cm). The PPy portions of the co-polymers permit electrical stimulation whereas the PCL or PECA blocks enable degradation by hydrolysis. For in vitro tests, films were prepared on polycarbonate sheets by air brushing layers of dispersions and pressing the films. We characterized the films for hydrolytic degradation, electrical conductivity, cell proliferation and neurite extension. The co-polymers were sufficient to carry out electrical stimulation of cells without the requirement of a metallic conductor underneath the co-polymer film. In vitro electrical stimulation of PPy-PCL significantly increased the number of PC12 cells bearing neurites compared to unstimulated PPy-PCL. For in vivo experiments, the PPy co-polymers were coated onto the inner walls of nerve guidance channels (NGCs) made of the commercially available non-conducting biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV). The NGCs were implanted in a 10 mm defect made in the sciatic nerve of rats, and harvested after 8 weeks. Histological staining showed axonal growth. The studies indicated that these new conducting degradable biomaterials have good biocompatibility and support proliferation and growth of PC12 cells in vitro (with and without electrical stimulation) and neurons in vivo (without electrical stimulation).

Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer

PubMed Central

Makondi, Precious Takondwa; Lee, Chia-Hwa; Huang, Chien-Yu; Chu, Chi-Ming; Chang, Yu-Jia

2018-01-01

Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID). Protein–protein interaction (PPI) networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING) and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs); the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1, early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4) revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS). The identified genes and pathways can be potential targets and predictors of therapeutic resistance and prognosis in bevacizumab-treated patients with mCRC. PMID:29342159

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

PubMed

de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

2015-06-01

Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Pacemaker implantation rate after transcatheter aortic valve implantation with early and new-generation devices: a systematic review.

PubMed

van Rosendael, Philippe J; Delgado, Victoria; Bax, Jeroen J

2018-06-01

The incidence of new-onset conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) with new-generation prostheses remains debated. This systematic review analyses the incidence of PPI after TAVI with new-generation devices and evaluates the electrical, anatomical, and procedural factors associated with PPI. In addition, the incidence of PPI after TAVI with early generation prostheses was reviewed for comparison. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, this systematic review screened original articles published between October 2010 and October 2017, reporting on the incidence of PPI after implantation of early and new-generation TAVI prostheses. Of the 1406 original articles identified in the first search for new-generation TAVI devices, 348 articles were examined for full text, and finally, 40 studies (n = 17 139) were included. The incidence of a PPI after the use of a new-generation TAVI prosthesis ranged between 2.3% and 36.1%. For balloon-expandable prostheses, the PPI rate remained low when using an early generation SAPIEN device (ranging between 2.3% and 28.2%), and with the new-generation SAPIEN 3 device, the PPI rate was between 4.0% and 24.0%. For self-expandable prostheses, the PPI rates were higher with the early generation CoreValve device (16.3-37.7%), and despite a reduction in PPI rates with the new Evolut R, the rates remained relatively higher (14.7-26.7%). When dividing the studies according to the highest (>26.0%) and the lowest (<12.1%) quintile of PPI rate, patients within the highest quintile were more frequently women when compared with the lowest quintile group (50.9% vs. 46.3%, P < 0.001). Pre-existent conduction abnormalities (electrical factor), calcification of the left ventricular outflow tract (anatomical factor), and balloon valvuloplasty and depth of implantation (procedural factors) were associated with increased risk of PPI. The rate of PPI after TAVI with new-generation devices is highly variable. Specific recommendations for implantation of each prosthesis, taking into consideration the presence of pre-existent conduction abnormalities and anatomical factors, may be needed to reduce the risk of PPI.

[Phosphorescent effect of Ir (ppy)3 on the luminescent characteristic of Rubrene].

PubMed

Xu, Hong-Hua; Xu, Zheng; Zhang, Fu-Jun; Zhao, Su-Ling; Yuan, Guang-Cai; Chen, Yue-Ning

2008-07-01

Many organic matters including heavy metal ions can validly utilize the singlet and triplet for luminescence owiog to the spin-orbit coupling. As a result, the internal quantum efficiency can easily achieve a value higher than traditional organic light emitting diodes in theory. There is a strong luminescence of PVK in PVK : PBD : Rubrene system. PL spectra excited by 345 nm of PVK : PBD : Rubrene thin film has a 410 nm PVK luminescent peak and a 560 nm Rubrene peak. EL still has a PVK luminescent peak, which should be kept from happening. Excitons can not adequately transferred from the matrix solution to Rubrene. The doping with Ir(ppy)3 improves the PVK : PBD : Rubrene system performance. PL spectra excited by 345 nm of PVK : PBD : Ir(ppy)3 : Rubrene with low concentration of Rubrene has a 510 nm Ir(ppy)3 peak and a new 548 nm one. However, the Ir(ppy)3 peak is smaller and the Rubrene one is bigger in EL spectra. Notably a strong and single luminescence of Rubrene is obtained in EL and PL spectra excited by 345 nm of PVK : PBD : Ir(ppy)3 : Rubrene with high concentration of Rubrene. Meanwhile, the Ir(ppy)3 luminescent peak disappears. The mechanism originates from the phosphorescent effect of Ir (ppy)3. The singlet excitons can basically be transferred from PVK : PBD or Ir(ppy)3 to Rubrene. But most excitons from Ir (ppy)3 can directly tunnel to the fluorescent material and come into being singlet states that can return to ground states and cause luminescence. Rubrene can accept proportional excitons with low concentration. While the concentration of Rubrene is higher, excitons can be entirely accepted by Rubrene. The effect also restricts the luminescent intensity of Ir(ppy)3 and boosts up that of Rubrene. Furthermore, the energy transfer in PVK : PBD : Ir(ppy)3 : Rubrene system is primary the Forester energy transfer. Excitation spectra of Rubrene and emission spectra of Ir(ppy)3 have a large overlap revealing that there is a strong energy transfer and further confirmed the phosphorescent effect of Ir(ppy)3. The doping system with phosphorescence material and small molecules can enhance the brightness and internal quantum efficiency.

Impact of constitutional isomers of (BMes(2))phenylpyridine on structure, stability, phosphorescence, and Lewis acidity of mononuclear and dinuclear Pt(II) complexes.

PubMed

Rao, Ying-Li; Wang, Suning

2009-08-17

The impact of two constitutional isomers, 2-(4-BMes(2)-Ph)-pyridine (p-B-ppy, 1) and 5-BMes(2)-2-ph-pyridine (p-ppy-B, 2), as N,C-chelate ligands on the structures, stabilities, electronic and photophysical properties, and Lewis acidities of Pt(II) complexes has been investigated. Six Pt(II) complexes, Pt(p-B-ppy)Ph(DMSO) (1a), Pt(p-B-ppy)Ph(py) (1b), [Pt(p-B-ppy)Ph](2)(4,4'-bipy) (1c), Pt(p-ppy-B)Ph(DMSO) (2a), Pt(p-ppy-B)Ph(py) (2b), and [Pt(p-ppy-B)Ph](2)(4,4'-bipy) (2c), have been synthesized and fully characterized. The structures of 1a, 1c, 2a, and 2c were established by single-crystal X-ray diffraction analysis. All complexes adopt a cis geometry with the phenyl ligand being cis to the phenyl ring of the ppy chelate. The dinuclear complexes 2a and 2c were found to exist in two isomeric forms in solution, syn and anti, with respect to the relative orientation of the two BMes(2) groups in the molecule. While all complexes are stable in solution under ambient air, compound 2a was found to react with H(2)O slowly in solution and form complex 2a-OH, where one of the mesityl groups on the boron center was replaced by an OH group. This instability of 2a is attributed to an internal dimethylsulfoxide-directed hydrolysis process via hydrogen bonds. The electron-accepting ability of the free ligands and the complexes were examined by cyclic voltammetry, establishing that, for p-ppy-B, Pt(II) chelation enhances the electron-accepting ability while, for p-B-ppy, Pt(II) chelation has little impact. All Pt(II) complexes display oxygen-sensitive phosphorescence in solution at ambient temperature, dominated by B-ppy or ppy-B centered pi --> pi* transitions. The Lewis acidity of the complexes was examined by fluoride titration experiments using UV-vis, phosphorescence, and NMR spectroscopic methods, establishing that the p-ppy-B complexes have similar and strong binding constants while the p-B-ppy complexes have a much lower affinity toward F(-), compared to the free ligands. In the dinuclear complexes, weak electronic communication between the two Pt(II) units is evident in 1c but absent in 2c, attributable to the different steric interactions in the two molecules.

Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?

PubMed

Bakshi, Vaishali P; Alsene, Karen M; Roseboom, Patrick H; Connors, Elenora E

2012-02-01

A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post-traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a nociceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24 h, 48 h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to those elicited by corticotropin-releasing factor (CRF; 0.5 and 3 μg/6 μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24 h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the lowdose producing a PPI deficit 24 h after infusion. Interestingly, the high dose also produced a PPI deficit 24 h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits emerged) by both stressors and CRF, but returned to normal control levels 24 h later, when PPI deficits were present. Thus, predator exposure produces a delayed disruption of PPI, and stimulation of CRF receptors recapitulates these effects. Contemporaneous HPA axis activation is neither necessary nor sufficient for these PPI deficits. These results indicate that predator exposure, perhaps acting through CRF, may model the delayed-onset and persistent sensorimotor gating abnormalities that have been observed clinically in PTSD, and that further studies using this model may shed insight on the mechanisms of information-processing deficits in this disorder. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

PubMed

Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki

2014-09-14

The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

SPR Biosensors in Direct Molecular Fishing: Implications for Protein Interactomics.

PubMed

Florinskaya, Anna; Ershov, Pavel; Mezentsev, Yuri; Kaluzhskiy, Leonid; Yablokov, Evgeniy; Medvedev, Alexei; Ivanov, Alexis

2018-05-18

We have developed an original experimental approach based on the use of surface plasmon resonance (SPR) biosensors, applicable for investigation of potential partners involved in protein⁻protein interactions (PPI) as well as protein⁻peptide or protein⁻small molecule interactions. It is based on combining a SPR biosensor, size exclusion chromatography (SEC), mass spectrometric identification of proteins (LC-MS/MS) and direct molecular fishing employing principles of affinity chromatography for isolation of potential partner proteins from the total lysate of biological samples using immobilized target proteins (or small non-peptide compounds) as ligands. Applicability of this approach has been demonstrated within the frame of the Human Proteome Project (HPP) and PPI regulation by a small non-peptide biologically active compound, isatin.

Nanocomposite Prepared from In Situ Grafting of Polypyrrole to Aminobenzoyl-Functionalized Multiwalled Carbon Nanotube and Its Electrochemical Properties

DTIC Science & Technology

2011-01-01

Soxhlet extracted overnight with distilled water and methanol, and finally freeze-dried for 48 h to afford AF-MWCNT. Polymerization of PPy Pyrrole (10.0...Synthesis of PPy-g-MWCNT Composite In the same set-up for the synthesis of PPy, AF-MWCNT (1.0 g), pyrrole (9.0 g, 134 mmol), and 1 M aqueous HCl (120...sites for the covalent attachment of PPy. Thus, the PPy was grafted onto the surface of AF-MWCNT by chemical oxidation polymerization of pyrrole in

Chemically designed Pt/PPy nano-composite for effective LPG gas sensor.

