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Sample records for extracts functionally modulate

  1. Zingiber officinale Roscoe aqueous extract modulates ...

    African Journals Online (AJOL)

    Zingiber officinale Roscoe aqueous extract modulates Matrixmetalloproteinases and tissue inhibitors of Metalloproteinases expressions in Dengue virus-infected cells: implications for prevention of vascular permeability.

  2. Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells.

    Science.gov (United States)

    Kwon, Ho-Keun; Jeon, Won Kyung; Hwang, Ji-Sun; Lee, Choong-Gu; So, Jae-Seon; Park, Jin-A; Ko, Byoung Seob; Im, Sin-Hyeog

    2009-06-18

    Cinnamon is one of the most widely used herbal medicines with diverse bioactive effects. However, little evidence has been reported about the potential anti-tumor effects of cinnamon. In vitro and in vivo system, cinnamon treatment strongly inhibited the expression of pro-angiogenic factors and master regulators of tumor progression not only in melanoma cell lines but also in experimental melanoma model. In addition, cinnamon treatment increased the anti-tumor activities of CD8(+) T cells by increasing the levels of cytolytic molecules and their cytotoxic activity. In conclusion, cinnamon extract has the potential to be an alternative medicine for tumor treatment.

  3. An effective method for network module extraction from microarray data

    Directory of Open Access Journals (Sweden)

    Mahanta Priyakshi

    2012-08-01

    Full Text Available Abstract Background The development of high-throughput Microarray technologies has provided various opportunities to systematically characterize diverse types of computational biological networks. Co-expression network have become popular in the analysis of microarray data, such as for detecting functional gene modules. Results This paper presents a method to build a co-expression network (CEN and to detect network modules from the built network. We use an effective gene expression similarity measure called NMRS (Normalized mean residue similarity to construct the CEN. We have tested our method on five publicly available benchmark microarray datasets. The network modules extracted by our algorithm have been biologically validated in terms of Q value and p value. Conclusions Our results show that the technique is capable of detecting biologically significant network modules from the co-expression network. Biologist can use this technique to find groups of genes with similar functionality based on their expression information.

  4. Histamine modulates microglia function

    Science.gov (United States)

    2012-01-01

    Background Histamine is commonly acknowledged as an inflammatory mediator in peripheral tissues, leaving its role in brain immune responses scarcely studied. Therefore, our aim was to uncover the cellular and molecular mechanisms elicited by this molecule and its receptors in microglia-induced inflammation by evaluating cell migration and inflammatory mediator release. Methods Firstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR analysis, immunocytochemistry and Western blotting. Then, we evaluated the role of histamine in microglial cell motility by performing scratch wound assays. Results were further confirmed using murine cortex explants. Finally, interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by ELISA measurements to determine the role of histamine on the release of these inflammatory mediators. Results After 12 h of treatment, 100 μM histamine and 10 μg/ml histamine-loaded poly (lactic-co-glycolic acid) microparticles significantly stimulated microglia motility via H4R activation. In addition, migration involves α5β1 integrins, and p38 and Akt signaling pathways. Migration of microglial cells was also enhanced in the presence of lipopolysaccharide (LPS, 100 ng/ml), used as a positive control. Importantly, histamine inhibited LPS-stimulated migration via H4R activation. Histamine or H4R agonist also inhibited LPS-induced IL-1β release in both N9 microglia cell line and hippocampal organotypic slice cultures. Conclusions To our knowledge, we are the first to show a dual role of histamine in the modulation of microglial inflammatory responses. Altogether, our data suggest that histamine per se triggers microglia motility, whereas histamine impedes LPS-induced microglia migration and IL-1β release. This last datum assigns a new putative anti-inflammatory role for

  5. Extraction of temperature dependent interfacial resistance of thermoelectric modules

    DEFF Research Database (Denmark)

    Chen, Min

    2011-01-01

    This article discusses an approach for extracting the temperature dependency of the electrical interfacial resistance associated with thermoelectric devices. The method combines a traditional module-level test rig and a nonlinear numerical model of thermoelectricity to minimize measurement errors...... on the interfacial resistance. The extracted results represent useful data to investigating the characteristics of thermoelectric module resistance and comparing performance of various modules....

  6. GABA(A) receptor modulation by terpenoids from Sideritis extracts.

    Science.gov (United States)

    Kessler, Artur; Sahin-Nadeem, Hilal; Lummis, Sarah C R; Weigel, Ingrid; Pischetsrieder, Monika; Buettner, Andrea; Villmann, Carmen

    2014-04-01

    GABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation. Single volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABAA receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As Sideritis extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABAA receptors, a high-throughput method was used for identification of the most effective terpenoid substances on GABA-affinity of α1β2γ2 receptors expressed in transfected cell lines. Isopulegol, pinocarveol, verbenol, and myrtenol were the most potent modifiers of GABAA receptor function. Comparing the chemical structures, the action of terpenes on GABAA receptors is most probably due to the presence of hydroxyl groups and a bicyclic character of the substances tested. We propose an allosteric modulation independent from the γ2 subunit and similar to the action of alcohols and anesthetics. © 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim.

  7. GABAA receptor modulation by terpenoids from Sideritis extracts

    Science.gov (United States)

    Kessler, Artur; Sahin-Nadeem, Hilal; Lummis, Sarah C R; Weigel, Ingrid; Pischetsrieder, Monika; Buettner, Andrea; Villmann, Carmen

    2014-01-01

    Scope GABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation. Methods and results Single volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABAA receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As Sideritis extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABAA receptors, a high-throughput method was used for identification of the most effective terpenoid substances on GABA-affinity of α1β2γ2 receptors expressed in transfected cell lines. Isopulegol, pinocarveol, verbenol, and myrtenol were the most potent modifiers of GABAA receptor function. Conclusion Comparing the chemical structures, the action of terpenes on GABAA receptors is most probably due to the presence of hydroxyl groups and a bicyclic character of the substances tested. We propose an allosteric modulation independent from the γ2 subunit and similar to the action of alcohols and anesthetics. PMID:24273211

  8. PyEEG: an open source Python module for EEG/MEG feature extraction.

    Science.gov (United States)

    Bao, Forrest Sheng; Liu, Xin; Zhang, Christina

    2011-01-01

    Computer-aided diagnosis of neural diseases from EEG signals (or other physiological signals that can be treated as time series, e.g., MEG) is an emerging field that has gained much attention in past years. Extracting features is a key component in the analysis of EEG signals. In our previous works, we have implemented many EEG feature extraction functions in the Python programming language. As Python is gaining more ground in scientific computing, an open source Python module for extracting EEG features has the potential to save much time for computational neuroscientists. In this paper, we introduce PyEEG, an open source Python module for EEG feature extraction.

  9. Extracting expression modules from perturbational gene expression compendia

    Directory of Open Access Journals (Sweden)

    Van Dijck Patrick

    2008-04-01

    Full Text Available Abstract Background Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems biology perspective. However, the perturbational nature of such data imposes specific challenges on the computational methods used to analyze them. In particular, traditional clustering algorithms have difficulties in handling one of the prominent features of perturbational compendia, namely partial coexpression relationships between genes. Biclustering methods on the other hand are specifically designed to capture such partial coexpression patterns, but they show a variety of other drawbacks. For instance, some biclustering methods are less suited to identify overlapping biclusters, while others generate highly redundant biclusters. Also, none of the existing biclustering tools takes advantage of the staple of perturbational expression data analysis: the identification of differentially expressed genes. Results We introduce a novel method, called ENIGMA, that addresses some of these issues. ENIGMA leverages differential expression analysis results to extract expression modules from perturbational gene expression data. The core parameters of the ENIGMA clustering procedure are automatically optimized to reduce the redundancy between modules. In contrast to the biclusters produced by most other methods, ENIGMA modules may show internal substructure, i.e. subsets of genes with distinct but significantly related expression patterns. The grouping of these (often functionally related patterns in one module greatly aids in the biological interpretation of the data. We show that ENIGMA outperforms other methods on artificial datasets, using a quality criterion that, unlike other criteria, can be used for algorithms that generate overlapping clusters and that can be modified to take redundancy between clusters into account. Finally, we apply ENIGMA to the Rosetta compendium of expression profiles for

  10. Modulation transfer function measurement using nonspecific views

    Science.gov (United States)

    Delvit, Jean-Marc; Leger, Dominique; Roques, Sylvie; Valorge, Christophe

    2003-03-01

    The measurement of the Modulation Transfer Function (MTF) to quantify the quality of an imaging system proves to be very important in the context of Earth observation satellites. In particular, this measurement is essential to carry out the focusing of the telescope, or to implement a deconvolution filter whose goal is to enhance the image contrast or to reduce the noise. Its knowledge also allows us to compare the characteristics of different known and unknown satellites. In this paper, we suggest an univariant MTF measurement method using non specific views. First of all, the landscape has to be characterized in order to discriminate ground structure information from MTF information. Once this separation is carried out, landscape structure information can be extracted, allowing a classification between very uniform scenes and more structured ones. Then the MTF, which is described by a bidimensional analytical physical model, can be assessed using an artificial neural network. The principle is to use the artificial neural network to learn the MTF of simulated or perfectly known images, and then to use it to assess the MTF of totally unknown images. One can show that this method is robust even if the noise is taken into account. As a result, maximum MTF assessment errors are less than 10%. This enables us to suggest further developments including a general scheme of criteria assessment of image quality.

  11. FUMET: A fuzzy network module extraction technique for gene ...

    Indian Academy of Sciences (India)

    FUMET: A fuzzy network module extraction technique for gene expression data. Priyakshi Mahanta Hasin Afzal Ahmed ... Bhattacharyya1 Ashish Ghosh2. Department of Computer Science and Engineering, Tezpur University, Napaam 784 028, India; Machine Intelligent Unit, Indian Statistical Institute, Kolkata 700 108, India ...

  12. Neuroimmune modulation of gut function

    Science.gov (United States)

    There is considerable interest in the mechanisms and pathways involved in the neuro-immune regulation of gut function. The number of cell types and possible interactions is staggering and there are a number of recent reviews detailing various aspects of these interactions, many of which focus on ...

  13. Caffeine Modulates Attention Network Function

    Science.gov (United States)

    Brunye, Tad T.; Mahoney, Caroline R.; Lieberman, Harris R.; Taylor, Holly A.

    2010-01-01

    The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a flanker task designed to test Posner's three visual attention network functions: alerting, orienting, and executive control [Posner, M. I. (2004). "Cognitive neuroscience of attention". New York, NY: Guilford Press]. In a placebo-controlled, double-blind…

  14. PyEEG: An Open Source Python Module for EEG/MEG Feature Extraction

    Directory of Open Access Journals (Sweden)

    Forrest Sheng Bao

    2011-01-01

    Full Text Available Computer-aided diagnosis of neural diseases from EEG signals (or other physiological signals that can be treated as time series, e.g., MEG is an emerging field that has gained much attention in past years. Extracting features is a key component in the analysis of EEG signals. In our previous works, we have implemented many EEG feature extraction functions in the Python programming language. As Python is gaining more ground in scientific computing, an open source Python module for extracting EEG features has the potential to save much time for computational neuroscientists. In this paper, we introduce PyEEG, an open source Python module for EEG feature extraction.

  15. Optimized Feature Extraction for Temperature-Modulated Gas Sensors

    Directory of Open Access Journals (Sweden)

    Alexander Vergara

    2009-01-01

    Full Text Available One of the most serious limitations to the practical utilization of solid-state gas sensors is the drift of their signal. Even if drift is rooted in the chemical and physical processes occurring in the sensor, improved signal processing is generally considered as a methodology to increase sensors stability. Several studies evidenced the augmented stability of time variable signals elicited by the modulation of either the gas concentration or the operating temperature. Furthermore, when time-variable signals are used, the extraction of features can be accomplished in shorter time with respect to the time necessary to calculate the usual features defined in steady-state conditions. In this paper, we discuss the stability properties of distinct dynamic features using an array of metal oxide semiconductors gas sensors whose working temperature is modulated with optimized multisinusoidal signals. Experiments were aimed at measuring the dispersion of sensors features in repeated sequences of a limited number of experimental conditions. Results evidenced that the features extracted during the temperature modulation reduce the multidimensional data dispersion among repeated measurements. In particular, the Energy Signal Vector provided an almost constant classification rate along the time with respect to the temperature modulation.

  16. Audio feature extraction using probability distribution function

    Science.gov (United States)

    Suhaib, A.; Wan, Khairunizam; Aziz, Azri A.; Hazry, D.; Razlan, Zuradzman M.; Shahriman A., B.