PubMed

Gaikwad, Namrata; Bhanoth, Sreenu; More, Priyesh V; Jain, G H; Khanna, P K

2014-03-07

Simultaneous in situ reduction of hexachloroplatinic acid by the amine group in the pyrrole monomer and oxidation of pyrrole to form polypyrrole (PPy) was examined. The reactions were performed at various temperatures to understand the degree of reduction of platinum precursor as well as doping of polypyrrole with Pt(II) chloro-complex. Spectroscopic images revealed different morphologies for the Pt/PPy nano-composite prepared at various temperatures. The as-prepared Pt/PPy nano-composite samples were tested for their ability to sense liquefied petroleum gas (LPG) which resulted in excellent sensing at relatively low temperature. The porous nature and ohmic contact between the PPy and platinum nanoparticles makes the as-prepared Pt/PPy nano-composite highly useful for sensors as well as electronic applications.

The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data.

PubMed

Zhang, Chaoyang; Peng, Li; Zhang, Yaqin; Liu, Zhaoyang; Li, Wenling; Chen, Shilian; Li, Guancheng

2017-06-01

Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched. Cytoscape software was for the construction of protein-protein interaction (PPI) network and module analysis to find the hub genes and key pathways. Finally, weighted correlation network analysis (WGCNA) was conducted to further screen critical gene modules with similar expression pattern and explore their biological significance. Significance analysis identified 1230 DEGs with fold change >2, including 632 significantly down-regulated DEGs and 598 significantly up-regulated DEGs. GO term enrichment analysis suggested that up-regulated DEG significantly enriched in immune response, cell adhesion, cell migration, type I interferon signaling pathway, and cell proliferation, and the down-regulated DEG mainly enriched in response to endoplasmic reticulum stress and endoplasmic reticulum unfolded protein response. KEGG pathway analysis found DEGs significantly enriched in five pathways including complement and coagulation cascades, focal adhesion, ECM-receptor interaction, antigen processing and presentation, and protein processing in endoplasmic reticulum. The top 10 hub genes in HCC were separately GMPS, ACACA, ALB, TGFB1, KRAS, ERBB2, BCL2, EGFR, STAT3, and CD8A, which resulted from PPI network. The top 3 gene interaction modules in PPI network enriched in immune response, organ development, and response to other organism, respectively. WGCNA revealed that the confirmed eight gene modules significantly enriched in monooxygenase and oxidoreductase activity, response to endoplasmic reticulum stress, type I interferon signaling pathway, processing, presentation and binding of peptide antigen, cellular response to cadmium and zinc ion, cell locomotion and differentiation, ribonucleoprotein complex and RNA processing, and immune system process, respectively. In conclusion, we identified some key genes and pathways closely related with HCC initiation and progression by a series of bioinformatics analysis on DEGs. These screened genes and pathways provided for a more detailed molecular mechanism underlying HCC occurrence and progression, holding promise for acting as biomarkers and potential therapeutic targets.

Identification and functional analysis of risk-related microRNAs for the prognosis of patients with bladder urothelial carcinoma.

PubMed

Gao, Ji; Li, Hongyan; Liu, Lei; Song, Lide; Lv, Yanting; Han, Yuping

2017-12-01

The aim of the present study was to investigate risk-related microRNAs (miRs) for bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression data downloaded from the Cancer Genome Atlas were utilized for survival analysis. Risk factor estimation was performed using Cox's proportional regression analysis. A microRNA-regulated target gene network was constructed and presented using Cytoscape. In addition, the Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, followed by protein-protein interaction (PPI) network analysis. Finally, the K-clique method was applied to analyze sub-pathways. A total of 16 significant microRNAs, including hsa-miR-3622a and hsa-miR-29a, were identified (P<0.05). Following Cox's proportional regression analysis, hsa-miR-29a was screened as a prognostic marker of BUC risk (P=0.0449). A regulation network of hsa-miR-29a comprising 417 target genes was constructed. These target genes were primarily enriched in GO terms, including collagen fibril organization, extracellular matrix (ECM) organization and pathways, such as focal adhesion (P<0.05). A PPI network including 197 genes and 510 interactions, was constructed. The top 21 genes in the network module were enriched in GO terms, including collagen fibril organization and pathways, such as ECM receptor interaction (P<0.05). Finally, 4 sub-pathways of cysteine and methionine metabolism, including paths 00270_4, 00270_1, 00270_2 and 00270_5, were obtained (P<0.01) and identified to be enriched through DNA (cytosine-5)-methyltransferase ( DNMT)3A, DNMT3B , methionine adenosyltransferase 2α ( MAT2A ) and spermine synthase ( SMS ). The identified microRNAs, particularly hsa-miR-29a and its 4 associated target genes DNMT3A, DNMT3B, MAT2A and SMS , may participate in the prognostic risk mechanism of BUC.

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

PubMed Central

Hong, Donghyun; Rohani Rankouhi, Seyedmorteza; Wiltfang, Jens; Fernández, Guillén; Norris, David G.; Tendolkar, Indira

2018-01-01

Abstract The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long‐term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ‐aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face–name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory‐related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory‐related functional connectivity in a medial prefrontal–thalamus–hippocampus network. PMID:29488277

ImmunemiR - A Database of Prioritized Immune miRNA Disease Associations and its Interactome.

PubMed

Prabahar, Archana; Natarajan, Jeyakumar

2017-01-01

MicroRNAs are the key regulators of gene expression and their abnormal expression in the immune system may be associated with several human diseases such as inflammation, cancer and autoimmune diseases. Elucidation of miRNA disease association through the interactome will deepen the understanding of its disease mechanisms. A specialized database for immune miRNAs is highly desirable to demonstrate the immune miRNA disease associations in the interactome. miRNAs specific to immune related diseases were retrieved from curated databases such as HMDD, miR2disease and PubMed literature based on MeSH classification of immune system diseases. The additional data such as miRNA target genes, genes coding protein-protein interaction information were compiled from related resources. Further, miRNAs were prioritized to specific immune diseases using random walk ranking algorithm. In total 245 immune miRNAs associated with 92 OMIM disease categories were identified from external databases. The resultant data were compiled as ImmunemiR, a database of prioritized immune miRNA disease associations. This database provides both text based annotation information and network visualization of its interactome. To our knowledge, ImmunemiR is the first available database to provide a comprehensive repository of human immune disease associated miRNAs with network visualization options of its target genes, protein-protein interactions (PPI) and its disease associations. It is freely available at http://www.biominingbu.org/immunemir/. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Curcumin may serve an anticancer role in human osteosarcoma cell line U-2 OS by targeting ITPR1.

PubMed

Luo, Zhanpeng; Li, Dawei; Luo, Xiaobo; Li, Litao; Gu, Suxi; Yu, Long; Ma, Yuanzheng

2018-04-01

The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes. Then, the mRNA levels of key genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in U-2 OS cells. Finally, cell apoptosis, proliferation, migration and invasion arrays were performed. In total, 201 DEGs were identified in the curcumin-treated group. EEF1A1 (degree=88), ATF7IP, HIF1A, SMAD7, CLTC, MCM10, ITPR1, ADAM15, WWP2 and ATP5C1, which were enriched in 'biological process', exhibited higher degrees than other genes in the PPI network. RT-qPCR demonstrated that treatment with curcumin was able to significantly increase the levels of CLTC and ITPR1 mRNA in curcumin-treated cells compared with control. In addition, targeting ITPR1 with curcumin significantly promoted apoptosis and suppressed proliferation, migration and invasion. Targeting ITPR1 via curcumin may serve an anticancer role by mediating apoptosis, proliferation, migration and invasion in U-2 OS cells.

The Indications, Applications, and Risks of Proton Pump Inhibitors.

PubMed

Mössner, Joachim

2016-07-11

Proton pump inhibitors (PPI) are the most effective drugs for inhibiting gastric acid secretion. They have been in clinical use for more than 25 years, In 2014, 3.475 billion daily defined doses (DDD) of PPI were prescribed in Germany. This high number alone calls for a critical analysis of the spectrum of indications for PPI and their potential adverse effects. This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane Library databases, with particular emphasis on randomized, prospective multicenter trials, cohort studies, case-control studies, and meta-analyses. The inhibition of gastric acid secretion with PPI is successfully used for the treatment of gastroesophageal reflux disease and of gastric and duodenal ulcers, for the secondary prevention of gastroduodenal lesions that have arisen under treatment with nonsteroidal anti-inflammatory drugs and acetylsalicylic acid, and for the prevention of recurrent hemorrhage from ulcers after successful endoscopic hemostasis. PPI are given along with practically all antibiotic regimens for the eradication of Helicobacter pylori infection. The number of prescriptions for PPI has risen linearly over the past 25 years. As there has been no broadening of indications, one may well ask whether the current, extensive use of PPI is justified. There is evidence that patients taking PPI are at greater risk for fractures. Moreover, the vitamin B12 level should be checked occasionally in all patients taking PPI. PPI are among the more effective drugs for the treatment of diseases associated with gastric acid. In view of their cost and potential adverse effects, they should only be prescribed for scientifically validated indications.

Is it worth it? Patient and public views on the impact of their involvement in health research and its assessment: a UK-based qualitative interview study.

PubMed

Crocker, Joanna C; Boylan, Anne-Marie; Bostock, Jennifer; Locock, Louise

2017-06-01

There are mounting calls for robust, critical evaluation of the impact of patient and public involvement (PPI) in health research. However, questions remain about how to assess its impact, and whether it should be assessed at all. The debate has thus far been dominated by professionals. To explore the views of PPI contributors involved in health research regarding the impact of PPI on research, whether and how it should be assessed. Qualitative interview study. Thirty-eight PPI contributors involved in health research across the UK. Participants felt that PPI has a beneficial impact on health research. They described various impactful roles, which we conceptualize as the 'expert in lived experience', the 'creative outsider', the 'free challenger', the 'bridger', the 'motivator' and the 'passive presence'. Participants generally supported assessing the impact of PPI, while acknowledging the challenges and concerns about the appropriateness and feasibility of measurement. They expressed a range of views about what impacts should be assessed, by whom and how. Individual feedback on impact was seen as an important driver of improved impact and motivation to stay involved. While there appears to be widespread support for PPI impact assessment among PPI contributors, their views on what to assess and how are diverse. PPI contributors should be involved as equal partners in debates and decisions about these issues. Individual feedback on impact may increase PPI contributors' potential impact and their motivation to stay involved. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

Gastroprotective strategies in chronic NSAID users: a cost-effectiveness analysis comparing single-tablet formulations with individual components.

PubMed

de Groot, N L; Spiegel, B M R; van Haalen, H G M; de Wit, N J; Siersema, P D; van Oijen, M G H

2013-01-01

To evaluate the cost-effectiveness of competing gastroprotective strategies, including single-tablet formulations, in the prevention of gastrointestinal (GI) complications in patients with chronic arthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs). We performed a cost-utility analysis to compare eight gastroprotective strategies including NSAIDs, cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol, and single-tablet formulations. We derived estimates for outcomes and costs from medical literature. The primary outcome was incremental cost per quality-adjusted life-year gained. We performed sensitivity analyses to assess the effect of GI complications, compliance rates, and drug costs. For average-risk patients, NSAID + PPI cotherapy was most cost-effective. The NSAID/PPI single-tablet formulation became cost-effective only when its price decreased from €0.78 to €0.56 per tablet, or when PPI compliance fell below 51% in the NSAID + PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the GI complication risk, costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In patients with a threefold higher risk of GI complications, both NSAID + PPI cotherapy and single-tablet formulation were cost-effective. NSAID + PPI cotherapy is the most cost-effective strategy in all patients with chronic arthritis irrespective of their risk for GI complications. For patients with increased GI risk, the NSAID/PPI single-tablet formulation is also cost-effective. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Increased functional connectivity with puberty in the mentalising network involved in social emotion processing

PubMed Central

Klapwijk, Eduard T.; Goddings, Anne-Lise; Heyes, Stephanie Burnett; Bird, Geoffrey; Viner, Russell M.; Blakemore, Sarah-Jayne

2015-01-01

There is increasing evidence that puberty plays an important role in the structural and functional brain development seen in adolescence, but little is known of the pubertal influence on changes in functional connectivity. We explored how pubertal indicators (salivary concentrations of testosterone, oestradiol and DHEA; pubertal stage; menarcheal status) relate to functional connectivity between components of a mentalising network identified to be engaged in social emotion processing by our prior work, using psychophysiological interaction (PPI) analysis. Female adolescents aged 11 to 13 years were scanned whilst silently reading scenarios designed to evoke either social emotions (guilt and embarrassment) or basic emotions (disgust and fear), of which only social compared to basic emotions require the representation of another person’s mental states. Pubertal stage and menarcheal status were used to assign participants to pre/early or mid/late puberty groups. We found increased functional connectivity between the dorsomedial prefrontal cortex (DMPFC) and the right posterior superior temporal sulcus (pSTS) and right temporo-parietal junction (TPJ) during social relative to basic emotion processing. Moreover, increasing oestradiol concentrations were associated with increased functional connectivity between the DMPFC and the right TPJ during social relative to basic emotion processing, independent of age. Our analysis of the PPI data by phenotypic pubertal status showed that more advanced puberty stage was associated with enhanced functional connectivity between the DMPFC and the left anterior temporal cortex (ATC) during social relative to basic emotion processing, also independent of age. Our results suggest increased functional maturation of the social brain network with the advancement of puberty in girls. PMID:23998674

Key genes and pathways in measles and their interaction with environmental chemicals

PubMed Central

Zhang, Rongqiang; Jiang, Hualin; Li, Fengying; Su, Ning; Ding, Yi; Mao, Xiang; Ren, Dan; Wang, Jing

2018-01-01

The aim of the present study was to explore key genes that may have a role in the pathology of measles virus infection and to clarify the interaction networks between environmental factors and differentially expressed genes (DEGs). After screening the database of the Gene Expression Omnibus of the National Center for Biotechnology Information, the dataset GSE5808 was downloaded and analyzed. A global normalization method was performed to minimize data inconsistencies and heterogeneity. DEGs during different stages of measles virus infection were explored using R software (v3.4.0). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs were performed using Cytoscape 3.4.0 software. A protein-protein interaction (PPI) network of the DEGs was obtained from the STRING database v9.05. A total of 43 DEGs were obtained from four analyzed sample groups, including 10 highly expressed genes and 33 genes with decreased expression. The most enriched pathways based on KEGG analysis were fatty acid elongation, cytokine-cytokine receptor interaction and RNA degradation. The genes mentioned in the PPI network were mainly associated with protein binding and chemokine activity. A total of 219 chemicals were identified that may, jointly or on their own, interact with the 6 DEGs between the control group and patients with measles (at hospital entry), including benzo(a)pyrene (BaP) and tetrachlorodibenzodioxin (TCDD). In conclusion, the present study revealed that chemokines and environmental chemicals, e.g. BaP and TCDD, may affect the development of measles. PMID:29805511

Esophageal motor dysfunction plays a key role in GERD with globus sensation--analysis of factors promoting resistance to PPI therapy.

PubMed

Tsutsui, Hideaki; Manabe, Noriaki; Uno, Masako; Imamura, Hiroshi; Kamada, Tomoari; Kusunoki, Hiroaki; Shiotani, Akiko; Hata, Jiro; Harada, Tamotsu; Haruma, Ken

2012-09-01

Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.

Sustaining patient and public involvement in research: A case study of a research centre

PubMed Central

Jinks, Clare; Carter, Pam; Rhodes, Carol; Beech, Roger; Dziedzic, Krysia; Hughes, Rhian; Blackburn, Steven; Ong, Bie Nio

2013-01-01

The literature on patient and public involvement (PPI) in research covers a wide range of topics. However, one area of investigation that appears under developed is the sustainability and impact of PPI beyond involvement in time-limited research projects. This paper presents a case study of PPI development in one primary care research centre in England, and its approach to making this sustainable using documentary sources and material from a formal evaluation. We provide narrative accounts of the set-up, operation and main processes of PPI, and its perceived impact. PPI requires a long-term perspective with participation and trust growing over time, and both users and researchers learning what approaches work best. PPI is a complex interplay of clarity of purpose, defined roles and relationships, organised support (paid PPI staff) and a well-funded infrastructure. ‘Soft systems’ are equally important such as flexible and informal approaches to meetings, adapting timetables and environments to meet the needs of lay members and to create spaces for relationships to develop between researchers and lay members that are based on mutual trust and respect. This case study highlights that the right combination of ethos, flexible working practices, leadership, and secure funding goes a long way to embedding PPI beyond ad hoc involvement. This allows PPI in research to be integrated in the infrastructure and sustainable. PMID:26705412

Patient and public involvement: how much do we spend and what are the benefits?

PubMed

Pizzo, Elena; Doyle, Cathal; Matthews, Rachel; Barlow, James

2015-12-01

Patient and public involvement (PPI) is seen as a way of helping to shape health policy and ensure a patient-focused health-care system. While evidence indicates that PPI can improve health-care decision making, it also consumes monetary and non-monetary resources. Given the financial climate, it is important to start thinking about the costs and benefits of PPI and how to evaluate it in economic terms. We conducted a literature review to assess the potential benefits and costs of involvement and the challenges in carrying out an economic evaluation of PPI. The benefits of PPI include effects on the design of new projects or services, on NHS governance, on research design and implementation and on citizenship and equity. Economic evaluation of PPI activities is limited. The lack of an appropriate analytical framework, data recording and understanding of the potential costs and benefits of PPI, especially from participants' perspectives, represent serious constraints on the full evaluation of PPI. By recognizing the value of PPI, health-care providers and commissioners can embed it more effectively within their organizations. Better knowledge of costs may prompt organizations to effectively plan, execute, evaluate and target resources. This should increase the likelihood of more meaningful activity, avoid tokenism and enhance organizational efficiency and reputation. © 2014 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Polypyrrole/sargassum activated carbon modified stainless-steel sponge as high-performance and low-cost bioanode for microbial fuel cells

NASA Astrophysics Data System (ADS)

Wu, Gaoming; Bao, Han; Xia, Zheng; Yang, Bin; Lei, Lecheng; Li, Zhongjian; Liu, Chunxian

2018-04-01

Anode materials, as the core component of microbial fuel cells (MFCs), have huge impacts on power generation performance and overall cost. Stainless-steel sponge (SS) can be a promising material for MFC anodes, due to its open continuous three-dimensional structure, high conductivity and low cost. However, poor biocompatibility limits its application. In this paper, a polypyrrole/sargassum activated carbon modified SS anode (Ppy/SAC/SS) is developed by electrochemical polymerization of pyrrole on the SS with the SAC as a dopant. The maximum power density achieved with the Ppy/SAC/SS anode is 45.2 W/m3, which is increased by 2 orders of magnitude and 2.9 times compared with an unmodified SS anode and a solely Ppy modified SS anode (Ppy/SS), respectively. In addition, the Ppy/SAC layer effectively eliminates electrochemical corrosion of the SS substrate. Electrochemical impedance spectroscopy reveals that Ppy/SAC modification decreases electron transfer resistance between the bacteria and the electrode. Furthermore, in vivo fluorescence imaging indicates that a more uniform biofilm is formed on the Ppy/SAC/SS compared to the unmodified SS and Ppy/SS. Due to the low cost of the materials, easy fabrication process and relatively high performance, our developed Ppy/SAC/SS can be a cost efficient anode material for MFCs in practical applications.

Hyperbranched-dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

NASA Astrophysics Data System (ADS)

Alavi, Seyyed Jamal; Gholami, Leila; Askarian, Saeedeh; Darroudi, Majid; Massoudi, Abdolhossein; Rezaee, Mehdi; Kazemi Oskuee, Reza

2017-02-01

The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate-PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI-PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI-PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)-dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

Proton-pump inhibitor use is associated with low serum magnesium concentrations

PubMed Central

Danziger, John; William, Jeffrey H.; Scott, Daniel J.; Lee, Joon; Lehman, Li-wei; Mark, Roger G.; Howell, Michael D.; Celi, Leo A.; Mukamal, Kenneth J.

2017-01-01

Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (< 1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of neither among 11,490 consecutive adult admissions to an intensive care unit of a tertiary medical center. Of these, 2632 patients reported PPI use prior to admission, while 657 patients were using a histamine-2 receptor antagonist. PPI use was associated with 0.012 mg/dl lower adjusted serum magnesium concentration compared to users of no acid-suppressive medications, but this effect was restricted to those patients taking diuretics. Among the 3286 patients concurrently on diuretics, PPI use was associated with a significant increase of hypomagnesemia (odds ratio 1.54) and 0.028 mg/dl lower serum magnesium concentration. Among those not using diuretics, PPI use was not associated with serum magnesium levels. Histamine-2 receptor antagonist use was not significantly associated with magnesium concentration without or with diuretic use. The use of PPI was not associated with serum phosphate concentration regardless of diuretic use. Thus, we verify case reports of the association between PPI use and hypomagnesemia in those concurrently taking diuretics. Hence, serum magnesium concentrations should be followed in susceptible individuals on chronic PPI therapy. PMID:23325090

Efficacy and Safety of Ultrasound-Guided Percutaneous Polidocanol Sclerotherapy in Benign Cystic Thyroid Nodules: Preliminary Results.

PubMed

Gong, Xiaohua; Zhou, Qi; Wang, Fang; Wu, Wenjun; Chen, Xiaojun

2017-01-01

To evaluate the efficacy and safety of percutaneous polidocanol injection (PPI) in treating cystic thyroid nodules. A total of 158 cystic or predominantly cystic thyroid nodules (>80% cystic component) in 143 patients were evaluated. 114 patients with compressive symptoms or aesthetic complaints were offered PPI. 44 individuals without compressive symptoms and aesthetic complaints who were only followed up clinically were used as the control group. The efficacy and safety of PPI were evaluated for 1 month, 3 months, 6 months, 9 months, and 12 months of follow-up. In the PPI group, the mean baseline volume of 15.6 ± 18.9 cm 3 reduced at the 1-month follow-up to 5.1 ± 5.6 cm 3 ( p < 0.001) and 0.6 ± 0.9 ( p < 0.001), and nodules shrunk according to the time after PPI ( p < 0.001). A complete response (if ≥70% decrease) to PPI at the 12-month follow-up occurred in 100% of the cystic or predominant cystic nodules. None of the nodules recurred at the 12-month follow-up after PPI. The side effects were mild. Twenty patients (17.5%) developed mild localized pain, and fourteen cases (12.3%) experienced mild or moderate fever after PPI. PPI is a safe and effective alternative to treat benign cystic or predominant cystic thyroid nodules.

Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia.