    2015-05-01

    Voice recognition has been one of the popular applications in robotic field. It is also known to be recently used for biometric and multimedia information retrieval system. This technology is attained from successive research on audio feature extraction analysis. Probability Distribution Function (PDF) is a statistical method which is usually used as one of the processes in complex feature extraction methods such as GMM and PCA. In this paper, a new method for audio feature extraction is proposed which is by using only PDF as a feature extraction method itself for speech analysis purpose. Certain pre-processing techniques are performed in prior to the proposed feature extraction method. Subsequently, the PDF result values for each frame of sampled voice signals obtained from certain numbers of individuals are plotted. From the experimental results obtained, it can be seen visually from the plotted data that each individuals' voice has comparable PDF values and shapes.

  17. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  18. Hypericum perforatum extract modulates cortical plasticity in humans.

    Science.gov (United States)

    Concerto, Carmen; Boo, Hyunji; Hu, Charles; Sandilya, Priam; Krish, Anita; Chusid, Eileen; Coira, Diego; Aguglia, Eugenio; Battaglia, Fortunato

    2018-01-01

    Hypericum perforatum (HYP) extract is one of the most commonly used complementary alternative medicines (CAMs) for the treatment of mild-to-moderate depression. Non-invasive brain stimulation protocols can be used to investigate the effect of psychoactive substances on the human brain. In this study, we explored the effect of a single dose of HYP extract (WS 5570) intake on corticospinal excitability and plasticity in humans. Twenty-eight healthy subjects were required to intake 900 mg of either HYP extract or placebo. Cortical excitability was assessed using single and paired transcranial magnetic stimulation (TMS). The electrophysiological parameters of motor threshold, recruitment of motor-evoked potentials (MEPs), cortical silent period (CSP), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were tested before and 2 and 5 h after the oral intake. Spinal and neuromuscular excitability and peripheral nerve excitability were measured by F response and M-wave. Cortical plasticity was induced using transcranial direct current stimulation (tDCS). Subjects received either HYP extract or placebo before anodal and cathodal tDCS of the primary motor cortex. Plasticity was assessed by MEP amplitudes. HYP extract reversed cathodal tDCS-induced long-term depression (LTD)-like plasticity into facilitation, as compared to placebo. HYP extract did not have a significant effect on anodal tDCS-induced plasticity and TMS measures of motor cortex and spinal/neuromuscular excitability. Our findings suggest that a single oral dose of HYP extract modulates cortical plasticity in healthy subjects and provide new insight into its possible mechanism of action in humans.

  19. Declarative Debugging of Maude Functional Modules

    OpenAIRE

    Caballero, Rafael; Martí Oliet, Narciso; Riesco Rodríguez, Adrián; Verdejo López, José Alberto

    2007-01-01

    We introduce a declarative debugger for Maude functional modules, which correspond to executable specifications in membership equational logic. First we describe the construction of appropriate debugging trees for oriented equational and membership inferences. These trees are obtained as the result of collapsing in proof trees all those nodes whose correction does not need any justification. Since Maude supports the reflective features in its underlying logic, it includes a predefined...

  20. Modulation of Immune Functions by Foods

    Directory of Open Access Journals (Sweden)

    Shuichi Kaminogawa

    2004-01-01

    Full Text Available Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i studies examining the effect of foods in healthy individuals; (ii studies analyzing the effect of foods on patients with hypersensitivity; and (iii studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity or acquired immunity (T cell response, antibody production. Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity.

  1. On Functional Module Detection in Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Ina Koch

    2013-08-01

    Full Text Available Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models.

  2. Composite functional module inference: detecting cooperation between transcriptional regulation and protein interaction by mantel test

    Directory of Open Access Journals (Sweden)

    Su Fei

    2010-06-01

    Full Text Available Abstract Background Functional modules are basic units of cell function, and exploring them is important for understanding the organization, regulation and execution of cell processes. Functional modules in single biological networks (e.g., the protein-protein interaction network, have been the focus of recent studies. Functional modules in the integrated network are composite functional modules, which imply the complex relationships involving multiple biological interaction types, and detect them will help us understand the complexity of cell processes. Results We aimed to detect composite functional modules containing co-transcriptional regulation interaction, and protein-protein interaction, in our pre-constructed integrated network of Saccharomyces cerevisiae. We computationally extracted 15 composite functional modules, and found structural consistency between co-transcriptional regulation interaction sub-network and protein-protein interaction sub-network that was well correlated with their functional hierarchy. This type of composite functional modules was compact in structure, and was found to participate in essential cell processes such as oxidative phosphorylation and RNA splicing. Conclusions The structure of composite functional modules containing co-transcriptional regulation interaction, and protein-protein interaction reflected the cooperation of transcriptional regulation and protein function implementation, and was indicative of their important roles in essential cell functions. In addition, their structural and functional characteristics were closely related, and suggesting the complexity of the cell regulatory system.

  3. Modulation Based on Probability Density Functions

    Science.gov (United States)

    Williams, Glenn L.

    2009-01-01

    A proposed method of modulating a sinusoidal carrier signal to convey digital information involves the use of histograms representing probability density functions (PDFs) that characterize samples of the signal waveform. The method is based partly on the observation that when a waveform is sampled (whether by analog or digital means) over a time interval at least as long as one half cycle of the waveform, the samples can be sorted by frequency of occurrence, thereby constructing a histogram representing a PDF of the waveform during that time interval.

  4. Coupling a transient solvent extraction module with the separations and safeguards performance model.

    Energy Technology Data Exchange (ETDEWEB)

    DePaoli, David W. (Oak Ridge National Laboratory, Oak Ridge, TN); Birdwell, Joseph F. (Oak Ridge National Laboratory, Oak Ridge, TN); Gauld, Ian C. (Oak Ridge National Laboratory, Oak Ridge, TN); Cipiti, Benjamin B.; de Almeida, Valmor F. (Oak Ridge National Laboratory, Oak Ridge, TN)

    2009-10-01

    A number of codes have been developed in the past for safeguards analysis, but many are dated, and no single code is able to cover all aspects of materials accountancy, process monitoring, and diversion scenario analysis. The purpose of this work was to integrate a transient solvent extraction simulation module developed at Oak Ridge National Laboratory, with the Separations and Safeguards Performance Model (SSPM), developed at Sandia National Laboratory, as a first step toward creating a more versatile design and evaluation tool. The SSPM was designed for materials accountancy and process monitoring analyses, but previous versions of the code have included limited detail on the chemical processes, including chemical separations. The transient solvent extraction model is based on the ORNL SEPHIS code approach to consider solute build up in a bank of contactors in the PUREX process. Combined, these capabilities yield a more robust transient separations and safeguards model for evaluating safeguards system design. This coupling and initial results are presented. In addition, some observations toward further enhancement of separations and safeguards modeling based on this effort are provided, including: items to be addressed in integrating legacy codes, additional improvements needed for a fully functional solvent extraction module, and recommendations for future integration of other chemical process modules.

  5. Coupling a Transient Solvent Extraction Module with the Separations and Safeguards Performance Model

    Energy Technology Data Exchange (ETDEWEB)

    de Almeida, Valmor F [ORNL; Birdwell Jr, Joseph F [ORNL; DePaoli, David W [ORNL; Gauld, Ian C [ORNL

    2009-10-01

    A past difficulty in safeguards design for reprocessing plants is that no code existed for analysis and evaluation of the design. A number of codes have been developed in the past, but many are dated, and no single code is able to cover all aspects of materials accountancy, process monitoring, and diversion scenario analysis. The purpose of this work was to integrate a transient solvent extraction simulation module developed at Oak Ridge National Laboratory, with the SSPM Separations and Safeguards Performance Model, developed at Sandia National Laboratory, as a first step toward creating a more versatile design and evaluation tool. The SSPM was designed for materials accountancy and process monitoring analyses, but previous versions of the code have included limited detail on the chemical processes, including chemical separations. The transient solvent extraction model is based on the ORNL SEPHIS code approach to consider solute build up in a bank of contactors in the PUREX process. Combined, these capabilities yield a much more robust transient separations and safeguards model for evaluating safeguards system design. This coupling and the initial results are presented. In addition, some observations toward further enhancement of separations and safeguards modeling based on this effort are provided, including: items to be addressed in integrating legacy codes, additional improvements needed for a fully functional solvent extraction module, and recommendations for future integration of other chemical process modules.

  6. Granulocytes as modulators of dendritic cell function.

    Science.gov (United States)

    Breedveld, Annelot; Groot Kormelink, Tom; van Egmond, Marjolein; de Jong, Esther C

    2017-10-01

    Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4+ T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (Tregs). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs. Neutrophils, eosinophils, and basophils are rapidly recruited into infected tissues where their main function is to eliminate invading pathogens. Mast cells are tissue-resident granulocytes that also contribute to host defense against pathogens but have, thus far, primarily been associated with their detrimental roles in allergic diseases. Although granulocytes have always been considered essential in innate immunity, their ability to influence the development of adaptive immunity has long been overlooked. This view is now changing, as multiple studies showed significant modulating effects of granulocytes on key players of adaptive immunity, including DCs and lymphocytes. Neutrophils, eosinophils, basophils, and mast cells regulate recruitment and activation of DCs through the release of mediators or via direct cell-cell contact, thereby influencing antigen-specific T cell responses. In this review, we will summarize the current knowledge on the impact of granulocytes on DC functioning and the subsequent putative consequences of this cross-talk on T cell proliferation and polarization. Together, this overview underscores the importance of granulocyte-DC communication to establish optimal immune responses. © Society for Leukocyte Biology.

  7. FUMET: A fuzzy network module extraction technique for gene ...

    Indian Academy of Sciences (India)

    Supplementary figure 1. (A): Visualization of one of the network modules by GeneMania for dataset 4 (B): Visualization of one of the network modules by GeneMania for dataset 1 (C): Visualization of one of the network modules by GeneMania for dataset 3.

  8. Devil's Claw to suppress appetite--ghrelin receptor modulation potential of a Harpagophytum procumbens root extract.

    Directory of Open Access Journals (Sweden)

    Cristina Torres-Fuentes

    Full Text Available Ghrelin is a stomach-derived peptide that has been identified as the only circulating hunger hormone that exerts a potent orexigenic effect via activation of its receptor, the growth hormone secretagogue receptor (GHS-R1a. Hence, the ghrelinergic system represents a promising target to treat obesity and obesity-related diseases. In this study we analysed the GHS-R1a receptor activating potential of Harpagophytum procumbens, popularly known as Devil's Claw, and its effect on food intake in vivo. H. procumbens is an important traditional medicinal plant from Southern Africa with potent anti-inflammatory and analgesic effects. This plant has been also used as an appetite modulator but most evidences are anecdotal and to our knowledge, no clear scientific studies relating to appetite modulation have been done to this date. The ghrelin receptor activation potential of an extract derived from the dried tuberous roots of H. procumbens was analysed by calcium mobilization and receptor internalization assays in human embryonic kidney cells (Hek stably expressing the GHS-R1a receptor. Food intake was investigated in male C57BL/6 mice following intraperitoneal administration of H. procumbens root extract in ad libitum and food restricted conditions. Exposure to H. procumbens extract demonstrated a significant increased cellular calcium influx but did not induce subsequent GHS-R1a receptor internalization, which is a characteristic for full receptor activation. A significant anorexigenic effect was observed in male C57BL/6 mice following peripheral administration of H. procumbens extract. We conclude that H. procumbens root extract is a potential novel source for potent anti-obesity bioactives. These results reinforce the promising potential of natural bioactives to be developed into functional foods with weight-loss and weight maintenance benefits.

  9. Modeling of a Stacked Power Module for Parasitic Inductance Extraction

    Science.gov (United States)

    2017-09-15

    module was created in COMSOL Multiphysics Simulation Software. Within the AC/DC module of COMSOL , a magnetic-field physics simulation was performed...in the subsequent sections of this report. The COMSOL model geometry for the stacked power module is shown in Fig. 3. The purple regions represent...The various properties of this fluid, such as dielectric permittivity and resistivity, were manually defined in the COMSOL model. The lumped port

  10. Designing a Growing Functional Modules “Artificial Brain”

    Directory of Open Access Journals (Sweden)

    Jérôme Leboeuf-Pasquier

    2012-05-01

    Full Text Available

    The present paper illustrates the design process for the Growing Functional Modules (GFM learning based controller. GFM controllers are elaborated interconnecting four kinds of components: Global Goals, Acting Modules, Sensations and Sensing Modules. Global Goals trigger intrinsic motivations, Acting and Sensing Modules develop specific functionalities and Sensations provide the controlled system's feedback. GFM controllers learn to satisfy some predefined goals while interacting with the environment and thus should be considered as artificial brains. An example of the design process of a simple controller is provided herein to explain the inherent methodology, to exhibit the components' interconnections and to demonstrate the control process.