PubMed

Kumari, Veena; Das, Mrigen; Hodgins, Sheilagh; Zachariah, Elizabeth; Barkataki, Ian; Howlett, Michael; Sharma, Tonmoy

2005-03-07

Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

The electrochemical behavior of poly 1-pyrenemethyl methacrylate binder and its effect on the interfacial chemistry of a silicon electrode

NASA Astrophysics Data System (ADS)

Haregewoin, Atetegeb Meazah; Terborg, Lydia; Zhang, Liang; Jurng, Sunhyung; Lucht, Brett L.; Guo, Jinghua; Ross, Philip N.; Kostecki, Robert

2018-02-01

The physico-chemical properties of poly (1-pyrenemethyl methacrylate) (PPy) are presented with respect to its use as a binder in a Si composite anode for Li-ion batteries. PPy thin-films on Si(100) wafer and Cu model electrodes are shown to exhibit superior adhesion as compared to conventional polyvinylidene difluoride (PVdF) binder. Electrochemical testing of the model bi-layer PPy/Si(100) electrodes in a standard organic carbonate electrolyte reveal higher electrolyte reduction current and an overall irreversible cathodic charge consumption during initial cycling versus the uncoated Si electrode. The PPy thin-film is also shown to impede lithiation of the underlying Si. XAS, AFM, TGA and ATR-FTIR analysis indicated that PPy binder is both chemically and electrochemically stable in the cycling potential range however significant swelling is observed due to a selective uptake of diethyl carbonate (DEC) from the electrolyte. The increased concentration of DEC and depletion of ethylene carbonate (EC) at the Si/PPy interface leads to continuous decomposition of the electrolyte and results in non-passivating behavior of the Si(100)/PPy electrode as compared to pristine silicon. Consequently, PPy binder improves the mechanical integrity of composite Si anodes but it influences mass transport at the Si(100)/PPy interface and alters electrochemical response of silicon during cycling in an adverse manner.

Polypyrrole/carbon nanotube nanocomposite enhanced the electrochemical capacitance of flexible graphene film for supercapacitors

NASA Astrophysics Data System (ADS)

Lu, Xiangjun; Dou, Hui; Yuan, Changzhou; Yang, Sudong; Hao, Liang; Zhang, Fang; Shen, Laifa; Zhang, Luojiang; Zhang, Xiaogang

2012-01-01

The flexible electrodes have important potential applications in energy storage of portable electronic devices for their powerful structural properties. In this work, unique flexible films with polypyrrole/carbon nanotube (PPy/CNT) composite homogeneously distributed between graphene (GN) sheets are successfully prepared by flow-assembly of the mixture dispersion of GN and PPy/CNT. In such layered structure, the coaxial PPy/CNT nanocables can not only enlarge the space between GN sheets but also provide pseudo-capacitance to enhance the total capacitance of electrodes. According to the galvanostatic charge/discharge analysis, the mass and volume specific capacitances of GN-PPy/CNT (52 wt% PPy/CNT) are 211 F g-1 and 122 F cm-3 at a current density of 0.2 A g-1, higher than those of the GN film (73 F g-1 and 79 F cm-3) and PPy/CNT (164 F g-1 and 67 F cm-3). Significantly, the GN-PPy/CNT electrode shows excellent cycling stability (5% capacity loss after 5000 cycles) due to the flexible GN layer and the rigid CNT core synergistical releasing the intrinsic differential strain of PPy chains during long-term charge/discharge cycles.

The proton pump inhibitor pantoprazole disrupts protein degradation systems and sensitizes cancer cells to death under various stresses.

PubMed

Cao, Yu; Chen, Min; Tang, Dehua; Yan, Hongli; Ding, Xiwei; Zhou, Fan; Zhang, Mingming; Xu, Guifang; Zhang, Weijie; Zhang, Shu; Zhuge, Yuzheng; Wang, Lei; Zou, Xiaoping

2018-05-22

Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins. Notably, PPI-induced autophagy functioned as a downstream response of proteasome inhibition by PPI, while suppressing protein synthesis abrogated autophagy. Blocking autophagic flux in neutral pH condition or further impairing proteasome function with proteasome inhibitors, significantly aggravated PPI cytotoxicity by worsening protein degradation ability. Interestingly, under conditions of mitochondrial stress, PPI showed significant synergism when combined with Bcl-2 inhibitors. Taken together, these findings provide a new understanding of the impact of PPIs on cancer cells' biological processes and highlight the potential to develop more efficient and effective combination therapies.

Synthesis and application of polypyrrole/carrageenan nano-bio composite as a cathode catalyst in microbial fuel cells.

PubMed

Esmaeili, Chakavak; Ghasemi, Mostafa; Heng, Lee Yook; Hassan, Sedky H A; Abdi, Mahnaz M; Daud, Wan Ramli Wan; Ilbeygi, Hamid; Ismail, Ahmad Fauzi

2014-12-19

A novel nano-bio composite polypyrrole (PPy)/kappa-carrageenan(KC) was fabricated and characterized for application as a cathode catalyst in a microbial fuel cell (MFC). High resolution SEM and TEM verified the bud-like shape and uniform distribution of the PPy in the KC matrix. X-ray diffraction (XRD) has approved the amorphous structure of the PPy/KC as well. The PPy/KC nano-bio composites were then studied as an electrode material, due to their oxygen reduction reaction (ORR) ability as the cathode catalyst in the MFC and the results were compared with platinum (Pt) as the most common cathode catalyst. The produced power density of the PPy/KC was 72.1 mW/m(2) while it was 46.8 mW/m(2) and 28.8 mW/m(2) for KC and PPy individually. The efficiency of the PPy/KC electrode system is slightly lower than a Pt electrode (79.9 mW/m(2)) but due to the high cost of Pt electrodes, the PPy/KC electrode system has potential to be an alternative electrode system for MFCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation and characterization of RuO2/polypyrrole electrodes for supercapacitors

NASA Astrophysics Data System (ADS)

Li, Xiang; Wu, Yujiao; Zheng, Feng; Ling, Min; Lu, Fanghai

2014-11-01

Polypyrrole (PPy) embedded RuO2 electrodes were prepared by the composite method. Precursor solution of RuO2 was coated on tantalum sheet and annealed at 260 °C for 2.5 h to develop a thin film. PPy particles were deposited on RuO2 films and dried at 80 °C for 12 h to form composite electrode. Microstructure and morphology of RuO2/PPy electrode were characterized using Fourier transform infrared spectrometer, X-ray diffraction and scanning electron microscopy, respectively. Our results confirmed that counter ions are incorporated into RuO2 matrix. Structure of the composite with amorphous phase was verified by X-ray diffraction. Analysis by scanning electron microscopy reveals that during grain growth of RuO2/PPy, PPy particle size sharply increases as deposition time is over 20 min. Electrochemical properties of RuO2/PPy electrode were calculated using cyclic voltammetry. As deposition times of PPy are 10, 20, 25 and 30 min, specific capacitances of composite electrodes reach 657, 553, 471 and 396 F g-1, respectively. Cyclic behaviors of RuO2/PPy composite electrodes are stable.

A comparison of the psychometric properties of the psychopathic personality inventory full-length and short-form versions.

PubMed

Kastner, Rebecca M; Sellbom, Martin; Lilienfeld, Scott O

2012-03-01

The Psychopathic Personality Inventory (PPI) has shown promising construct validity as a measure of psychopathy. Because of its relative efficiency, a short-form version of the PPI (PPI-SF) was developed and has proven useful in many psychopathy studies. The validity of the PPI-SF, however, has not been thoroughly examined, and no studies have directly compared the validity of the short form with that of the full-length version. The current study was designed to compare the psychometric properties of both PPI versions, with an emphasis on convergent and discriminant validity in predicting external criteria conceptually relevant to psychopathy. We used both prison (n = 558) and college samples (n = 322) for this investigation. PPI scale scores were more reliable and more strongly correlated with the conceptually relevant criterion measures compared with the PPI-SF, particularly in the prison sample. There were no differences in relative discriminant validity. Thus, overall, the PPI full-length version showed more evidence of construct validity than did the short form, and the consequences of this psychometric difference should be considered when evaluating the clinical utility of each measure.

Modulators of 14-3-3 Protein–Protein Interactions

PubMed Central

2017-01-01

Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein–protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as “undruggable” targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products. PMID:28968506

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

PubMed Central

Bhattacharyya, Sanchari; Bershtein, Shimon; Yan, Jin; Argun, Tijda; Gilson, Amy I; Trauger, Sunia A; Shakhnovich, Eugene I

2016-01-01

Gene dosage toxicity (GDT) is an important factor that determines optimal levels of protein abundances, yet its molecular underpinnings remain unknown. Here, we demonstrate that overexpression of DHFR in E. coli causes a toxic metabolic imbalance triggered by interactions with several functionally related enzymes. Though deleterious in the overexpression regime, surprisingly, these interactions are beneficial at physiological concentrations, implying their functional significance in vivo. Moreover, we found that overexpression of orthologous DHFR proteins had minimal effect on all levels of cellular organization – molecular, systems, and phenotypic, in sharp contrast to E. coli DHFR. Dramatic difference of GDT between ‘E. coli’s self’ and ‘foreign’ proteins suggests the crucial role of evolutionary selection in shaping protein-protein interaction (PPI) networks at the whole proteome level. This study shows how protein overexpression perturbs a dynamic metabolon of weak yet potentially functional PPI, with consequences for the metabolic state of cells and their fitness. DOI: http://dx.doi.org/10.7554/eLife.20309.001 PMID:27938662

Polypyrrole nanostructures and their field emission investigations

NASA Astrophysics Data System (ADS)

Harpale, Kashmira; More, Mahendra A.; Koinkar, Pankaj M.; Patil, Sandip S.; Sonawane, Kishor M.

2015-03-01

Polypyrrole (PPy) nanostructures have been synthesized on indium doped tin oxide (ITO) substrates by a facile electrochemical route employing cyclic voltammetry (CV) mode. The morphology of the PPy thin films was observed to be influenced by the monomer concentration. Furthermore, FTIR revealed formation of electrically conducting state of PPy. Field emission investigations of the PPy nanostructures were carried out at base pressure of 1×10-8mbar. The values of turn-on field, corresponding to emission current density of 1 μA/cm2 were observed to be 0.6, 1.0 and 1.2 V/μm for the PPy films characterized with rod-like, cauliflower and granular morphology, respectively. In case of PPy nanorods maximum current density of 1.2 mA/cm2 has been drawn at electric field of 1 V/μm. The low turn on field, extraction of very high emission current density at relatively lower applied field and good emission stability propose the PPy nanorods as a promising material for field emission based devices.

Time-gated detection of protein-protein interactions with transcriptional readout

PubMed Central

Sanchez, Mateo I; Coukos, Robert; von Zastrow, Mark

2017-01-01

Transcriptional assays, such as yeast two-hybrid and TANGO, that convert transient protein-protein interactions (PPIs) into stable expression of transgenes are powerful tools for PPI discovery, screens, and analysis of cell populations. However, such assays often have high background and lose information about PPI dynamics. We have developed SPARK (Specific Protein Association tool giving transcriptional Readout with rapid Kinetics), in which proteolytic release of a membrane-tethered transcription factor (TF) requires both a PPI to deliver a protease proximal to its cleavage peptide and blue light to uncage the cleavage site. SPARK was used to detect 12 different PPIs in mammalian cells, with 5 min temporal resolution and signal ratios up to 37. By shifting the light window, we could reconstruct PPI time-courses. Combined with FACS, SPARK enabled 51 fold enrichment of PPI-positive over PPI-negative cells. Due to its high specificity and sensitivity, SPARK has the potential to advance PPI analysis and discovery. PMID:29189201

Factor structure and construct validity of the psychopathic personality inventory in a forensic sample.

PubMed

Gonsalves, Valerie M; McLawsen, Julia E; Huss, Matthew T; Scalora, Mario J

2013-01-01

A wealth of research has underscored the strong relationship between PCL-R scores and recidivism. However, mounting criticism cites the PCL-R's cumbersome administration procedures and failure to adequately measure core features associated with the construct of psychopathy (Skeem, Polaschek, Patrick, & Lilienfeld, 2011). In light of these concerns, this study examined the PPI and the PPI-R, which were designed to measure core personality features associated with psychopathy (Lilienfeld & Andrews, 1996; Lilienfeld & Widows, 2005). Study one examined the PPI relative to the PCL-R and examined its factor structure. The instruments shared few significant correlations and neither the PCL-R nor the PPI significantly predicted recidivism. Study two examined the PPI-R relative to the PCL-R, the PPI, both history of violence and future criminal activity and measure of related constructs. The PPI-R was significantly correlated with measures of empathy and criminal thinking and the factors were related to a history of violence and predicted future violent criminal behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis.

PubMed

Molina-Infante, Javier; van Rhijn, Bram D

2015-10-01

Gastro-oesophageal reflux disease (GORD) is the most common oesophageal disorder, whereas eosinophilic oesophagitis (EoE) is an emerging disease unresponsive to PPI therapy. Updated guidelines in 2011 described proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), a novel phenotype in EoE patients who were responsive to PPIs. This article aims to update the complex interplay between GORD, EoE and PPIs. Oesophageal mucosal integrity is diffusely impaired in EoE and PPI-REE patients. PPI-REE might occur with either normal or pathological pH monitoring. The genetic hallmark of EoE is overlapped in PPI-REE, but not in GORD. PPIs can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Acid hypersensitivity in EoE patients may explain symptomatic but not histological response on PPIs. Unsolved issues with PPI-REE are whether oesophageal barrier impairment is the cause or the effect of oesophageal eosinophilia and whether PPIs primarily targets barrier integrity or oesophageal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Involving the public in mental health and learning disability research: Can we, should we, do we?

PubMed

Paul, C; Holt, J

2017-10-01

WHAT IS KNOWN ON THE SUBJECT?: UK health policy is clear that researchers should involve the public throughout the research process. The public, including patients, carers and/or local citizens can bring a different and valuable perspective to the research process and improve the quality of research undertaken. Conducting health research is demanding with tight deadlines and scarce resources. This can make involving the public in research very challenging. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first time the attitudes of researchers working in mental health and learning disability services towards PPI have been investigated. The principles of service user involvement in mental health and learning disability services may support PPI in research as a tool of collaboration and empowerment. This article extends our understanding of the cultural and attitudinal barriers to implementing PPI guidelines in mental health and learning disability services. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Researchers in mental health and learning disability services need to champion, share and publish effective involvement work. Structural barriers to PPI work should be addressed locally and successful strategies shared nationally and internationally. Where PPI guidelines are being developed, attention needs to be paid to cultural factors in the research community to win "hearts and minds" and support the effective integration of PPI across the whole research process. Introduction Patient and public involvement (PPI) is integral to UK health research guidance; however, implementation is inconsistent. There is little research into the attitudes of NHS health researchers towards PPI. Aim This study explored the attitude of researchers working in mental health and learning disability services in the UK towards PPI in health research. Method Using a qualitative methodology, semi-structured interviews were conducted with a purposive sample of eight researchers. A framework approach was used in the analysis to generate themes and core concepts. Results Participants valued the perspective PPI could bring to research, but frustration with tokenistic approaches to involvement work was also evident. Some cultural and attitudinal barriers to integrating PPI across the whole research process were identified. Discussion Despite clear guidelines and established service user involvement, challenges still exist in the integration of PPI in mental health and learning disability research in the UK. Implications for practice Guidelines on PPI may not be enough to prompt changes in research practice. Leaders and researchers need to support attitudinal and cultural changes where required, to ensure the full potential of PPI in mental health and learning disability services research is realized. Relevance statement Findings suggest that despite clear guidelines and a history of service user involvement, there are still challenges to the integration of PPI in mental health and learning disability research in the UK. For countries where PPI guidelines are being developed, attention needs to be paid to cultural factors in the research community to win "hearts and minds" and support the effective integration of PPI across the whole research process. © 2017 John Wiley & Sons Ltd.

Demonstration of protein-fragment complementation assay using purified firefly luciferase fragments

PubMed Central

2013-01-01

Background Human interactome is predicted to contain 150,000 to 300,000 protein-protein interactions, (PPIs). Protein-fragment complementation assay (PCA) is one of the most widely used methods to detect PPI, as well as Förster resonance energy transfer (FRET). To date, successful applications of firefly luciferase (Fluc)-based PCA have been reported in vivo, in cultured cells and in cell-free lysate, owing to its high sensitivity, high signal-to-background (S/B) ratio, and reversible response. Here we show the assay also works with purified proteins with unexpectedly rapid kinetics. Results Split Fluc fragments both fused with a rapamycin-dependently interacting protein pair were made and expressed in E. coli system, and purified to homogeneity. When the proteins were used for PCA to detect rapamycin-dependent PPI, they enabled a rapid detection (~1 s) of PPI with high S/B ratio. When Fn7-8 domains (7 nm in length) that was shown to abrogate GFP mutant-based FRET was inserted between split Fluc and FKBP12 as a rigid linker, it still showed some response, suggesting less limitation in interacting partner’s size. Finally, the stability of the probe was investigated. Preincubation of the probes at 37 degreeC up to 1 h showed marked decrease of the luminescent signal to 1.5%, showing the limited stability of this system. Conclusion Fluc PCA using purified components will enable a rapid and handy detection of PPIs with high S/B ratio, avoiding the effects of concomitant components. Although the system might not be suitable for large-scale screening due to its limited stability, it can detect an interaction over larger distance than by FRET. This would be the first demonstration of Fluc PCA in vitro, which has a distinct advantage over other PPI assays. Our system enables detection of direct PPIs without risk of perturbation by PPI mediators in the complex cellular milieu. PMID:23536995

Neural networks for link prediction in realistic biomedical graphs: a multi-dimensional evaluation of graph embedding-based approaches.

PubMed

Crichton, Gamal; Guo, Yufan; Pyysalo, Sampo; Korhonen, Anna

2018-05-21

Link prediction in biomedical graphs has several important applications including predicting Drug-Target Interactions (DTI), Protein-Protein Interaction (PPI) prediction and Literature-Based Discovery (LBD). It can be done using a classifier to output the probability of link formation between nodes. Recently several works have used neural networks to create node representations which allow rich inputs to neural classifiers. Preliminary works were done on this and report promising results. However they did not use realistic settings like time-slicing, evaluate performances with comprehensive metrics or explain when or why neural network methods outperform. We investigated how inputs from four node representation algorithms affect performance of a neural link predictor on random- and time-sliced biomedical graphs of real-world sizes (∼ 6 million edges) containing information relevant to DTI, PPI and LBD. We compared the performance of the neural link predictor to those of established baselines and report performance across five metrics. In random- and time-sliced experiments when the neural network methods were able to learn good node representations and there was a negligible amount of disconnected nodes, those approaches outperformed the baselines. In the smallest graph (∼ 15,000 edges) and in larger graphs with approximately 14% disconnected nodes, baselines such as Common Neighbours proved a justifiable choice for link prediction. At low recall levels (∼ 0.3) the approaches were mostly equal, but at higher recall levels across all nodes and average performance at individual nodes, neural network approaches were superior. Analysis showed that neural network methods performed well on links between nodes with no previous common neighbours; potentially the most interesting links. Additionally, while neural network methods benefit from large amounts of data, they require considerable amounts of computational resources to utilise them. Our results indicate that when there is enough data for the neural network methods to use and there are a negligible amount of disconnected nodes, those approaches outperform the baselines. At low recall levels the approaches are mostly equal but at higher recall levels and average performance at individual nodes, neural network approaches are superior. Performance at nodes without common neighbours which indicate more unexpected and perhaps more useful links account for this.

A Comparison of the Psychometric Properties of the Psychopathic Personality Inventory Full-Length and Short-Form Versions

ERIC Educational Resources Information Center

Kastner, Rebecca M.; Sellbom, Martin; Lilienfeld, Scott O.

2012-01-01

The Psychopathic Personality Inventory (PPI) has shown promising construct validity as a measure of psychopathy. Because of its relative efficiency, a short-form version of the PPI (PPI-SF) was developed and has proven useful in many psychopathy studies. The validity of the PPI-SF, however, has not been thoroughly examined, and no studies have…

Willingness to pay to avoid health risks from road-traffic-related air pollution and noise across five countries.

PubMed

Istamto, Tifanny; Houthuijs, Danny; Lebret, Erik

2014-11-01

We conducted a multi-country study to estimate the perceived economic values of traffic-related air pollution and noise health risks within the framework of a large European project. We used contingent valuation as a method to assess the willingness-to-pay (WTP) for both types of pollutants simultaneously. We asked respondents how much they would be willing to pay annually to avoid certain health risks from specific pollutants. Three sets of vignettes with different levels of information were provided prior to the WTP questions. These vignettes described qualitative general health risks, a quantitative single health risk related to a pollutant, and a quantitative scenario of combined health risks related to a pollutant. The mean WTP estimates to avoid road-traffic air pollution effects for the three vignettes were: €130 per person per year (pp/y) for general health risks, €80 pp/y for a half year shorter in life expectancy, and €330 pp/y to a 50% decrease in road-traffic air pollution. Their medians were €40 pp/y, €10 pp/y and €50 pp/y, respectively. The mean WTP estimates to avoid road-traffic noise effects for the three vignettes were: €90 pp/y for general health risks, €100 pp/y for a 13% increase in severe annoyance, and €320 pp/y for a combined-risk scenario related to an increase of a noise level from 50 dB to 65 dB. Their medians were €20 pp/y, €20 pp/y and €50 pp/y, respectively. Risk perceptions and attitudes as well as environmental and pollutant concerns significantly affected WTP estimates. The observed differences in crude WTP estimates between countries changed considerably when perception-related variables were included in the WTP regression models. For this reason, great care should be taken when performing benefit transfer from studies in one country to another. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

PubMed

Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

2014-10-01

Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of the acid pocket. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Impact of Proton Pump Inhibitor Use on the Comparative Effectiveness and Safety of Prasugrel Versus Clopidogrel: Insights From the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study.

PubMed

Jackson, Larry R; Peterson, Eric D; McCoy, Lisa A; Ju, Christine; Zettler, Marjorie; Baker, Brian A; Messenger, John C; Faries, Douglas E; Effron, Mark B; Cohen, David J; Wang, Tracy Y

2016-10-21

Proton pump inhibitors (PPIs) reduce gastrointestinal bleeding events but may alter clopidogrel metabolism. We sought to understand the comparative effectiveness and safety of prasugrel versus clopidogrel in the context of proton pump inhibitor (PPI) use. Using data on 11 955 acute myocardial infarction (MI) patients treated with percutaneous coronary intervention at 233 hospitals and enrolled in the TRANSLATE-ACS study, we compared whether discharge PPI use altered the association of 1-year adjusted risks of major adverse cardiovascular events (MACE; death, MI, stroke, or unplanned revascularization) and Global Use of Strategies To Open Occluded Arteries (GUSTO) moderate/severe bleeding between prasugrel- and clopidogrel-treated patients. Overall, 17% of prasugrel-treated and 19% of clopidogrel-treated patients received a PPI at hospital discharge. At 1 year, patients discharged on a PPI versus no PPI had higher risks of MACE (adjusted hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.21-1.58) and GUSTO moderate/severe bleeding (adjusted HR 1.55, 95% CI 1.15-2.09). Risk of MACE was similar between prasugrel and clopidogrel regardless of PPI use (adjusted HR 0.88, 95% CI 0.62-1.26 with PPI, adjusted HR 1.07, 95% CI 0.90-1.28 without PPI, interaction P=0.31). Comparative bleeding risk associated with prasugrel versus clopidogrel use differed based on PPI use but did not reach statistical significance (adjusted HR 0.73, 95% CI 0.36-1.48 with PPI, adjusted HR 1.34, 95% CI 0.79-2.27 without PPI, interaction P=0.17). PPIs did not significantly affect the MACE and bleeding risk associated with prasugrel use, relative to clopidogrel. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503. © 2016 The Authors and Eli Lilly & Company. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Deficient prepulse inhibition in schizophrenia in a multi-site cohort: Internal replication and extension.