  11. A functional module-based exploration between inflammation and cancer in esophagus

    Science.gov (United States)

    Liu, Nannan; Li, Chunhua; Huang, Yan; Yi, Ying; Bo, Wanlan; Li, Chunmiao; Li, Yue; Hu, Yongfei; Li, Kongning; Wang, Hong; Zhuang, Liwei; Fan, Huihui; Wang, Dong

    2015-01-01

    Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, however, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage. In our study, we presented a functional module-based approach, in combination with multiple data resource (gene expression, protein-protein interactions (PPI), transcriptional and post-transcriptional regulations) to decipher the underlying links. Via mapping differentially expressed disease genes, functional disease modules were identified. As indicated, those common genes and interactions tended to play important roles in linking inflammation and cancer. Based on crosstalk analysis, we demonstrated that, although most disease genes were not shared by both kinds of modules, they might act through participating in the same or similar functions to complete the molecular links. Additionally, we applied pivot analysis to extract significant regulators for per significant crosstalk module pair. As shown, pivot regulators might manipulate vital parts of the module subnetworks, and then work together to bridge inflammation and cancer in esophagus. Collectively, based on our functional module analysis, we demonstrated that shared genes or interactions, significant crosstalk modules, and those significant pivot regulators were served as different functional parts underlying the molecular links between inflammation and cancer in esophagus. PMID:26489668

  12. Monaural and binaural subjective modulation transfer functions in simple reverberation

    DEFF Research Database (Denmark)

    2008-01-01

    The envelope of a signal is filtered by the transmission channel through which it passes. The amount of reduction for a given envelope, or modulation, frequency has been called the modulation transfer function (MTF) and can be derived from the impulse response of the transmission channel [Schroeder......, M.R. (1981) Modulation transfer-functions: Definition and measurement, Acustica, 49, 179-182]. The envelope of a speech signal is critical for intelligibility, and the speech transmission index (STI) predicts the intelligibility of speech through a given transmission channel based on its MTF...... [Houtgast, T. and Steeneken, H.J.M. (1973) Modulation transfer-function in room acoustics as a predictor of speech intelligibility, Acustica, 28, 66-73]. In the present study, the results of intensity modulation detection experiments with broad-band noise carriers are reported in monaural and binaural...

  13. Functional Task Analysis. A Training Module. School Personnel Utilization.

    Science.gov (United States)

    DeBloois, Michael; Melton, Raymond G.

    The School Personnel Utilization Project developed a series of modules to assist school personnel in building the necessary skills for the development of organizational change strategies and collaborative, collegial educational problem solving capabilities. This specific module on functional task analysis will assist the user in monitoring and…

  14. Searching for functional gene modules with interaction component models

    Directory of Open Access Journals (Sweden)

    Kaski Samuel

    2010-01-01

    Full Text Available Abstract Background Functional gene modules and protein complexes are being sought from combinations of gene expression and protein-protein interaction data with various clustering-type methods. Central features missing from most of these methods are handling of uncertainty in both protein interaction and gene expression measurements, and in particular capability of modeling overlapping clusters. It would make sense to assume that proteins may play different roles in different functional modules, and the roles are evidenced in their interactions. Results We formulate a generative probabilistic model for protein-protein interaction links and introduce two ways for including gene expression data into the model. The model finds interaction components, which can be interpreted as overlapping clusters or functional modules. We demonstrate the performance on two data sets of yeast Saccharomyces cerevisiae. Our methods outperform a representative set of earlier models in the task of finding biologically relevant modules having enriched functional classes. Conclusions Combining protein interaction and gene expression data with a probabilistic generative model improves discovery of modules compared to approaches based on either data source alone. With a fairly simple model we can find biologically relevant modules better than with alternative methods, and in addition the modules may be inherently overlapping in the sense that different interactions may belong to different modules.

  15. A fuzzy network module extraction technique for gene expression data

    Indian Academy of Sciences (India)

    2014-05-01

    May 1, 2014 ... Gluconeogenesis. 6.60e−19. GO:0070882. Cellular cell wall organization or biogenesis. 1.43e−25. GO:0030435. Sporulation resulting in formation of a cellular spore. Module2. 1.50e−15. GO:0006094. Gluconeogenesis. 6.95e−15. GO:0019319. Hexose biosynthetic process. 4.04e−19. GO:0007047.

  16. Ethanol extracts of Newbouldia laevis stem and leaves modulate ...

    African Journals Online (AJOL)

    Diabetes is known to involve oxidative stress and changes in antioxidant enzymes. Many plants metabolites have been shown to possess antioxidant activities, improving the effects of oxidative stress complications in diabetic conditions. This study evaluated the effects of extracts from Newbouldia laevis leaves and stem on ...

  17. Endothelial microparticles: Sophisticated vesicles modulating vascular function

    Science.gov (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

    2015-01-01

    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  18. CLARM: An integrative approach for functional modules discovery

    KAUST Repository

    Salem, Saeed M.

    2011-01-01

    Functional module discovery aims to find well-connected subnetworks which can serve as candidate protein complexes. Advances in High-throughput proteomic technologies have enabled the collection of large amount of interaction data as well as gene expression data. We propose, CLARM, a clustering algorithm that integrates gene expression profiles and protein protein interaction network for biological modules discovery. The main premise is that by enriching the interaction network by adding interactions between genes which are highly co-expressed over a wide range of biological and environmental conditions, we can improve the quality of the discovered modules. Protein protein interactions, known protein complexes, and gene expression profiles for diverse environmental conditions from the yeast Saccharomyces cerevisiae were used for evaluate the biological significance of the reported modules. Our experiments show that the CLARM approach is competitive to wellestablished module discovery methods. Copyright © 2011 ACM.

  19. PHEROMONAL MODULATION OF REPRODUCTIVE FUNCTION IN MAMMALS

    Directory of Open Access Journals (Sweden)

    Matthieu Keller

    2011-11-01

    Full Text Available Social olfactory signals, often known as pheromones, are powerful regulators of reproductive function. These chemosignals can be detected by two olfactory systems, namely the main or the accessory olfactory systems. While initially anatomically segregated, both systems converge functionally as they can detect and process overlapping sets of chemosignals. This convergence also takes place at the level of their central projections in the hypothalamus. It is probably at this level that future investigations will be needed. Indeed, if the physiology of both olfactory system and reproductive function are now quite well characterized, the interrelation between both systems is unclear. Among the many cell populations that can serve as targets or relays for the pheromonal information in the hypothalamus are GnRH cells or the recently discovered Kispeptin population which have been showed to be activated after pheromonal activation. However, many works will be needed before having a definitive picture.

  20. Nanomaterial-modulated autophagy: underlying mechanisms and functional consequences.

    Science.gov (United States)

    Zheng, Wei; Wei, Min; Li, Song; Le, Weidong

    2016-06-01

    Autophagy is an essential lysosome-dependent process that controls the quality of the cytoplasm and maintains cellular homeostasis, and dysfunction of this protein degradation system is correlated with various disorders. A growing body of evidence suggests that nanomaterials (NMs) have autophagy-modulating effects, thus predicting a valuable and promising application potential of NMs in the diagnosis and treatment of autophagy-related diseases. NMs exhibit unique physical, chemical and biofunctional properties, which may endow NMs with capabilities to modulate autophagy via various mechanisms. The present review highlights the impacts of various NMs on autophagy and their functional consequences. The possible underlying mechanisms for NM-modulated autophagy are also discussed.

  1. How MAP kinase modules function as robust, yet adaptable, circuits.

    Science.gov (United States)

    Tian, Tianhai; Harding, Angus

    2014-01-01

    Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution.

  2. Perceptual learning modules in mathematics: enhancing students' pattern recognition, structure extraction, and fluency.

    Science.gov (United States)

    Kellman, Philip J; Massey, Christine M; Son, Ji Y

    2010-04-01

    Learning in educational settings emphasizes declarative and procedural knowledge. Studies of expertise, however, point to other crucial components of learning, especially improvements produced by experience in the extraction of information: perceptual learning (PL). We suggest that such improvements characterize both simple sensory and complex cognitive, even symbolic, tasks through common processes of discovery and selection. We apply these ideas in the form of perceptual learning modules (PLMs) to mathematics learning. We tested three PLMs, each emphasizing different aspects of complex task performance, in middle and high school mathematics. In the MultiRep PLM, practice in matching function information across multiple representations improved students' abilities to generate correct graphs and equations from word problems. In the Algebraic Transformations PLM, practice in seeing equation structure across transformations (but not solving equations) led to dramatic improvements in the speed of equation solving. In the Linear Measurement PLM, interactive trials involving extraction of information about units and lengths produced successful transfer to novel measurement problems and fraction problem solving. Taken together, these results suggest (a) that PL techniques have the potential to address crucial, neglected dimensions of learning, including discovery and fluent processing of relations; (b) PL effects apply even to complex tasks that involve symbolic processing; and (c) appropriately designed PL technology can produce rapid and enduring advances in learning. Copyright © 2009 Cognitive Science Society, Inc.

  3. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  4. In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna canaliculus

    Directory of Open Access Journals (Sweden)

    Lawson John W

    2006-01-01

    Full Text Available Abstract Background Inflammation is a predominant characteristic of autoimmune diseases which is characterized by the increased expression of pro-inflammatory cytokines. Soon to be published work from our laboratory has shown that ingestion of Perna canaliculus prevents the development of autoimmune diseases such as Systemic Lupus Erythematosus and rheumatoid arthritis in laboratory animals. The current paper attempts to illustrate how Perna can alleviate inflammation by modulating inflammatory cytokines, cyclooxygenase enzymes and Immunoglobulin-G (IgG levels. Methods In the present study, hydrochloric acid [HCl] and Tween-20 were used to develop extracts of Perna. These extracts were assayed for protein content. Increasing concentrations of these extracts were then tested in cell culture for modulation of inflammatory cytokine, cyclooxygenase enzymes and IgG levels. Parallel tests were run using an available glycogen extract of Perna as a comparison to our in-house laboratory preparations. Results Tween-20 Perna extracts were found to be more stable and less toxic in cell culture than HCl digest of Perna. They also assayed higher in protein content that HCl extracts. Although both extracts inhibited IgG production in V2E9 hybridomas, Tween-20 extracts were more consistent in IgG suppression than HCl extracts. Overall Tween-20 extracts effectively decreased levels of TNF-α, IL-1, IL-2 and IL-6 as observed using cytokine bioassays. Twenty micrograms of Tween-20 Perna extracts induced such significant decreases in inflammatory cytokine production that when tested on sensitive cell lines, they very nearly abolished the decrease in viability induced by these cytokines. Tween-20 extracts effectively inhibited both COX-1 and COX-2 cyclooxygenase activity. As a comparison, the glycogen extract also demonstrated a similar though weaker effect on COX-1 and COX-2 enzymes. The active components of both extracts (Tween-20 and glycogen were observed to

  5. Guanidinium-based "molecular glues" for modulation of biomolecular functions.

    Science.gov (United States)

    Mogaki, Rina; Hashim, P K; Okuro, Kou; Aida, Takuzo

    2017-10-30

    Molecular adhesion based on multivalent interactions plays essential roles in various biological processes. Hence, "molecular glues" that can adhere to biomolecules may modulate biomolecular functions and therefore can be applied to therapeutics. This tutorial review describes design strategies for developing adhesive motifs for biomolecules based on multivalent interactions. We highlight a guanidinium ion-based salt-bridge as a key interaction for adhesion to biomolecules and discuss the application of molecular glues for manipulation of biomolecular assemblies, drug delivery systems, and modulation of biomolecular functions.

  6. Functionalized Solvents for Olefin Isomer Purification by Reactive Extractive Distillation

    NARCIS (Netherlands)

    Kuipers, N.J.M.; Wentink, A.E.; de Haan, A.B.; Scholtz, J.; Mulder, H.

    2007-01-01

    Olefin isomer separations are difficult, energy intensive and thus expensive. An overview is presented to investigate the feasibility of metal–ligand complexes as functionalized solvents applied in a novel separation technology, reactive extractive distillation, for the separation and purification

  7. FMFinder: A Functional Module Detector for PPI Networks

    Directory of Open Access Journals (Sweden)

    M. Modi

    2017-10-01

    Full Text Available Bioinformatics is an integrated area of data mining, statistics and computational biology. Protein-Protein Interaction (PPI network is the most important biological process in living beings. In this network a protein module interacts with another module and so on, forming a large network of proteins. The same set of proteins which takes part in the organic courses of biological actions is detected through the Function Module Detection method. Clustering process when applied in PPI networks is made of proteins which are part of a larger communication network. As a result of this, we can define the limits for module detection as well as clarify the construction of a PPI network. For understating the bio-mechanism of various living beings, a detailed study of FMFinder detection by clustering process is called for.