PubMed

Swerdlow, Neal R; Light, Gregory A; Thomas, Michael L; Sprock, Joyce; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2017-05-23

The Consortium on the Genetics of Schizophrenia (COGS) collected case-control endophenotype and genetic information from 2457 patients and healthy subjects (HS) across 5 test sites over 3.5 years. Analysis of the first "wave" (W1) of 1400 subjects identified prepulse inhibition (PPI) deficits in patients vs. HS. Data from the second COGS "wave" (W2), and the combined W(1+2), were used to assess: 1) the replicability of PPI deficits in this design; 2) the impact of response criteria on PPI deficits; and 3) PPI in a large cohort of antipsychotic-free patients. PPI in W2 HS (n=315) and schizophrenia patients (n=326) was compared to findings from W1; planned analyses assessed the impact of diagnosis, "wave" (1 vs. 2), and startle magnitude criteria. Combining waves allowed us to assess PPI in 120 antipsychotic-free patients, including many in the early course of illness. ANOVA of all W(1+2) subjects revealed robust PPI deficits in patients across "waves" (p<0.0004). Strict response criteria excluded almost 39% of all subjects, disproportionately impacting specific subgroups; ANOVA in this smaller cohort confirmed no significant effect of "wave" or "wave x diagnosis" interaction, and a significant effect of diagnosis (p<0.002). Antipsychotic-free, early-illness patients had particularly robust PPI deficits. Schizophrenia-linked PPI deficits were replicable across two multi-site "waves" of subjects collected over 3.5years. Strict response criteria disproportionately excluded older, male, non-Caucasian patients with low-normal hearing acuity. These findings set the stage for genetic analyses of PPI using the combined COGS wave 1 and 2 cohorts. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors.

PubMed

Graham, David Y; Opekun, Antone R; Hammoud, Fadi; Yamaoka, Yoshio; Reddy, Rita; Osato, Michael S; El-Zimaity, Hala M T

2003-05-01

The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results. In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration. Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects. PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats.

PubMed

de Oliveira, Rodolpho Pereira; Nagaishi, Karen Yuriko; Barbosa Silva, Regina Cláudia

2017-05-15

Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT) 2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10μg/0.3μl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4μg/0.3μl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants

PubMed Central

Yusop, Abdul Hakim Md; Daud, Nurizzati Mohd; Nur, Hadi; Kadir, Mohammed Rafiq Abdul; Hermawan, Hendra

2015-01-01

Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron. PMID:26057073

Coactivation of cognitive control networks during task switching.

PubMed

Yin, Shouhang; Deák, Gedeon; Chen, Antao

2018-01-01

The ability to flexibly switch between tasks is considered an important component of cognitive control that involves frontal and parietal cortical areas. The present study was designed to characterize network dynamics across multiple brain regions during task switching. Functional magnetic resonance images (fMRI) were captured during a standard rule-switching task to identify switching-related brain regions. Multiregional psychophysiological interaction (PPI) analysis was used to examine effective connectivity between these regions. During switching trials, behavioral performance declined and activation of a generic cognitive control network increased. Concurrently, task-related connectivity increased within and between cingulo-opercular and fronto-parietal cognitive control networks. Notably, the left inferior frontal junction (IFJ) was most consistently coactivated with the 2 cognitive control networks. Furthermore, switching-dependent effective connectivity was negatively correlated with behavioral switch costs. The strength of effective connectivity between left IFJ and other regions in the networks predicted individual differences in switch costs. Task switching was supported by coactivated connections within cognitive control networks, with left IFJ potentially acting as a key hub between the fronto-parietal and cingulo-opercular networks. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A novel non-contact radar sensor for affective and interactive analysis.

PubMed

Lin, Hong-Dun; Lee, Yen-Shien; Shih, Hsiang-Lan; Chuang, Bor-Nian

2013-01-01

Currently, many physiological signal sensing techniques have been applied for affective analysis in Human-Computer Interaction applications. Most known maturely developed sensing methods (EEG/ECG/EMG/Temperature/BP etc. al.) replied on contact way to obtain desired physiological information for further data analysis. However, those methods might cause some inconvenient and uncomfortable problems, and not easy to be used for affective analysis in interactive performing. To improve this issue, a novel technology based on low power radar technology (Nanosecond Pulse Near-field Sensing, NPNS) with 300 MHz radio-frequency was proposed to detect humans' pulse signal by the non-contact way for heartbeat signal extraction. In this paper, a modified nonlinear HRV calculated algorithm was also developed and applied on analyzing affective status using extracted Peak-to-Peak Interval (PPI) information from detected pulse signal. The proposed new affective analysis method is designed to continuously collect the humans' physiological signal, and validated in a preliminary experiment with sound, light and motion interactive performance. As a result, the mean bias between PPI (from NPNS) and RRI (from ECG) shows less than 1ms, and the correlation is over than 0.88, respectively.

Estimating Facets of Psychopathy From Normal Personality Traits: A Step Toward Community Epidemiological Investigations

PubMed Central

Benning, Stephen D.; Patrick, Christopher J.; Blonigen, Daniel M.; Hicks, Brian M.; Iacono, William G.

2008-01-01

In three samples consisting of community and undergraduate men and women and incarcerated men, we examined the criterion validity of two distinct factors of psychopathy embodied in the Psychopathic Personality Inventory (PPI) as indexed by primary trait scales from the Multidimensional Personality Questionnaire (MPQ). Consistent with the PPI factors themselves, MPQ-estimated PPI-I related negatively with internalizing disorder symptoms and fearfulness and positively with thrill and adventure seeking, sociability, activity, and narcissism. MPQ-estimated PPI-II was associated negatively with socialization and positively with externalizing disorder symptoms, impulsivity, disinhibition and boredom susceptibility, and trait anxiety and negative emotionality. Additionally, PPI-I was selectively related to the interpersonal facet of Factor 1 of the Psychopathy Checklist—Revised (PCL-R), whereas PPI-II was related preferentially to Factor 2 of the PCL-R. PMID:15695739

Significant enhancement in volumetric and gravimetric capacitance of Cu-TiO2/PPY composite for supercapacitor application

NASA Astrophysics Data System (ADS)

Purty, B.; Choudhary, R. B.

2018-04-01

Copper doped titanium dioxide-polypyrrole (Cu-TiO2/PPY) composite was successfully synthesized via chemical oxidative in-situ polymerization process. The structural and morphological properties of Cu-TiO2/PPY composite were investigated using X-ray diffractometer (XRD), field emission electron microscopy (FESEM) and transmission electron microscopy(TEM) techniques. The electrochemical properties of as-synthesized composite were studied using cyclic voltammetry (CV), galvanostatic charge discharge (GCD) and electrochemical impedance spectroscopic (EIS) techniques. The novel Cu-TiO2/PPY composite showed enhanced volumetric capacitance ˜714 F cm-1 and gravimetric capacitance ˜674 F g-1 at 1 A g-1. In addition an excellent coulombic efficiency and comparabley low charge transfer resistance than pure PPY suggests improved supercapacitive performance of Cu-TiO2/PPY composite as an electrode material.

Hydricity, electrochemistry, and excited-state chemistry of Ir complexes for CO 2 reduction

DOE PAGES

Manbeck, Gerald F.; Garg, Komal; Shimoda, Tomoe; ...

2016-12-01

Here, we prepared electron-rich derivatives of [Ir(tpy)(ppy)Cl] + with modification of the bidentate (ppy) or tridentate (tpy) ligands in attempt to increase the reactivity for CO 2 reduction and the ability to transfer hydrides (hydricity). Density functional theory (DFT) calculations reveal that complexes with dimethyl-substituted ppy have similar hydricities to the non-substituted parent complex, and photocatalytic CO 2 reduction studies show selective CO formation. Substitution of tpy for bis(benzimidazole)-phenyl or -pyridine (L3 and L4, respectively) induces changes in the physical properties much more pronounced than addition of methyl groups to ppy. Theoretical data predict [Ir(L3)(ppy)(H)] is the strongest hydride donormore » among complexes studied in this work, but [Ir(L3)(ppy)(NCCH 3)] + cannot be reduced photochemically because the excited state reduction potential is only 0.52 V due to the negative ground state potential of –1.91 V. The excited state [Ir(L4)(ppy)(NCCH 3)] 2+ is the strongest oxidant among complexes studied in this work and the singly reduced species is formed readily upon photolysis in the presence of tertiary amines. Both [Ir(L3)(ppy)(NCCH 3)] + and [Ir(L4)(ppy)(NCCH 3)] 2+ exhibit electrocatalytic current for CO 2 reduction. While a significantly greater overpotential is needed for the L3 complex, a small amount of formate (5-10 %) generation in addition to CO was observed as predicted by the DFT calculations.« less

[Evaluation of the prescription of proton pump inhibitors in persons aged 75years and older in a geriatric acute-care unit].

PubMed

Dipanda, Mélanie; Pioro, Laureline; Buttard, Maxime; d'Athis, Philippe; Asgassou, Sanaa; Putot, Sophie; Deïdda, Martha; Laborde, Caroline; Putot, Alain; Manckoundia, Patrick

2017-12-01

Proton pump inhibitors (PPI) are widely prescribed in France and could be responsible for adverse drug reactions especially in elderly persons (EP). In order to reduce the misuse of PPI and the excess cost to the Social Security Agency, the French health authorities (Haute Autorité de santé [HAS]) have published strict guidelines for their prescription. We conducted a study in EP to determine the proportion of PPI prescriptions outside HAS guidelines. This was a prospective, single-centre observational study in persons aged≥75 years admitted to a geriatric acute-care unit over a period of 6months. The prevalence of prescriptions for PPI and the proportion of prescriptions outside the guidelines were calculated. The sociodemographic and medical characteristics of EP treated with PPI were studied as were the reasons for the prescription of PPI. Among the 818 patients hospitalized during the study period, 270 were taking PPI on admission (33%). Among these prescriptions, 60% were outside the HAS guidelines. Gastro-oesophageal reflux was the leading indication for PPI (30%), followed by dyspepsia (19%). This study confirms the high prevalence of prescriptions for PPI and their misuse. As these drugs are apparently well tolerated, prescriptions are often renewed with no medical re-evaluation. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Involvement of serotoninergic 5-HT1A/2A, alpha-adrenergic and dopaminergic D1 receptors in St. John's wort-induced prepulse inhibition deficit: a possible role of hyperforin.

PubMed

Tadros, Mariane G; Mohamed, Mohamed R; Youssef, Amal M; Sabry, Gilane M; Sabry, Nagwa A; Khalifa, Amani E

2009-05-16

Prepulse inhibition (PPI) of acoustic startle response is a valuable paradigm for sensorimotor gating processes. Previous research showed that acute administration of St. John's wort extract (500 mg/kg, p.o.) to rats caused significant disruption of PPI while elevating monoamines levels in some brain areas. The cause-effect relationship between extract-induced PPI disruption and augmented monoaminergic transmission was studied using different serotoninergic, adrenergic and dopaminergic antagonists. The effects of hypericin and hyperforin, as the main active constituents of the extract, on PPI response were also tested. PPI disruption was prevented after blocking the serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors. Results also demonstrated a significant PPI deficit after acute treatment of rats with hyperforin, and not hypericin. In some conditions manifesting disrupted PPI response, apoptosis coexists. Electrophoresis of DNA isolated from brains of hyperforin-treated animals revealed absence of any abnormal DNA fragmentation patterns. It is concluded that serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors are involved in the disruptive effect of St. John's wort extract on PPI response in rats. We can also conclude that hyperforin, and not hypericin, is one of the active ingredients responsible for St. John's wort-induced PPI disruption with no relation to apoptotic processes.

Learning to work together - lessons from a reflective analysis of a research project on public involvement.

PubMed

Howe, A; Mathie, E; Munday, D; Cowe, M; Goodman, C; Keenan, J; Kendall, S; Poland, F; Staniszewska, S; Wilson, P

2017-01-01

Patient and public involvement (PPI) in research is very important, and funders and the NHS all expect this to happen. What this means in practice, and how to make it really successful, is therefore an important research question. This article analyses the experience of a research team using PPI, and makes recommendations on strengthening PPI in research. There were different PPI roles in our study - some people were part of the research team: some were on the advisory group; and there were patient groups who gave specific feedback on how to make research work better for their needs. We used minutes, other written documents, and structured individual and group reflections to learn from our own experiences over time. The main findings were:- for researchers and those in a PPI role to work in partnership, project structures must allow flexibility and responsiveness to different people's ideas and needs; a named link person can ensure support; PPI representatives need to feel fully included in the research; make clear what is expected for all roles; and ensure enough time and funding to allow meaningful involvement. Some roles brought more demands but also more rewards than others - highlighting that it is important that people giving up their time to help with research experience gains from doing so. Those contributing to PPI on a regular basis may want to learn new skills, rather than always doing the same things. Researchers and the public need to find ways to develop roles in PPI over time. We also found that, even for a team with expertise in PPI, there was a need both for understanding of different ways to contribute, and an evolving 'normalisation' of new ways of working together over time, which both enriched the process and the outputs. Background Patient and public involvement (PPI) is now an expectation of research funders, in the UK, but there is relatively little published literature on what this means in practice - nor is there much evaluative research about implementation and outputs. Policy literature endorses the need to include PPI representation at all stages of planning, performing and research dissemination, and recommends resource allocation to these roles; but details of how to make such inputs effective in practice are less common. While literature on power and participation informs the debate, there are relatively few published case studies of how this can play out through the lived experience of PPI in research; early findings highlight key issues around access to knowledge, resources, and interpersonal respect. This article describes the findings of a case study of PPI within a study about PPI in research. Methods The aim of the study was to look at how the PPI representatives' inputs had developed over time, key challenges and changes, and lessons learned. We used realist evaluation and normalisation process theory to frame and analyse the data, which was drawn from project documentation, minutes of meetings and workshops, field notes and observations made by PPI representatives and researchers; documented feedback after meetings and activities; and the structured feedback from two formal reflective meetings. Results Key findings included the need for named contacts who support, integrate and work with PPI contributors and researchers, to ensure partnership working is encouraged and supported to be as effective as possible. A structure for partnership working enabled this to be enacted systematically across all settings. Some individual tensions were nonetheless identified around different roles, with possible implications for clarifying expectations and deepening understandings of the different types of PPI contribution and of their importance. Even in a team with research expertise in PPI, the data showed that there were different phases and challenges to 'normalising' the PPI input to the project. Mutual commitment and flexibility, embedded through relationships across the team, led to inclusion and collaboration. Conclusion Work on developing relationships and teambuilding are as important for enabling partnership between PPI representatives and researchers as more practical components such as funding and information sharing. Early explicit exploration of the different roles and their contributions may assist effective participation and satisfaction.

Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China.

PubMed

Xiang, Yang-Lin; Zhang, Deng-Feng; Wang, Dong; Li, Yu-Ye; Yao, Yong-Gang

2015-11-01

Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. To investigate the potential involvement of OPA1 in leprosy. We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Theranostic nanoplatform based on polypyrrole nanoparticles for photoacoustic imaging and photothermal therapy

NASA Astrophysics Data System (ADS)

Liu, Hui; Li, Wenchao; Cao, Yang; Guo, Yuan; Kang, Yuejun

2018-03-01

Development of effective theranostic nanoplatforms against malignant tumor is still a challenge. With desirable near-infrared (NIR) light-responsive properties, polypyrrole nanoparticles (PPy NPs) are one of the promising theranostic candidates for cancer photoacoustic imaging and photothermal therapy. Here, PPy NPs with distinct sizes were prepared using a facile aqueous dispersion polymerization method. The formed PPy NPs are uniform in size with narrow size distribution. Characterization data show that PPy NPs with a diameter around 50 nm (P50) display stronger absorption in the NIR range compared to 40 and 60 nm PPy NPs, which further influences their photo-responsive properties. Due to their higher NIR absorption, P50 NPs have better photoacoustic imaging property and photothermal conversion ability than the other two kinds of PPy NPs. The photothermal stability of P50 NPs was proved to be excellent. The CCK-8 assays show that PPy NPs have obvious acute cytotoxicity within 6 h and desirable cytocompatibility for longer incubation time (12 and 24 h). After 6-h incubation, P50 NPs could be internalized by HeLa cells. Their photothermal tumor ablation effect was demonstrated under 808-nm laser irradiation. These findings may provide in-depth understanding of the PPy-based multifunctional nanomaterials for the development of theranostic systems against cancer.

Ligand anchored dendrimers based nanoconstructs for effective targeting to cancer cells.

PubMed

Gupta, Umesh; Dwivedi, Shailendra Kumar Dhar; Bid, Hemant Kumar; Konwar, Rituraj; Jain, N K

2010-06-30

Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer, AIDS, malaria etc. Cancer is a worldwide threat particularly in developing countries. A breakthrough research in this regard is a prime requirement. In the present study, folic acid was conjugated to fifth generation polypropylene imine (PPI) dendrimers and characterized through IR, NMR ((13)C and (1)H), ESI mass spectroscopy as well as electron microscopic studies. Doxorubicin (DOX), an effective anticancer drug, was used in the present study to develop and explore the anticancer potential of the dendrimer based formulations. DOX was loaded (approximately 26 and 65%) to the PPI dendrimers as well as folate conjugated PPI (PPI-FA) dendrimers, respectively. These ligand conjugated dendrimers displayed very less (approximately 3 and 4%, respectively, for PPI-FA and PPI-FA-DOX) hemolysis. The developed formulation PPI-FA-DOX was stable enough. In vitro drug release of the formulation was found to be faster in the acidic media than at the higher pH. The prepared formulation displayed a higher cell uptake in MCF-7 cancer cell lines as evidenced by fluorescence studies. The results suggested that, in future, folic acid conjugated PPI dendrimers may emerge as a better choice for anticancer drug targeting. 2010 Elsevier B.V. All rights reserved.

Effects of brain-derived and glial cell line-derived neurotrophic factors on startle response and disrupted prepulse inhibition in mice of DBA/2J inbred strain.

PubMed

Naumenko, Vladimir S; Bazovkina, Daria V; Morozova, Maryana V; Popova, Nina K

2013-08-29

Prepulse inhibition (PPI), the reduction in acoustic startle reflex when it is preceded by weak prepulse stimuli, is a measure of critical to normal brain functioning sensorimotor gating. PPI deficit was shown in a variety of psychiatric disorders including schizophrenia, and in DBA/2J mouse strain. In the current study, we examined the effects of brain-derived (BDNF) and glial cell line-derived (GDNF) neurotrophic factors on acoustic startle response and PPI in DBA/2J mice. It was found that BDNF (300 ng, i.c.v.) significantly increased amplitude of startle response and restored disrupted PPI in 7 days after acute administration. GDNF (800 ng, i.c.v.) did not produce significant alteration neither in amplitude of startle response nor in PPI in DBA/2J mice. The reversal effect of BDNF on PPI deficit was unusually long-lasting: significant increase in PPI was found 1.5 months after single acute BDNF administration. Long-term ameliorative effect BDNF on disrupted PPI suggested the implication of epigenetic mechanism in BDNF action on neurogenesis. BDNF rather than GDNF could be a perspective drug for the treatment of sensorimotor gating impairments. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors

PubMed Central

Farrell, Christopher; Morgan, Melissa; Tully, Owen; Wolov, Kevin; Kearney, Keith; Ngo, Benjamin; Mercogliano, Giancarlo; Thornton, James J; Valenzano, Mary Carmen; Mullin, James M

2012-01-01

AIM: To determine if the observed paracellular sucrose leak in Barrett’s esophagus patients is due to their proton pump inhibitor (PPI) use. METHODS: The in vivo sucrose permeability test was administered to healthy controls, to Barrett’s patients and to non-Barrett’s patients on continuous PPI therapy. Degree of leak was tested for correlation with presence of Barrett’s, use of PPIs, and length of Barrett’s segment and duration of PPI use. RESULTS: Barrett’s patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was observed in Barrett’s patients who ceased PPI use for 7 d. Although initial introduction of PPI use (in a PPI-naïve population) results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spontaneous decline in leak. The sucrose leak observed in Barrett’s patients showed no correlation to the amount of Barrett’s tissue present in the esophagus. CONCLUSION: Although future research is needed to determine the degree of paracellular leak in actual Barrett’s mucosa, the relatively high degree of leak observed with in vivo sucrose permeability measurement of Barrett’s patients reflects their PPI use and not their Barrett’s tissue per se. PMID:22719187

Examining the necessity for and utility of the Psychopathic Personality Inventory-Revised (PPI-R) validity scales.

PubMed

Anderson, Jaime L; Sellbom, Martin; Wygant, Dustin B; Edens, John F

2013-10-01

The present study aimed to investigate the need for and utility of the Psychopathic Personality Inventory-Revised (PPI-R) Deviant Responding (DR) and Virtuous Responding (VR) validity scales in identifying overreporting and underreporting, respectively. Since the PPI-R was published, there has not been an independent peer-reviewed examination of these scales. Participants were 384 undergraduate individuals asked to respond to the PPI-R under standard, underreporting, or overreporting instructions. A comparison group consisting of 200 forensic psychiatric patients was also used for the overreporting analyses. Effects of response bias on mean elevations on the PPI-R substantive scales were examined along with the effects on the PPI-R total, factor, and content scales' correlations with other relevant extratest measures of psychopathy. Mean elevations differed significantly, and correlations with extratest measures of psychopathy were significantly lower. Substantial decrement in psychometric validity of PPI-R scores was observed in the simulation conditions. In addition, the utility of the PPI-R validity scales in differentiating between groups was also determined. Both the VR and DR scales showed utility in differentiating between their respective dissimulation condition and the comparison groups, with acceptable rates of sensitivity and specificity. PsycINFO Database Record (c) 2013 APA, all rights reserved

Prediction of protein-protein interactions from amino acid sequences with ensemble extreme learning machines and principal component analysis

PubMed Central

2013-01-01

Background Protein-protein interactions (PPIs) play crucial roles in the execution of various cellular processes and form the basis of biological mechanisms. Although large amount of PPIs data for different species has been generated by high-throughput experimental techniques, current PPI pairs obtained with experimental methods cover only a fraction of the complete PPI networks, and further, the experimental methods for identifying PPIs are both time-consuming and expensive. Hence, it is urgent and challenging to develop automated computational methods to efficiently and accurately predict PPIs. Results We present here a novel hierarchical PCA-EELM (principal component analysis-ensemble extreme learning machine) model to predict protein-protein interactions only using the information of protein sequences. In the proposed method, 11188 protein pairs retrieved from the DIP database were encoded into feature vectors by using four kinds of protein sequences information. Focusing on dimension reduction, an effective feature extraction method PCA was then employed to construct the most discriminative new feature set. Finally, multiple extreme learning machines were trained and then aggregated into a consensus classifier by majority voting. The ensembling of extreme learning machine removes the dependence of results on initial random weights and improves the prediction performance. Conclusions When performed on the PPI data of Saccharomyces cerevisiae, the proposed method achieved 87.00% prediction accuracy with 86.15% sensitivity at the precision of 87.59%. Extensive experiments are performed to compare our method with state-of-the-art techniques Support Vector Machine (SVM). Experimental results demonstrate that proposed PCA-EELM outperforms the SVM method by 5-fold cross-validation. Besides, PCA-EELM performs faster than PCA-SVM based method. Consequently, the proposed approach can be considered as a new promising and powerful tools for predicting PPI with excellent performance and less time. PMID:23815620

Global De Novo Protein-Protein Interactome Elucidates Interactions of Drought-Responsive Proteins in Horse Gram (Macrotyloma uniflorum).