  8. Recycling WEEE: Extraction and concentration of silver from waste crystalline silicon photovoltaic modules.

    Science.gov (United States)

    Dias, Pablo; Javimczik, Selene; Benevit, Mariana; Veit, Hugo; Bernardes, Andréa Moura

    2016-11-01

    Photovoltaic modules (or panels) are important power generators with limited lifespans. The modules contain known pollutants and valuable materials such as silicon, silver, copper, aluminum and glass. Thus, recycling such waste is of great importance. To date, there have been few published studies on recycling silver from silicon photovoltaic panels, even though silicon technology represents the majority of the photovoltaic market. In this study, the extraction of silver from waste modules is justified and evaluated. It is shown that the silver content in crystalline silicon photovoltaic modules reaches 600g/t. Moreover, two methods to concentrate silver from waste modules were studied, and the use of pyrolysis was evaluated. In the first method, the modules were milled, sieved and leached in 64% nitric acid solution with 99% sodium chloride; the silver concentration yield was 94%. In the second method, photovoltaic modules were milled, sieved, subjected to pyrolysis at 500°C and leached in 64% nitric acid solution with 99% sodium chloride; the silver concentration yield was 92%. The first method is preferred as it consumes less energy and presents a higher yield of silver. This study shows that the use of pyrolysis does not assist in the extraction of silver, as the yield was similar for both methods with and without pyrolysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Acute administration of grape seed proanthocyanidin extract modulates energetic metabolism in skeletal muscle and BAT mitochondria.

    Science.gov (United States)

    Pajuelo, D; Díaz, S; Quesada, H; Fernández-Iglesias, A; Mulero, M; Arola-Arnal, A; Salvadó, M J; Bladé, C; Arola, L

    2011-04-27

    Proanthocyanidin consumption might reduce the risk of developing several pathologies, such as inflammation, oxidative stress and cardiovascular diseases. The beneficial effects of proanthocyanidins are attributed to their antioxidant properties, although they also can modulate gene expression at the transcriptional level. Little is known about the effect of proanthocyanidins on mitochondrial function and energy metabolism. In this context, the objective of this study was to determine the effect of an acute administration of grape seed proanthocyanidin extract (GSPE) on mitochondrial function and energy metabolism. To examine this effect, male Wistar rats fasted for fourteen hours, and then they were orally administered lard oil containing GSPE or were administered lard oil only. Liver, muscle and brown adipose tissue (BAT) were used to study enzymatic activity and gene expression of proteins related to energetic metabolism. Moreover, the gastrocnemius muscle and BAT mitochondria were used to perform high-resolution respirometry. The results showed that, after 5 h, the GSPE administration significantly lowers plasma triglycerides, free fatty acids, glycerol and urea concentrations. In skeletal muscle, GSPE lowers FATP1 mRNA levels and increases mitochondrial oxygen consumption, using pyruvate as the substrate, suggesting a promotion of glycosidic metabolism. Furthermore, GSPE increased the genetic expression of key genes in energy metabolism such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α), and modulated the enzyme activity of proteins, which are involved in the citric acid cycle and electron transport chain (ETC) in BAT. In conclusion, GSPE affects mainly the skeletal muscle and BAT mitochondria, increasing their oxidative capacity rapidly after acute supplementation.

  10. Exploring tomato gene functions based on coexpression modules using graph clustering and differential coexpression approaches.

    Science.gov (United States)

    Fukushima, Atsushi; Nishizawa, Tomoko; Hayakumo, Mariko; Hikosaka, Shoko; Saito, Kazuki; Goto, Eiji; Kusano, Miyako

    2012-04-01

    Gene-to-gene coexpression analysis provides fundamental information and is a promising approach for predicting unknown gene functions in plants. We investigated various associations in the gene expression of tomato (Solanum lycopersicum) to predict unknown gene functions in an unbiased manner. We obtained more than 300 microarrays from publicly available databases and our own hybridizations, and here, we present tomato coexpression networks and coexpression modules. The topological characteristics of the networks were highly heterogenous. We extracted 465 total coexpression modules from the data set by graph clustering, which allows users to divide a graph effectively into a set of clusters. Of these, 88% were assigned systematically by Gene Ontology terms. Our approaches revealed functional modules in the tomato transcriptome data; the predominant functions of coexpression modules were biologically relevant. We also investigated differential coexpression among data sets consisting of leaf, fruit, and root samples to gain further insights into the tomato transcriptome. We now demonstrate that (1) duplicated genes, as well as metabolic genes, exhibit a small but significant number of differential coexpressions, and (2) a reversal of gene coexpression occurred in two metabolic pathways involved in lycopene and flavonoid biosynthesis. Independent experimental verification of the findings for six selected genes was done using quantitative real-time polymerase chain reaction. Our findings suggest that differential coexpression may assist in the investigation of key regulatory steps in metabolic pathways. The approaches and results reported here will be useful to prioritize candidate genes for further functional genomics studies of tomato metabolism.

  11. Adrenal steroids as modulators of nerve cell function

    NARCIS (Netherlands)

    Kloet, E.R. de

    1984-01-01

    Adrenal steroids modulate the function of nerve cells. Some, but not all actions of these steroids take place after binding to intracellular receptor systems and translocation of the steroid-receptor complex into the cell nucleus. Studies on the rat brain revealed heterogeneity of receptors. One

  12. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Markers of liver function and inflammatory cytokines modulation by aerobic versus resisted exercise training for nonalcoholic steatohepatitis patients. Shehab M. Abd El-Kader1, Osama H. Al-Jiffri2, Fadwa M. Al-Shreef2. 1. Department of Physical Therapy, Faculty of Applied Medical Sciences, King Abdulaziz University. 2.

  13. A Study on the Design of Electronic SAMG Functional Modules

    Energy Technology Data Exchange (ETDEWEB)

    Park, S. H.; Kim, J. H.; Ahn, K. I. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    This paper describes a study on the design of e-SAMG functional modules. A study of for the design of e-SAMG was introduced. During an emergency status of a severe accident, the items for the functional module during a rapid and exact action are surveyed. The results are being implemented in e-SAMG. The operators can be supported through the use of e-SAMG. Based on the design of functional modules, the implementation will be accelerated and the refined design can also be applied. As a part of the Ministry of Science, ICT and future Planning (MSIP) Project, we at KAERI are developing electronic SAMG (e-SAMG, severe accident mitigation guideline) for general SAMG for nuclear power plants. Due to computerized trends, various efforts related to computer systems have been carried out for safety systems in nuclear power plants. In particular, since the Fukushima accident, unexpected accidents or extreme damages have become a concern. With this status, a rapid and exact confrontation such as a computerized attempt in SAMG has been tried. To develop an electronic SAMG, based on an analysis of the general SAMG, the architecture of e-SAMG was founded. The functional modules occupy important parts in the e-SAMG.

  14. Identification of fractional order systems using modulating functions method

    KAUST Repository

    Liu, Dayan

    2013-06-01

    The modulating functions method has been used for the identification of linear and nonlinear systems. In this paper, we generalize this method to the on-line identification of fractional order systems based on the Riemann-Liouville fractional derivatives. First, a new fractional integration by parts formula involving the fractional derivative of a modulating function is given. Then, we apply this formula to a fractional order system, for which the fractional derivatives of the input and the output can be transferred into the ones of the modulating functions. By choosing a set of modulating functions, a linear system of algebraic equations is obtained. Hence, the unknown parameters of a fractional order system can be estimated by solving a linear system. Using this method, we do not need any initial values which are usually unknown and not equal to zero. Also we do not need to estimate the fractional derivatives of noisy output. Moreover, it is shown that the proposed estimators are robust against high frequency sinusoidal noises and the ones due to a class of stochastic processes. Finally, the efficiency and the stability of the proposed method is confirmed by some numerical simulations.

  15. Multi-functional Electric Module for a Vehicle

    Science.gov (United States)

    Bluethmann, William J. (Inventor); Waligora, Thomas M. (Inventor); Fraser-Chanpong, Nathan (Inventor); Reed, Ryan (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Figuered, Joshua M. (Inventor); Herrera, Eduardo (Inventor); Markee, Mason M. (Inventor)

    2015-01-01

    A multi-functional electric module (eModule) is provided for a vehicle having a chassis, a master controller, and a drive wheel having a propulsion-braking module. The eModule includes a steering control assembly, mounting bracket, propulsion control assembly, brake controller, housing, and control arm. The steering control assembly includes a steering motor controlled by steering controllers in response to control signals from the master controller. A mounting feature of the bracket connects to the chassis. The propulsion control assembly and brake controller are in communication with the propulsion-braking module. The control arm connects to the lower portion and contains elements of a suspension system, with the control arm being connectable to the drive wheel via a wheel input/output block. The controllers are responsive to the master controller to control a respective steering, propulsion, and braking function. The steering motor may have a dual-wound stator with windings controlled via the respective steering controllers.

  16. Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila

    Science.gov (United States)

    Oortveld, Merel A. W.; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G.; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A.; Schenck, Annette

    2013-01-01

    Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules. PMID:24204314

  17. Proper Analytic Point Spread Function for Lateral Modulation

    Science.gov (United States)

    Sumi, Chikayoshi; Shimizu, Kunio; Matsui, Norihiko

    2010-07-01

    For ultrasonic lateral modulation for the imaging and measurement of tissue motion, better envelope shapes of the point spread function (PSF) than of a parabolic function are searched for within analytic functions or windows on the basis of the knowledge of the ideal shape of PSF previously obtained, i.e., having a large full width at half maximum and short feet. Through simulation of displacement vector measurement, better shapes are determined. As a better shape, a new window is obtained from a Turkey window by changing Hanning windows by power functions with an order larger than the second order. The order of measurement accuracies obtained is as follows, the new window > rectangular window > power function with a higher order > parabolic function > Akaike window.

  18. Yellow Mealworm Protein for Food Purposes - Extraction and Functional Properties

    Science.gov (United States)

    Zhao, Xue; Vázquez-Gutiérrez, José Luis; Johansson, Daniel P.; Landberg, Rikard; Langton, Maud

    2016-01-01

    A protocol for extraction of yellow mealworm larvae proteins was established, conditions were evaluated and the resulting protein extract was characterised. The freeze-dried yellow mealworm larvae contained around 33% fat, 51% crude protein and 43% true protein on a dry matter basis. The true protein content of the protein extract was about 75%, with an extraction rate of 70% under optimised extraction conditions using 0.25 M NaOH, a NaOH solution:ethanol defatted worm ratio of 15:1 mL/g, 40°C for 1 h and extraction twice. The protein extract was a good source of essential amino acids. The lowest protein solubility in distilled water solution was found between pH 4 and 5, and increased with either increasing or decreasing pH. Lower solubility was observed in 0.5 M NaCl solution compared with distilled water. The rheological tests indicated that temperature, sample concentration, addition of salt and enzyme, incubation time and pH alterations influenced the elastic modulus of yellow mealworm protein extract (YMPE). These results demonstrate that the functional properties of YMPE can be modified for different food applications. PMID:26840533

  19. Yellow Mealworm Protein for Food Purposes - Extraction and Functional Properties.

    Directory of Open Access Journals (Sweden)

    Xue Zhao

    Full Text Available A protocol for extraction of yellow mealworm larvae proteins was established, conditions were evaluated and the resulting protein extract was characterised. The freeze-dried yellow mealworm larvae contained around 33% fat, 51% crude protein and 43% true protein on a dry matter basis. The true protein content of the protein extract was about 75%, with an extraction rate of 70% under optimised extraction conditions using 0.25 M NaOH, a NaOH solution:ethanol defatted worm ratio of 15:1 mL/g, 40°C for 1 h and extraction twice. The protein extract was a good source of essential amino acids. The lowest protein solubility in distilled water solution was found between pH 4 and 5, and increased with either increasing or decreasing pH. Lower solubility was observed in 0.5 M NaCl solution compared with distilled water. The rheological tests indicated that temperature, sample concentration, addition of salt and enzyme, incubation time and pH alterations influenced the elastic modulus of yellow mealworm protein extract (YMPE. These results demonstrate that the functional properties of YMPE can be modified for different food applications.

  20. Immune-Modulating Activity of Extract Prepared from Mycelial Culture of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes).