PubMed

Bhardwaj, Jyoti; Gangwar, Indu; Panzade, Ganesh; Shankar, Ravi; Yadav, Sudesh Kumar

2016-06-03

Inspired by the availability of de novo transcriptome of horse gram (Macrotyloma uniflorum) and recent developments in systems biology studies, the first ever global protein-protein interactome (PPI) map was constructed for this highly drought-tolerant legume. Large-scale studies of PPIs and the constructed database would provide rationale behind the interplay at cascading translational levels for drought stress-adaptive mechanisms in horse gram. Using a bidirectional approach (interolog and domain-based), a high-confidence interactome map and database for horse gram was constructed. Available transcriptomic information for shoot and root tissues of a sensitive (M-191; genotype 1) and a drought-tolerant (M-249; genotype 2) genotype of horse gram was utilized to draw comparative PPI subnetworks under drought stress. High-confidence 6804 interactions were predicted among 1812 proteins covering about one-fourth of the horse gram proteome. The highest number of interactions (33.86%) in horse gram interactome matched with Arabidopsis PPI data. The top five hub nodes mostly included ubiquitin and heat-shock-related proteins. Higher numbers of PPIs were found to be responsive in shoot tissue (416) and root tissue (2228) of genotype 2 compared with shoot tissue (136) and root tissue (579) of genotype 1. Characterization of PPIs using gene ontology analysis revealed that kinase and transferase activities involved in signal transduction, cellular processes, nucleocytoplasmic transport, protein ubiquitination, and localization of molecules were most responsive to drought stress. Hence, these could be framed in stress adaptive mechanisms of horse gram. Being the first legume global PPI map, it would provide new insights into gene and protein regulatory networks for drought stress tolerance mechanisms in horse gram. Information compiled in the form of database (MauPIR) will provide the much needed high-confidence systems biology information for horse gram genes, proteins, and involved processes. This information would ease the effort and increase the efficacy for similar studies on other legumes. Public access is available at http://14.139.59.221/MauPIR/ .

Controlling the polypyrrole microstructures using swollen liquid crystals as structure directing agent

NASA Astrophysics Data System (ADS)

Dutt, S.; Sharma, R.

2017-10-01

Microstructures of polypyrrole (PPy) with different morphology were synthesized using swollen liquid crystals (SLCs) as soft structure directing agents and confinement effect on the control of PPy microstructures have been thoroughly investigated. SLCs are the quaternary mixtures of aqueous phase: oil phase: surfactant: co-surfactant. Mesophases of PPy were synthesized by trapping small amount of pyrrole in the oil phase of SLCs. Spherical, fiber and rod-like microstructures of PPy were synthesized by adding ammonium persulphate (APS) as an oxidant under different synthesis conditions using SLCs. The possible mechanism for the formation of different PPy microstructures also proposed in this study.

Ovarian Cancer Differential Interactome and Network Entropy Analysis Reveal New Candidate Biomarkers.

PubMed

Ayyildiz, Dilara; Gov, Esra; Sinha, Raghu; Arga, Kazim Yalcin

2017-05-01

Ovarian cancer is one of the most common cancers and has a high mortality rate due to insidious symptoms and lack of robust diagnostics. A hitherto understudied concept in cancer pathogenesis may offer new avenues for innovation in ovarian cancer biomarker development. Cancer cells are characterized by an increase in network entropy, and several studies have exploited this concept to identify disease-associated gene and protein modules. We report in this study the changes in protein-protein interactions (PPIs) in ovarian cancer within a differential network (interactome) analysis framework utilizing the entropy concept and gene expression data. A compendium of six transcriptome datasets that included 140 samples from laser microdissected epithelial cells of ovarian cancer patients and 51 samples from healthy population was obtained from Gene Expression Omnibus, and the high confidence human protein interactome (31,465 interactions among 10,681 proteins) was used. The uncertainties of the up- or downregulation of PPIs in ovarian cancer were estimated through an entropy formulation utilizing combined expression levels of genes, and the interacting protein pairs with minimum uncertainty were identified. We identified 105 proteins with differential PPI patterns scattered in 11 modules, each indicating significantly affected biological pathways in ovarian cancer such as DNA repair, cell proliferation-related mechanisms, nucleoplasmic translocation of estrogen receptor, extracellular matrix degradation, and inflammation response. In conclusion, we suggest several PPIs as biomarker candidates for ovarian cancer and discuss their future biological implications as potential molecular targets for pharmaceutical development as well. In addition, network entropy analysis is a concept that deserves greater research attention for diagnostic innovation in oncology and tumor pathogenesis.

L-lactic acid and sodium p-toluenesulfonate co-doped polypyrrole for high performance cathode in sodium ion battery

NASA Astrophysics Data System (ADS)

Liao, Qishu; Hou, Hongying; Liu, Xianxi; Yao, Yuan; Dai, Zhipeng; Yu, Chengyi; Li, Dongdong

2018-04-01

In this work, polypyrrole (PPy) was co-doped with L-lactic acid (LA) and sodium p-toluenesulfonate (TsONa) for high performance cathode in sodium ion battery (SIB) via facile one-step electropolymerization on Fe foil. The as-synthesized LA/TsONa co-doped PPy cathode was investigated in terms of scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), galvanostatic charge/discharge and cyclic voltammetry (CV). The results suggested that some oval-bud-like LA/TsONa co-doped PPy particles did form and tightly combine with the surface of Fe foil; furthermore, LA/TsONa co-doped PPy cathode also delivered higher electrochemical performances than TsONa mono-doped PPy cathode. For example, the initial specific discharge capacity was as high as about 124 mAh/g, and the reversible specific capacity still maintained at about 110 mAh/g even after 50 cycles, higher than those of TsONa mono-doped PPy cathode. The synergy effect of multi components of LA/TsONa co-doped PPy cathode should be responsible for high electrochemical performances.

Further Characterization of the Predictive Validity of the Brattleboro Rat Model for Antipsychotic Efficacy

PubMed Central

Feifel, D.; Shilling, P. D.; Melendez, G.

2014-01-01

Our laboratory and others have reported that Brattleboro (BRAT) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in prepulse inhibition (PPI) homologous to those observed in schizophrenia patients and that these deficits are reversed by antipsychotic drugs (APDs). To further evaluate the potential predictive validity of BRAT rat PPI for APDs, we compared the effects of acute subcutaneous administration of the typical APD chlorpromazine to that of three psychotropic drugs without antipsychotic efficacy, the antidepressant imipramine, the anxiolytic diazepam and the anticonvulsant mood stabilizer valproic acid on male and female BRAT rat PPI. Male and female BRAT rats exhibited baseline (saline treatment) PPI that was not different from each other (21.1 % and 21.3 %, respectively) and low compared to those historically exhibited by LE rats (approximately 59 %). Chlorpromazine facilitated PPI in male and female BRAT rats, whereas imipramine, diazepam, and valproic acid had no significant effect on PPI. These results suggest that PPI in the BRAT rat responds specifically to drugs with APD efficacy but not psychotropic drugs of different therapeutic families. PMID:21106605

Tungsten oxide@polypyrrole core-shell nanowire arrays as novel negative electrodes for asymmetric supercapacitors.

PubMed

Wang, Fengmei; Zhan, Xueying; Cheng, Zhongzhou; Wang, Zhenxing; Wang, Qisheng; Xu, Kai; Safdar, Muhammad; He, Jun

2015-02-11

Among active pseudocapacitive materials, polypyrrole (PPy) is a promising electrode material in electrochemical capacitors. PPy-based materials research has thus far focused on its electrochemical performance as a positive electrode rather than as a negative electrode for asymmetric supercapacitors (ASCs). Here high-performance electrochemical supercapacitors are designed with tungsten oxide@PPy (WO3 @PPy) core-shell nanowire arrays and Co(OH)2 nanowires grown on carbon fibers. The WO3 @PPy core-shell nanowire electrode exhibits a high capacitance (253 mF/cm2) in negative potentials (-1.0-0.0 V). The ASCs packaged with CF-Co(OH)2 as a positive electrode and CF-WO3 @PPy as a negative electrode display a high volumetric capacitance up to 2.865 F/cm3 based on volume of the device, an energy density of 1.02 mWh/cm3 , and very good stability performance. These findings promote the application of PPy-based nanostructures as advanced negative electrodes for ASCs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facile synthesis of polypyrrole functionalized nickel foam with catalytic activity comparable to Pt for the poly-generation of hydrogen and electricity

NASA Astrophysics Data System (ADS)

Tang, Tiantian; Li, Kan; Shen, Zhemin; Sun, Tonghua; Wang, Yalin; Jia, Jinping

2016-01-01

Polypyrrole functionalized nickel foam is facilely prepared through the potentiostatic electrodeposition. The PPy-functionalized Ni foam functions as a hydrogen-evolution cathode in a rotating disk photocatalytic fuel cell, in which hydrogen energy and electric power are generated by consuming organic wastes. The PPy-functionalized Ni foam cathode exhibits stable catalytic activities after thirteen continuous runs. Compared with net or plate structure, the Ni foam with a unique three-dimensional reticulate structure is conducive to the electrodeposition of PPy. Compared with Pt-group electrode, PPy-coated Ni foam shows a satisfactory catalytic performance for the H2 evolution. The combination of PPy and Ni forms a synergistic effect for the rapid trapping and removal of proton from solution and the catalytic reduction of proton to hydrogen. The PPy-functionalized Ni foam could be applied in photocatalytic and photoelectrochemical generation of H2. In all, we report a low cost, high efficient and earth abundant PPy-functionalized Ni foam with a satisfactory catalytic activities comparable to Pt for the practical application of poly-generation of hydrogen and electricity.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

MEGADOCK: An All-to-All Protein-Protein Interaction Prediction System Using Tertiary Structure Data

PubMed Central

Ohue, Masahito; Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ishida, Takashi; Akiyama, Yutaka

2014-01-01

The elucidation of protein-protein interaction (PPI) networks is important for understanding cellular structure and function and structure-based drug design. However, the development of an effective method to conduct exhaustive PPI screening represents a computational challenge. We have been investigating a protein docking approach based on shape complementarity and physicochemical properties. We describe here the development of the protein-protein docking software package “MEGADOCK” that samples an extremely large number of protein dockings at high speed. MEGADOCK reduces the calculation time required for docking by using several techniques such as a novel scoring function called the real Pairwise Shape Complementarity (rPSC) score. We showed that MEGADOCK is capable of exhaustive PPI screening by completing docking calculations 7.5 times faster than the conventional docking software, ZDOCK, while maintaining an acceptable level of accuracy. When MEGADOCK was applied to a subset of a general benchmark dataset to predict 120 relevant interacting pairs from 120 x 120 = 14,400 combinations of proteins, an F-measure value of 0.231 was obtained. Further, we showed that MEGADOCK can be applied to a large-scale protein-protein interaction-screening problem with accuracy better than random. When our approach is combined with parallel high-performance computing systems, it is now feasible to search and analyze protein-protein interactions while taking into account three-dimensional structures at the interactome scale. MEGADOCK is freely available at http://www.bi.cs.titech.ac.jp/megadock. PMID:23855673