    Science.gov (United States)

    Jang, Sun-Hee; Kim, Sae-Hae; Lee, Ha-Yan; Jang, Seung-Hwan; Jang, Hyonseok; Chae, Soo-Wan; Jung, Su-Jin; So, Byung-Ok; Ha, Ki-Chan; Sin, Hong-Sig; Jang, Yong-Suk

    2015-01-01

    Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild O. sinensis is becoming increasingly rare in its natural habitats, and its price is out of reach for clinical practice. For these reasons, development of a standardized alternative is a great focus of research to allow the use of O. sinensis as a medicine. To develop an alternative for wild O. sinensis, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vivo immune-modulating effect of CBG-CS-2 in mice. Oral administration of CBG-CS-2 supported splenocyte stimulation and enhanced Th1-type cytokine expression from the splenocytes. Importantly, the same treatment significantly enhanced the natural killer cell activity of the splenocytes. Finally, oral administration of CBG-CS-2 enhanced the potential for inflammatory responses. Together, these findings indicate that the mycelial culture extract prepared from O. sinensis exhibited immune-modulating activity and suggest its possible use in the treatment of diseases caused by abnormal immune function.

  1. Robust fractional order differentiators using generalized modulating functions method

    KAUST Repository

    Liu, Dayan

    2015-02-01

    This paper aims at designing a fractional order differentiator for a class of signals satisfying a linear differential equation with unknown parameters. A generalized modulating functions method is proposed first to estimate the unknown parameters, then to derive accurate integral formulae for the left-sided Riemann-Liouville fractional derivatives of the studied signal. Unlike the improper integral in the definition of the left-sided Riemann-Liouville fractional derivative, the integrals in the proposed formulae can be proper and be considered as a low-pass filter by choosing appropriate modulating functions. Hence, digital fractional order differentiators applicable for on-line applications are deduced using a numerical integration method in discrete noisy case. Moreover, some error analysis are given for noise error contributions due to a class of stochastic processes. Finally, numerical examples are given to show the accuracy and robustness of the proposed fractional order differentiators.

  2. Determination of the modulation transfer function in betatron tomography

    Science.gov (United States)

    Kayralapov, D.; Mamyrbayev, T.; Osipov, S. P.; Chakhlov, S. V.

    2017-08-01

    Spatial resolution of high-energy computed tomography is experimentally studied on the basis of X-ray inspection of a steel cylinder to assess the operability of the system [1, 2]. To determine the spatial resolution in the energy range of X-ray radiation from 1 to 4 MeV, the modulation transfer function with a preliminary filtering of radiation by a copper plate of 4 mm thickness was measured. The effect of beam hardening and correction of ring artifacts is studied. The modulation transfer function is determined using the Brucker microCT software. Experimental studies were conducted in the Russian-Chinese scientific laboratory for X-ray control and inspection of the Tomsk Polytechnic University [3, 4].

  3. Human skin hypoxia modulates cerebrovascular and autonomic functions.

    Directory of Open Access Journals (Sweden)

    Olivia Pucci

    Full Text Available Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen or skin normoxia (with air. The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.

  4. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    Directory of Open Access Journals (Sweden)

    II Kim Jae

    2010-10-01

    Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  5. Degree of musical expertise modulates higher order brain functioning.

    Science.gov (United States)

    Oechslin, Mathias S; Van De Ville, Dimitri; Lazeyras, François; Hauert, Claude-Alain; James, Clara E

    2013-09-01

    Using functional magnetic resonance imaging, we show for the first time that levels of musical expertise stepwise modulate higher order brain functioning. This suggests that degree of training intensity drives such cerebral plasticity. Participants (non-musicians, amateurs, and expert musicians) listened to a comprehensive set of specifically composed string quartets with hierarchically manipulated endings. In particular, we implemented 2 irregularities at musical closure that differed in salience but were both within the tonality of the piece (in-key). Behavioral sensitivity scores (d') of both transgressions perfectly separated participants according to their level of musical expertise. By contrasting brain responses to harmonic transgressions against regular endings, functional brain imaging data showed compelling evidence for stepwise modulation of brain responses by both violation strength and expertise level in a fronto-temporal network hosting universal functions of working memory and attention. Additional independent testing evidenced an advantage in visual working memory for the professionals, which could be predicted by musical training intensity. The here introduced findings of brain plasticity demonstrate the progressive impact of musical training on cognitive brain functions that may manifest well beyond the field of music processing.

  6. A solvent-extraction module for cyclotron production of high-purity technetium-99m.

    Science.gov (United States)

    Martini, Petra; Boschi, Alessandra; Cicoria, Gianfranco; Uccelli, Licia; Pasquali, Micòl; Duatti, Adriano; Pupillo, Gaia; Marengo, Mario; Loriggiola, Massimo; Esposito, Juan

    2016-12-01

    The design and fabrication of a fully-automated, remotely controlled module for the extraction and purification of technetium-99m (Tc-99m), produced by proton bombardment of enriched Mo-100 molybdenum metallic targets in a low-energy medical cyclotron, is here described. After dissolution of the irradiated solid target in hydrogen peroxide, Tc-99m was obtained under the chemical form of 99mTcO4-, in high radionuclidic and radiochemical purity, by solvent extraction with methyl ethyl ketone (MEK). The extraction process was accomplished inside a glass column-shaped vial especially designed to allow for an easy automation of the whole procedure. Recovery yields were always >90% of the loaded activity. The final pertechnetate saline solution Na99mTcO4, purified using the automated module here described, is within the Pharmacopoeia quality control parameters and is therefore a valid alternative to generator-produced 99mTc. The resulting automated module is cost-effective and easily replicable for in-house production of high-purity Tc-99m by cyclotrons. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Functional neurological symptoms modulate processing of emotionally salient stimuli.

    Science.gov (United States)

    Fiess, Johanna; Rockstroh, Brigitte; Schmidt, Roger; Wienbruch, Christian; Steffen, Astrid

    2016-12-01

    Dysfunctional emotion processing has been discussed as a contributing factor to functional neurological symptoms (FNS) in the context of conversion disorder, and refers to blunted recognition and the expression of one's own feelings. However, the emotion processing components characteristic for FNS and/or relevant for conversion remain to be specified. With this goal, the present study targeted the initial, automatic discrimination of emotionally salient stimuli. The magnetoencephalogram (MEG) was monitored in 21 patients with functional weakness and/or sensory disturbance subtypes of FNS and 21 healthy comparison participants (HC) while they passively watched 600 emotionally arousing, pleasant, unpleasant or neutral stimuli in a rapid serial visual presentation (RSVP) design. Neuromagnetic activity was analyzed 110-330ms following picture onset in source space for prior defined posterior and central regions of interest. As early as 110ms and across presentation interval, posterior neural activity modulation by picture category was similar in both groups, despite smaller initial (110-150ms) overall and posterior power in patients with FNS. The initial activity modulation by picture category was also evident in the left sensorimotor area in patients with FNS, but not significant in HC. Similar activity modulation by emotional picture category in patients with FNS and HC suggests that the fast, automatic detection of emotional salience is unchanged in patients with FNS, but involves an emotion-processing network spanning posterior and sensorimotor areas. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pharmacological Modulation of Functional Phenotypes of Microglia in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Gyun Jee Song

    2017-05-01

    Full Text Available Microglia are the resident innate immune cells of the central nervous system that mediate brain homeostasis maintenance. Microglia-mediated neuroinflammation is a hallmark shared by various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Numerous studies have shown microglial activation phenotypes to be heterogeneous; however, these microglial phenotypes can largely be categorized as being either M1 or M2 type. Although the specific classification of M1 and M2 functionally polarized microglia remains a topic for debate, the use of functional modulators of microglial phenotypes as potential therapeutic approaches for the treatment of neurodegenerative diseases has garnered considerable attention. This review discusses M1 and M2 microglial phenotypes and their relevance in neurodegenerative disease models, as described in recent literature. The modulation of microglial polarization toward the M2 phenotype may lead to development of future therapeutic and preventive strategies for neuroinflammatory and neurodegenerative diseases. Thus, we focus on recent studies of microglial polarization modulators, with a particular emphasis on the small-molecule compounds and their intracellular target proteins.

  9. Functional modules of sigma factor regulons guarantee adaptability and evolvability

    Science.gov (United States)

    Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-02-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.

  10. CONSIDERATIONS FOR THE DEVELOPMENT OF A DEVICE FOR THE DECOMMISSIONING OF THE HORIZONTAL FUEL CHANNELS IN THE CANDU 6 NUCLEAR REACTOR. PART 9 - CUTTING AND EXTRACTING DEVICE FUNCTIONING

    Directory of Open Access Journals (Sweden)

    Constantin POPESCU

    2015-05-01

    Full Text Available This paper presents a constructive solution proposed by the authors in order to achieve of a cutting and extracting device for the decommissioning of the horizontal fuel channels in the CANDU 6 nuclear reactor. The Cutting and Extraction Device (CED performs the dismantling, cutting and extraction of the fuel channel components. It's a flexible and modular device, which is designed to work inside the fuel channel and has the following functions: moving with variable speed, temperature monitoring and video surveillance inside the pipe, unblock and extract the channel closure plug (from End Fitting - EF, unblock and extract the channel shield plug (from Lattice Tube - LT, block and cut the middle of the pressure tube, block and cut the end of the pressure tube, block and extract the half of pressure tube. The Cutting and Extraction Device (CED consists of following modules: guiding-fixing module, traction modules, cutting module, guiding-extracting module and flexible elements for modules connecting. The guiding-fixing module is equipped with elastic guiding rollers and fixing claws in working position, the traction modules are provided with variable pitch rollers for allowing variable travel speed through the fuel channel. The cutting module is positioned in the middle of the device and it is equipped with three knife rolls for pressure tube cutting, using a system for cutting place video surveillance and pyrometers for monitoring cutting place temperature. The Cutting and Extraction Device (CED is fully automated, connected by wires to a Programmable Logic Controller (PLC and controlled from a Human Machine Interface (HMI. The design of the Cutting and Extraction Device (CED shall be achieved according to the particular features of the fuel channel components to be dismantled and to ensure radiation protection of workers.

  11. Estimation of presampling modulation transfer function in synchrotron radiation microtomography

    CERN Document Server

    Mizutani, Ryuta; Takeuchi, Akihisa; Uesugi, Kentaro; Suzuki, Yoshio

    2016-01-01

    The spatial resolution achieved by recent synchrotron radiation microtomographs should be estimated from the modulation transfer function (MTF) on the micrometer scale. Step response functions of a synchrotron radiation microtomograph were determined by the slanted edge method by using high-precision surfaces of diamond crystal and ion-milled aluminum wire. Tilted reconstruction was introduced to enable any edge to be used as the slanted edge by defining the reconstruction pixel matrix in an arbitrary orientation. MTFs were estimated from the step response functions of the slanted edges. The obtained MTFs coincided with MTF values estimated from square-wave patterns milled on the aluminum surface. Although x-ray refraction influences should be taken into account to evaluate MTFs, any flat surfaces with nanometer roughness can be used to determine the spatial resolutions of microtomographs.

  12. Modulation of Dendritic Cell Function by Leishmania Parasites1

    Science.gov (United States)

    Soong, Lynn

    2009-01-01

    The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN-γ-stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses. PMID:18354154

  13. Modulation of dendritic cell function by Leishmania parasites.

    Science.gov (United States)

    Soong, Lynn

    2008-04-01

    The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN-gamma-stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses.

  14. Cholinergic modulation of the hippocampal region and memory function.

    Science.gov (United States)

    Haam, Juhee; Yakel, Jerrel L

    2017-08-01

    Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  15. Requirements for a Dynamic Solvent Extraction Module to Support Development of Advanced Technologies for the Recycle of Used Nuclear Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Jack Law; Veronica Rutledge; Candido Pereira; Jackie Copple; Kurt Frey; John Krebs; Laura Maggos; Kevin Nichols; Kent Wardle; Pratap Sadasivan; Valmor DeAlmieda; David Depaoli

    2011-06-01

    The Department of Energy's Nuclear Energy Advanced Modeling and Simulation (NEAMS) Program has been established to create and deploy next generation, verified and validated nuclear energy modeling and simulation capabilities for the design, implementation, and operation of future nuclear energy systems to improve the U.S. energy security. As part of the NEAMS program, Integrated Performance and Safety Codes (IPSC's) are being produced to significantly advance the status of modeling and simulation of energy systems beyond what is currently available to the extent that the new codes be readily functional in the short term and extensible in the longer term. The four IPSC areas include Safeguards and Separations, Reactors, Fuels, and Waste Forms. As part of the Safeguards and Separations (SafeSeps) IPSC effort, interoperable process models are being developed that enable dynamic simulation of an advanced separations plant. A SafeSepss IPSC 'toolkit' is in development to enable the integration of separation process modules and safeguards tools into the design process by providing an environment to compose, verify and validate a simulation application to be used for analysis of various plant configurations and operating conditions. The modules of this toolkit will be implemented on a modern, expandable architecture with the flexibility to explore and evaluate a wide range of process options while preserving their stand-alone usability. Modules implemented at the plant-level will initially incorporate relatively simple representations for each process through a reduced modeling approach. Final versions will incorporate the capability to bridge to subscale models to provide required fidelity in chemical and physical processes. A dynamic solvent extraction model and its module implementation are needed to support the development of this integrated plant model. As a stand-alone application, it will also support solvent development of extraction flowsheets

  16. Automatically extracting functionally equivalent proteins from SwissProt

    Directory of Open Access Journals (Sweden)

    Martin Andrew CR

    2008-10-01

    Full Text Available Abstract Background There is a frequent need to obtain sets of functionally equivalent homologous proteins (FEPs from different species. While it is usually the case that orthology implies functional equivalence, this is not always true; therefore datasets of orthologous proteins are not appropriate. The information relevant to extracting FEPs is contained in databanks such as UniProtKB/Swiss-Prot and a manual analysis of these data allow FEPs to be extracted on a one-off basis. However there has been no resource allowing the easy, automatic extraction of groups of FEPs – for example, all instances of protein C. We have developed FOSTA, an automatically generated database of FEPs annotated as having the same function in UniProtKB/Swiss-Prot which can be used for large-scale analysis. The method builds a candidate list of homologues and filters out functionally diverged proteins on the basis of functional annotations using a simple text mining approach. Results Large scale evaluation of our FEP extraction method is difficult as there is no gold-standard dataset against which the method can be benchmarked. However, a manual analysis of five protein families confirmed a high level of performance. A more extensive comparison with two manually verified functional equivalence datasets also demonstrated very good performance. Conclusion In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and

  17. Brassica rapa hairy root extracts promote skin depigmentation by modulating melanin production and distribution.

    Science.gov (United States)

    Sena, Luigi Michele; Zappelli, Claudia; Apone, Fabio; Barbulova, Ani; Tito, Annalisa; Leone, Antonella; Oliviero, Teresa; Ferracane, Rosalia; Fogliano, Vincenzo; Colucci, Gabriella

    2017-07-03

    Skin whitening products, used for ages by Asian people for cultural and esthetic purposes, are very popular nowadays in Western countries as well, where the need to inhibit skin spots after sun exposure has become not only a cosmetic but also a health-related issue. Thus, the development of effective and safe depigmenting agents derived from natural products gets continuous attention by cosmetic brands and consumers. The aim of this study was to determine the effects of two preparations, obtained from the hairy root cultures of the species Brassica rapa, on melanogenesis and the expression of the extracellular matrix proteins involved in a correct pigment distribution. The two preparations, obtained by water-ethanol extraction and by digestion of cell-wall glycoproteins of the root cells, were chemically characterized and tested on skin cell cultures and on human skin explants to investigate on their dermatological activities. Both the extracts were able to decrease melanin synthesis pathway in melanocytes and modulate the expression of genes involved in melanin distribution. One of the extracts was also effective in inducing the expression of laminin-5 and collagen IV, involved into the maintenance of tissue integrity. The two extracts, when tested together on human skin explants, demonstrated a good synergic hypopigmenting activity. Taken together, the results indicate that the extracts from B. rapa root cultures can be employed as cosmetic active ingredients in skin whitening products and as potential therapeutic agents for treating pigmentation disorders. © 2017 Wiley Periodicals, Inc.

  18. Extracting the Green's function from measurements of the energy flux.

    Science.gov (United States)

    Snieder, Roel; Douma, Huub; Vasconcelos, Ivan

    2012-04-01

    Existing methods for Green's function extraction give the Green's function from the correlation of field fluctuations recorded at those points. In this work it is shown that the Green's function for acoustic waves can be retrieved from measurements of the integrated energy flux through a closed surface taken from three experiments where two time-harmonic sources first operate separately, and then simultaneously. This makes it possible to infer the Green's function in acoustics from measurements of the energy flux through an arbitrary closed surface surrounding both sources. The theory is also applicable to quantum mechanics where the Green's function can be retrieved from measurement of the flux of scattered particles through a closed surface.

  19. Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators

    Directory of Open Access Journals (Sweden)

    Lulu Yao

    2017-01-01

    Full Text Available The N-methyl-D-aspartate receptors (NMDARs are subtype glutamate receptors that play important roles in excitatory neurotransmission and synaptic plasticity. Their hypo- or hyperactivation are proposed to contribute to the genesis or progression of various brain diseases, including stroke, schizophrenia, depression, and Alzheimer’s disease. Past efforts in targeting NMDARs for therapeutic intervention have largely been on inhibitors of NMDARs. In light of the discovery of NMDAR hypofunction in psychiatric disorders and perhaps Alzheimer’s disease, efforts in boosting NMDAR activity/functions have surged in recent years. In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs.

  20. Propeptides as modulators of functional activity of proteases.

    Science.gov (United States)

    Demidyuk, Ilya V; Shubin, Andrey V; Gasanov, Eugene V; Kostrov, Sergey V

    2010-10-01

    Most proteases are synthesized in the cell as precursor-containing propeptides. These structural elements can determine the folding of the cognate protein, function as an inhibitor/activator peptide, mediate enzyme sorting, and mediate the protease interaction with other molecules and supramolecular structures. The data presented in this review demonstrate modulatory activity of propeptides irrespective of the specific mechanism of action. Changes in propeptide structure, sometimes minor, can crucially alter protein function in the living organism. Modulatory activity coupled with high variation allows us to consider propeptides as specific evolutionary modules that can transform biological properties of proteases without significant changes in the highly conserved catalytic domains. As the considered properties of propeptides are not unique to proteases, propeptide-mediated evolution seems to be a universal biological mechanism.

  1. Module-based quality system functionality evaluation in production logistics

    Energy Technology Data Exchange (ETDEWEB)

    Khabbazi, M.R.; Wikander, J.; Onori, M.; Maffei, A.; Chen, D.

    2016-07-01

    This paper addresses a comprehensive modeling and functionality evaluation of a module-based quality system in production logistics at the highest domain abstract level of business processes. All domain quality business processes and quality data transactions are modeled using BPMN and UML tools and standards at the business process and data modeling. A modular web-based prototype is developed to evaluate the models addressing the quality information system functionality requirements and modularity in production logistics through data scenarios and data queries. Using the object-oriented technique in design at the highest domain level, the proposed models are subject further development in the lower levels for the implementing case. The models are specifically able to manipulate all quality operations including remedy and control in a lot-based make-to-order production logistics system as an individual module. Due to the specification of system as domain design structure, all proposed BPMs, data models, and the actual database prototype are seen referential if not a solution as a practical “to-be” quality business process re-engineering template. This paper sets out to provide an explanatory approach using different practical technique at modeling steps as well as the prototype implementation. (Author)

  2. Dopaminergic modulation of cortical function in patients with Parkinson's disease.

    Science.gov (United States)

    Mattay, Venkata S; Tessitore, Alessandro; Callicott, Joseph H; Bertolino, Alessandro; Goldberg, Terry E; Chase, Thomas N; Hyde, Thomas M; Weinberger, Daniel R

    2002-02-01

    Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine-replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine-replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine-replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of

  3. Circuit multiplies pulse width modulation, exhibits linear transfer function

    Science.gov (United States)

    Carlson, A. W.; Furciniti, A.

    1967-01-01

    Modulation multiplier provides a simple means of multiplying the width modulation of a pulse train by a constant factor. It operates directly on a pulse width modulated input signal to generate an output pulse train having a greater degree of width modulation than the input signal.

  4. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells.

    Science.gov (United States)

    Kwon, Ho-Keun; Hwang, Ji-Sun; Lee, Choong-Gu; So, Jae-Seon; Sahoo, Anupama; Im, Chang-Rok; Jeon, Won Kyung; Ko, Byoung Seob; Lee, Sung Haeng; Park, Zee Yong; Im, Sin-Hyeog

    2011-02-28

    To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII(+)) and CD11c(+) dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H(3)]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue. Treatment with cinnamon extract inhibited maturation of MHCII(+) APCs or CD11c(+) dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) CD4(+) T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression

  5. Algorithm for systematic peak extraction from atomic pair distribution functions.

    Science.gov (United States)

    Granlund, L; Billinge, S J L; Duxbury, P M

    2015-07-01

    The study presents an algorithm, ParSCAPE, for model-independent extraction of peak positions and intensities from atomic pair distribution functions (PDFs). It provides a statistically motivated method for determining parsimony of extracted peak models using the information-theoretic Akaike information criterion (AIC) applied to plausible models generated within an iterative framework of clustering and chi-square fitting. All parameters the algorithm uses are in principle known or estimable from experiment, though careful judgment must be applied when estimating the PDF baseline of nanostructured materials. ParSCAPE has been implemented in the Python program SrMise. Algorithm performance is examined on synchrotron X-ray PDFs of 16 bulk crystals and two nanoparticles using AIC-based multimodeling techniques, and particularly the impact of experimental uncertainties on extracted models. It is quite resistant to misidentification of spurious peaks coming from noise and termination effects, even in the absence of a constraining structural model. Structure solution from automatically extracted peaks using the Liga algorithm is demonstrated for 14 crystals and for C60. Special attention is given to the information content of the PDF, theory and practice of the AIC, as well as the algorithm's limitations.

  6. Structuring detergents for extracting and stabilizing functional membrane proteins.

    Directory of Open Access Journals (Sweden)

    Rima Matar-Merheb

    Full Text Available BACKGROUND: Membrane proteins are privileged pharmaceutical targets for which the development of structure-based drug design is challenging. One underlying reason is the fact that detergents do not stabilize membrane domains as efficiently as natural lipids in membranes, often leading to a partial to complete loss of activity/stability during protein extraction and purification and preventing crystallization in an active conformation. METHODOLOGY/PRINCIPAL FINDINGS: Anionic calix[4]arene based detergents (C4Cn, n=1-12 were designed to structure the membrane domains through hydrophobic interactions and a network of salt bridges with the basic residues found at the cytosol-membrane interface of membrane proteins. These compounds behave as surfactants, forming micelles of 5-24 nm, with the critical micellar concentration (CMC being as expected sensitive to pH ranging from 0.05 to 1.5 mM. Both by 1H NMR titration and Surface Tension titration experiments, the interaction of these molecules with the basic amino acids was confirmed. They extract membrane proteins from different origins behaving as mild detergents, leading to partial extraction in some cases. They also retain protein functionality, as shown for BmrA (Bacillus multidrug resistance ATP protein, a membrane multidrug-transporting ATPase, which is particularly sensitive to detergent extraction. These new detergents allow BmrA to bind daunorubicin with a Kd of 12 µM, a value similar to that observed after purification using dodecyl maltoside (DDM. They preserve the ATPase activity of BmrA (which resets the protein to its initial state after drug efflux much more efficiently than SDS (sodium dodecyl sulphate, FC12 (Foscholine 12 or DDM. They also maintain in a functional state the C4Cn-extracted protein upon detergent exchange with FC12. Finally, they promote 3D-crystallization of the membrane protein. CONCLUSION/SIGNIFICANCE: These compounds seem promising to extract in a functional state

  7. Extracts from Tribulus species may modulate platelet adhesion by interfering with arachidonic acid metabolism.

    Science.gov (United States)

    Olas, Beata; Hamed, Arafa I; Oleszek, Wieslaw; Stochmal, Anna

    2015-01-01

    The present work was designed to study the effects of crude extracts from Tribulus pterocarpus, T. pentandrus and T. parvispinus on selected biological functions of human blood platelets in vitro. Platelet suspensions were pre-incubated with extracts from aerial parts of T. pterocarpus, T. pentandrus and T. parvispinus, at the final concentrations of 0.5, 5 and 50 µg/ml. Then, for platelet activation thrombin, was used. The effects of crude extracts from T. pterocarpus, T. pentandrus and T. parvispinus on adhesion of blood platelets to collagen were determined by method according to Tuszynski and Murphy. Arachidonic acid metabolism was measured by the level of thiobarbituric acid reactive substances (TBARS). In these studies we also compared the action of tested crude plant extracts with the effects of the polyphenolic fraction isolated from aerial parts of T. pterocarpus, which has antiplatelet and antioxidative properties. The performed assays demonstrated that the tested crude extract from T. pterocarpus and the phenolic fraction from T. pterocarpus might influence the platelet functions in vitro. The inhibitory, concentration-dependent effects of this tested extract and its phenolic fraction on adhesion of resting platelets and thrombin - stimulated platelets to collagen was found. We also observed that the crude extract from T. pterocarpus, like the polyphenolic fraction from T. pterocarpus reduced TBARS production in blood platelets. In the comparative studies, the tested crude extract from T. pterocarpus was not found to be more effective antiplatelet factor, than the polyphenolic fraction from this plant. The results obtained suggest that T. pterocarpus may be a promising source of natural compounds, valuable in the prevention of the enhanced activity of blood platelets in numerous cardiovascular diseases.

  8. Modulating functional and dysfunctional mentalizing by transcranial magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tobias eSchuwerk

    2014-11-01

    Full Text Available Mentalizing, the ability to attribute mental states to others and oneself, is a cognitive function with high relevance for social interactions. Recent neuroscientific research has increasingly contributed to attempts to decompose this complex social cognitive function into constituting neurocognitive building blocks. Additionally, clinical research that focuses on social cognition to find links between impaired social functioning and neurophysiological deviations has accumulated evidence that mentalizing is affected in most psychiatric disorders. Recently, both lines of research have started to employ transcranial magnetic stimulation: the first to modulate mentalizing in order to specify its neurocognitive components, the latter to treat impaired mentalizing in clinical conditions. This review integrates findings of these two different approaches to draw a more detailed picture of the neurocognitive basis of mentalizing and its deviations in psychiatric disorders. Moreover, we evaluate the effectiveness of hitherto employed stimulation techniques and protocols, paradigms and outcome measures. Based on this overview we highlight new directions for future research on the neurocognitive basis of functional and dysfunctional social cognition.

  9. Immune modulation effect of porcine placenta extracts in weaned the pig.

    Science.gov (United States)

    Lee, K H; Park, Hyun Jung; Seo, H G; Kim, J H; Lim, G S; Lee, W Y; Kim, N H; Kim, J H; Lee, J H; Jung, H S; Sung, S H; Song, H

    2013-05-01

    In a previous study, we established a collection of appropriate porcine placental extracts using PBS at 80°C (PE-PBS80) as a food supplement to increase immune activities in a mice model. In this study, piglets were treated with 0.1%, 0.3%, and 0.5% PE-PBS80 for 3 wk after weaning. Experiments were performed at 2 separate farms using 2 different pig varieties. Composition of white blood cells, lymphocyte activation, and cytokine concentrations were analyzed to assess the immune modulation effect. In Exp. 1, the number of white blood cells increased significantly in the PE-PBS80 treatment and T- and B-cell activation increased as well (P piglets in all treatments in Exp. 2 were naturally infected by a rotavirus at the third day of the experiment but recovered after d 10. Increased lymphocyte activation was observed in the PE-PBS80 treatment (P piglets. Therefore, the PE-PBS80 pig placental extract, particularly the 0.3% supplement to the normal diet, could be useful as an alternative feed supplement to modulate immune activity during the early piglet period.

  10. Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.

    Directory of Open Access Journals (Sweden)

    Chaymae El Alaoui

    Full Text Available Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs. TTCCs play important roles in neuronal excitability, neuroprotection, sensory processes and sleep. These channels are also involved in epilepsy and pain. Using the whole-cell patch-clamp technique, we have characterized how Lavender and Rosemary extracts, as well as their major active compounds Linalool and Rosmarinic acid, modulate the electrophysiological properties of recombinant TTCCs (CaV3.2 expressed in HEK-293T cells. Both the methanolic and essential oil extracts as well as the active compounds of these plants inhibit Cav3.2 current in a concentration-dependent manner. In addition, these products also induce a negative shift of the steady-state inactivation of CaV3.2 current with no change in the activation properties. Taken together, our findings reveal that TTCCs are a molecular target of the Lavender and Rosemary compounds, suggesting that inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective effects of these plants.

  11. Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.

    Science.gov (United States)

    El Alaoui, Chaymae; Chemin, Jean; Fechtali, Taoufiq; Lory, Philippe

    2017-01-01

    Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs). TTCCs play important roles in neuronal excitability, neuroprotection, sensory processes and sleep. These channels are also involved in epilepsy and pain. Using the whole-cell patch-clamp technique, we have characterized how Lavender and Rosemary extracts, as well as their major active compounds Linalool and Rosmarinic acid, modulate the electrophysiological properties of recombinant TTCCs (CaV3.2) expressed in HEK-293T cells. Both the methanolic and essential oil extracts as well as the active compounds of these plants inhibit Cav3.2 current in a concentration-dependent manner. In addition, these products also induce a negative shift of the steady-state inactivation of CaV3.2 current with no change in the activation properties. Taken together, our findings reveal that TTCCs are a molecular target of the Lavender and Rosemary compounds, suggesting that inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective effects of these plants.

  12. Modulation of immune development and function by intestinal microbiota.

    Science.gov (United States)

    Kabat, Agnieszka M; Srinivasan, Naren; Maloy, Kevin J

    2014-11-01

    The immune system must constantly monitor the gastrointestinal tract for the presence of pathogens while tolerating trillions of commensal microbiota. It is clear that intestinal microbiota actively modulate the immune system to maintain a mutually beneficial relation, but the mechanisms that maintain homeostasis are not fully understood. Recent advances have begun to shed light on the cellular and molecular factors involved, revealing that a range of microbiota derivatives can influence host immune functions by targeting various cell types, including intestinal epithelial cells, mononuclear phagocytes, innate lymphoid cells, and B and T lymphocytes. Here, we review these findings, highlighting open questions and important challenges to overcome in translating this knowledge into new therapies for intestinal and systemic immune disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Experimental research of limits for thermal modulation transfer function

    Directory of Open Access Journals (Sweden)

    Tomić Ljubiša D.

    2009-01-01

    Full Text Available The paper presented testing of surface defects by pulse video thermography techniques. Such techniques rely on transient infrared radiation from the sample heated by the short duration flux initiated by flesh. Experimental measurements are realized by infrared sensor (FLIR camera. Testing results are considered for the samples with controlled designed defects beyond observed surfaces. The effects of response through the transparent wall are measured as infrared visible radiance. Researches with controlled samples are performed to verify visibility threshold of defect dimensions and forms, for possible use as modulation transfer function of defects hidden beyond the surfaces of thin metal walls. Dimensionless coefficients are derived for method estimations as the results from experimental research.

  14. Hepatocyte growth factor-modulated rat Leydig cell functions.

    Science.gov (United States)

    Del Bravo, Jessica; Catizone, Angela; Ricci, Giulia; Galdieri, Michela

    2007-01-01

    Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-Met and that HGF modulates germ cell proliferation and apoptosis. In the present article, we extend our study to the interstitial compartment of the testis and demonstrate that the c-Met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.

  15. The extraction of drug-disease correlations based on module distance in incomplete human interactome.

    Science.gov (United States)

    Yu, Liang; Wang, Bingbo; Ma, Xiaoke; Gao, Lin

    2016-12-23

    Extracting drug-disease correlations is crucial in unveiling disease mechanisms, as well as discovering new indications of available drugs, or drug repositioning. Both the interactome and the knowledge of disease-associated and drug-associated genes remain incomplete. We present a new method to predict the associations between drugs and diseases. Our method is based on a module distance, which is originally proposed to calculate distances between modules in incomplete human interactome. We first map all the disease genes and drug genes to a combined protein interaction network. Then based on the module distance, we calculate the distances between drug gene sets and disease gene sets, and take the distances as the relationships of drug-disease pairs. We also filter possible false positive drug-disease correlations by p-value. Finally, we validate the top-100 drug-disease associations related to six drugs in the predicted results. The overlapping between our predicted correlations with those reported in Comparative Toxicogenomics Database (CTD) and literatures, and their enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways demonstrate our approach can not only effectively identify new drug indications, but also provide new insight into drug-disease discovery.

  16. Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures.

    Science.gov (United States)

    Leone, Antonella; Lecci, Raffaella Marina; Durante, Miriana; Piraino, Stefano

    2013-05-22

    On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean "fried egg jellyfish" Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7 and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.

  17. Extracts of medicinal plants as functional beer additives

    Directory of Open Access Journals (Sweden)

    Đorđević Sofija

    2016-01-01

    Full Text Available This paper is based on determining the level of the antioxidant activity of beer, to which sensory acceptable amounts of selected extracts of medicinal plants were added, with the aim of obtaining a beer with increased functional and new sensory features. For purposes of this study a commercial lager beer type Pils and extracts of herbal drugs: Melissae folium, Thymi herba, Juniperi fructus, Urticae radix and Lupuli strobuli, were used. Total phenols were analyzed by the method of Folin-Ciocalteu, and the antioxidant activity of samples using FRAP and DPPH test. Sensory evaluation of beer was conducted on 80 subjects, using a nine levels hedonic scale. The results showed that the content of total phenols was the highest in the beer which thyme, juniper and lemon balm were added to (384.22, 365.38 and 363.08 mg GAE/L, respectively, representing the increase of 37.09, 30.36 and 29.55% (respectively compared to the commercial lager beer. Values of antioxidant activity were correlated with the content of total phenols. The extract of lemon balm blended in the best manner with the baseline, commercial lager beer in terms of sensory acceptability. New beer, enriched with lemon balm, had a pleasant, appealing and harmonious flavor and aroma.

  18. Intracellular modulation of NMDA receptor function by antipsychotic drugs.

    Science.gov (United States)

    Leveque, J C; Macías, W; Rajadhyaksha, A; Carlson, R R; Barczak, A; Kang, S; Li, X M; Coyle, J T; Huganir, R L; Heckers, S; Konradi, C

    2000-06-01

    The present study deals with the functional interaction of antipsychotic drugs and NMDA receptors. We show that both the conventional antipsychotic drug haloperidol and the atypical antipsychotic drug clozapine mediate gene expression via intracellular regulation of NMDA receptors, albeit to different extents. Data obtained in primary striatal culture demonstrate that the intraneuronal signal transduction pathway activated by haloperidol, the cAMP pathway, leads to phosphorylation of the NR1 subtype of the NMDA receptor at (897)Ser. Haloperidol treatment is likewise shown to increase (897)Ser-NR1 phosphorylation in rats in vivo. Mutation of (896)Ser and (897)Ser to alanine, which prevents phosphorylation at both sites, inhibits cAMP-mediated gene expression. We conclude that antipsychotic drugs have the ability to modulate NMDA receptor function by an intraneuronal signal transduction mechanism. This facilitation of NMDA activity is necessary for antipsychotic drug-mediated gene expression and may contribute to the therapeutic benefits as well as side effects of antipsychotic drug treatment.

  19. NAD+ Modulates p53 DNA Binding Specificity and Function

    Science.gov (United States)

    McLure, Kevin G.; Takagi, Masatoshi; Kastan, Michael B.

    2004-01-01

    DNA damage induces p53 DNA binding activity, which affects tumorigenesis, tumor responses to therapies, and the toxicities of cancer therapies (B. Vogelstein, D. Lane, and A. J. Levine, Nature 408:307-310, 2000; K. H. Vousden and X. Lu, Nat. Rev. Cancer 2:594-604, 2002). Both transcriptional and transcription-independent activities of p53 contribute to DNA damage-induced cell cycle arrest, apoptosis, and aneuploidy prevention (M. B. Kastan et al., Cell 71:587-597, 1992; K. H. Vousden and X. Lu, Nat. Rev. Cancer 2:594-604, 2002). Small-molecule manipulation of p53 DNA binding activity has been an elusive goal, but here we show that NAD+ binds to p53 tetramers, induces a conformational change, and modulates p53 DNA binding specificity in vitro. Niacinamide (vitamin B3) increases the rate of intracellular NAD+ synthesis, alters radiation-induced p53 DNA binding specificity, and modulates activation of a subset of p53 transcriptional targets. These effects are likely due to a direct effect of NAD+ on p53, as a molecule structurally related to part of NAD+, TDP, also inhibits p53 DNA binding, and the TDP precursor, thiamine (vitamin B1), inhibits intracellular p53 activity. Niacinamide and thiamine affect two p53-regulated cellular responses to ionizing radiation: rereplication and apoptosis. Thus, niacinamide and thiamine form a novel basis for the development of small molecules that affect p53 function in vivo, and these results suggest that changes in cellular energy metabolism may regulate p53. PMID:15509798

  20. Extracting Supersymmetry-Breaking Effects from Wave-Function Renormalization

    CERN Document Server

    Giudice, Gian Francesco

    1998-01-01

    We show that in theories in which supersymmetry breaking is communicated by renormalizable perturbative interactions, it is possible to extract the soft terms for the observable fields from wave-function renormalization. Therefore all the information about soft terms can be obtained from anomalous dimensions and beta functions, with no need to further compute any Feynman diagram. This method greatly simplifies calculations which are rather involved if performed in terms of component fields. For illustrative purposes we reproduce known results of theories with gauge-mediated supersymmetry breaking. We then use our method to obtain new results of phenomenological importance. We calculate the next-to-leading correction to the Higgs mass parameters, the two-loop soft terms induced by messenger-matter superpotential couplings, and the soft terms generated by messengers belonging to vector supermultiplets.

  1. Functionalized sio2 microspheres for extracting oil from produced water

    KAUST Repository

    Mishra, Himanshu

    2017-03-16

    Functionalized material, methods of producing the functionalized material, and use thereof for separation processes such as but not limited to use for separating and extracting a dissolved organic foulant, charged contaminant or oily matter or any combination thereof from water, such as produced water, are provided. In an embodiment, the functionalized material is a mineral material, such as mica, silica (e.g. an SiO2 microsphere) or a metal oxide, and the outer surface of the material is functionalized with an alkyl chain or a perfluorinated species. In an embodiment, the method of making the functionalized material, includes: a) providing a mineral material; b) providing an alkyl chain and/or a perfluorinated species, the alkyl chain or perfluorinated species selected to dissolve organic foulants, charged contaminants or oily matter from water or any combination thereof; c) hydroxylating the material via a concentrated acid solution or a basic solution; and d) grafting the alkyl chain and/or the perfluorinated species onto the material via a silanation reaction.

  2. A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1

    Directory of Open Access Journals (Sweden)

    Danyou Hu

    2017-01-01

    Full Text Available Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1 plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1.

  3. A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1

    Science.gov (United States)

    Hu, Danyou; Wang, Changming; Li, Fengxian; Su, Shulan; Yang, Niuniu; Yang, Yan; Zhu, Chan; Shi, Hao; Yu, Lei; Geng, Xiao; Gu, Leying; Yuan, Xiaolin; Wang, Zhongli

    2017-01-01

    Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM) exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI) mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1. PMID:28740739

  4. Quetiapine modulates functional connectivity in brain aggression networks.

    Science.gov (United States)

    Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

    2013-07-15

    Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Bacopa monnieri Extract (CDRI-08 Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

    Directory of Open Access Journals (Sweden)

    Papia Mondal

    2015-01-01

    Full Text Available Hepatic encephalopathy (HE, characterized by impaired cerebellar functions during chronic liver failure (CLF, involves N-methyl-D-aspartate receptor (NMDAR overactivation in the brain cells. Bacopa monnieri (BM extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B and its downstream mediators in cerebellum of rats with chronic liver failure (CLF, induced by administration of 50 mg/kg bw thioacetamide (TAA i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS- apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.

  6. Modulations in the biotransformation of tobacco extract and N'-nitrosonornicotine under differential dietary protein status.

    Science.gov (United States)

    Ammigan, N; Nair, U J; Amonkar, A J; Bhide, S V

    1989-01-01

    The modulation of the phase I and phase II biotransformation enzymes upon treatment with tobacco extract (TE) and N'-nitrosonornicotine (NNN) was investigated using male Sprague-Dawley rats fed differential protein diets. It was observed that the animals fed a low protein diet showed an overall decrease in the basal levels of hepatic and pulmonary phase I and II enzymes. TE and NNN significantly decreased the detoxifying system in the low-protein-fed animals. Animals fed 20% protein, however, showed significant increases in glutathione and glutathione S-transferase upon treatment. Furthermore, TE and NNN treatment brought about a significant depletion in the hepatic pool of vitamin A with a concomitant increase in the vitamin C levels.

  7. Dynamic identifying protein functional modules based on adaptive density modularity in protein-protein interaction networks.

    Science.gov (United States)

    Shen, Xianjun; Yi, Li; Yi, Yang; Yang, Jincai; He, Tingting; Hu, Xiaohua

    2015-01-01

    The identification of protein functional modules would be a great aid in furthering our knowledge of the principles of cellular organization. Most existing algorithms for identifying protein functional modules have a common defect -- once a protein node is assigned to a functional module, there is no chance to move the protein to the other functional modules during the follow-up processes, which lead the erroneous partitioning occurred at previous step to accumulate till to the end. In this paper, we design a new algorithm ADM (Adaptive Density Modularity) to detect protein functional modules based on adaptive density modularity. In ADM algorithm, according to the comparison between external closely associated degree and internal closely associated degree, the partitioning of a protein-protein interaction network into functional modules always evolves quickly to increase the density modularity of the network. The integration of density modularity into the new algorithm not only overcomes the drawback mentioned above, but also contributes to identifying protein functional modules more effectively. The experimental result reveals that the performance of ADM algorithm is superior to many state-of-the-art protein functional modules detection techniques in aspect of the accuracy of prediction. Moreover, the identified protein functional modules are statistically significant in terms of "Biological Process" annotated in Gene Ontology, which provides substantial support for revealing the principles of cellular organization.

  8. Measurement of the frequency modulation transfer function of a laser using a Mach Zehnder interferometer

    Science.gov (United States)

    McRae, T. G.; Field, B. J.; Manson, P. J.

    2005-06-01

    A technique is presented for determining the frequency modulation transfer function of a laser. The method is based on a Mach Zehnder interferometer, with a significant difference in the optical path lengths of the two arms. A frequency-modulated laser beam incident on the interferometer produces a phase-modulated photocurrent signal with an effective modulation index that is related to the amplitude of the optical frequency modulation. Techniques for determining both the amplitude and the phase of the optical frequency modulation from the photocurrent signal are described.

  9. Modulation Transfer Function of Infrared Focal Plane Arrays

    Science.gov (United States)

    Gunapala, S. D.; Rafol, S. B.; Ting, D. Z.; Soibel, A.; Hill, C. J.; Khoshakhlagh, A.; Liu, J. K.; Mumolo, J. M.; Hoglund, L.; Luong, E. M.

    2015-01-01

    Modulation transfer function (MTF) is the ability of an imaging system to faithfully image a given object. The MTF of an imaging system quantifies the ability of the system to resolve or transfer spatial frequencies. In this presentation we will discuss the detail MTF measurements of 1024x1024 pixels mid -wavelength and long- wavelength quantum well infrared photodetector, and 320x256 pixels long- wavelength InAs/GaSb superlattice infrared focal plane arrays (FPAs). Long wavelength Complementary Barrier Infrared Detector (CBIRD) based on InAs/GaSb superlattice material is hybridized to recently designed and fabricated 320x256 pixel format ROIC. The n-type CBIRD was characterized in terms of performance and thermal stability. The experimentally measured NE delta T of the 8.8 micron cutoff n-CBIRD FPA was 18.6 mK with 300 K background and f/2 cold stop at 78K FPA operating temperature. The horizontal and vertical MTFs of this pixel fully delineated CBIRD FPA at Nyquist frequency are 49% and 52%, respectively.

  10. A product of heme catabolism modulates bacterial function and survival.

    Directory of Open Access Journals (Sweden)

    Christopher L Nobles

    Full Text Available Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC, a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome and Gram-positive bacteria being susceptible to membrane disruption (negative outcome. This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.

  11. DNA topoisomerase II modulates insulator function in Drosophila.

    Directory of Open Access Journals (Sweden)

    Edward Ramos

    2011-01-01

    Full Text Available Insulators are DNA sequences thought to be important for the establishment and maintenance of cell-type specific nuclear architecture. In Drosophila there are several classes of insulators that appear to have unique roles in gene expression. The mechanisms involved in determining and regulating the specific roles of these insulator classes are not understood. Here we report that DNA Topoisomerase II modulates the activity of the Su(Hw insulator. Downregulation of Topo II by RNAi or mutations in the Top2 gene result in disruption of Su(Hw insulator function. This effect is mediated by the Mod(mdg42.2 protein, which is a unique component of the Su(Hw insulator complex. Co-immunoprecipitation and yeast two-hybrid experiments show that Topo II and Mod(mdg42.2 proteins directly interact. In addition, mutations in Top2 cause a slight decrease of Mod(mdg42.2 transcript but have a dramatic effect on Mod(mdg42.2 protein levels. In the presence of proteasome inhibitors, normal levels of Mod(mdg42.2 protein and its binding to polytene chromosomes are restored. Thus, Topo II is required to prevent Mod(mdg42.2 degradation and, consequently, to stabilize Su(Hw insulator-mediated chromatin organization.

  12. DNA Topoisomerase II Modulates Insulator Function in Drosophila

    Science.gov (United States)

    Ramos, Edward; Torre, Eduardo A.; Bushey, Ashley M.; Gurudatta, B. V.; Corces, Victor G.

    2011-01-01

    Insulators are DNA sequences thought to be important for the establishment and maintenance of cell-type specific nuclear architecture. In Drosophila there are several classes of insulators that appear to have unique roles in gene expression. The mechanisms involved in determining and regulating the specific roles of these insulator classes are not understood. Here we report that DNA Topoisomerase II modulates the activity of the Su(Hw) insulator. Downregulation of Topo II by RNAi or mutations in the Top2 gene result in disruption of Su(Hw) insulator function. This effect is mediated by the Mod(mdg4)2.2 protein, which is a unique component of the Su(Hw) insulator complex. Co-immunoprecipitation and yeast two-hybrid experiments show that Topo II and Mod(mdg4)2.2 proteins directly interact. In addition, mutations in Top2 cause a slight decrease of Mod(mdg4)2.2 transcript but have a dramatic effect on Mod(mdg4)2.2 protein levels. In the presence of proteasome inhibitors, normal levels of Mod(mdg4)2.2 protein and its binding to polytene chromosomes are restored. Thus, Topo II is required to prevent Mod(mdg4)2.2 degradation and, consequently, to stabilize Su(Hw) insulator-mediated chromatin organization. PMID:21304601

  13. Disease association and inter-connectivity analysis of human brain specific co-expressed functional modules.

    Science.gov (United States)

    Oh, Kimin; Hwang, Taeho; Cha, Kihoon; Yi, Gwan-Su

    2015-12-16

    In the recent studies, it is suggested that the analysis of transcriptomic change of functional modules instead of individual genes would be more effective for system-wide identification of cellular functions. This could also provide a new possibility for the better understanding of difference between human and chimpanzee. In this study, we analyzed to find molecular characteristics of human brain functions from the difference of transcriptome between human and chimpanzee's brain using the functional module-centric co-expression analysis. We performed analysis of brain disease association and systems-level connectivity of species-specific co-expressed functional modules. Throughout the analyses, we found human-specific functional modules and significant overlap between their genes in known brain disease genes, suggesting that human brain disorder could be mediated by the perturbation of modular activities emerged in human brain specialization. In addition, the human-specific modules having neurobiological functions exhibited higher networking than other functional modules. This finding suggests that the expression of neural functions are more connected than other functions, and the resulting high-order brain functions could be identified as a result of consolidated inter-modular gene activities. Our result also showed that the functional module based transcriptome analysis has a potential to expand molecular understanding of high-order complex functions like cognitive abilities and brain disorders.

  14. Estimated Green's function extracted from superconducting gravimeters and seismometers

    Science.gov (United States)

    Zeng, Xiangfang; Zhan, Zhongwen; Zheng, Yong

    2011-04-01

    Estimated Green's function (EGF) between stations has been extracted from ambient seismic noise, direct surface wave and coda waves. It is also confirmed by laboratory experiments on ultrasonics and theoretical derivations assuming diffusive wave field, equi-partition of modes or random sources on an enclosed surface. This method provides a new approach to study the crust and mantle structure at regional scale, continental scale and global scale. Following the achievements with seismometer records, the records of infrasonic station, hydrophone and microphone were also used to obtain the EGFs of different wave fields. Since superconducting gravimeter is a better long period instrument than regular seismometer, EGF at longer period is expected to be obtained with the cross correlation of gravity data. In this paper, we will show the EGFs extracted by cross-correlations between the superconducting gravimeters and the seismometers. Both the travel times and dispersion curves obtained from different data types are consistent. The result shows that it is possible to retrieve the deep structure by the cross correlation of gravity data.

  15. Physicochemical and functional properties of gelatin extracted from Yak skin.

    Science.gov (United States)

    Xu, Mengqi; Wei, Lixin; Xiao, Yuancan; Bi, Hongtao; Yang, Hongxia; Du, Yuzhi

    2017-02-01

    Different molecular weight distribution (MWD) gelatin was extracted from Yak skin after enzymatic pretreatments and their physicochemical and functional properties (SDS-PAGE, UV-vis absorption spectra, DSC, FT-IR, Amino acid analysis, AFM, emulsibility and foamability) were analyzed. The gelatin was extracted by pepsin and got different MWD of Yak skin gelatin by controlling the enzymolysis time. The SDS-PAGE showed the MWD of the Yak skin gelatin. The UV-vis absorption turned out that the broad MWD of Yak skin gelatin had a higher maximum absorption peaks. The FT-IR and AFM indicated that the gelatin structures and microstructures changed with the change of the MWD. The broad MWD of the Yak skin gelatin had a higher denaturation temperature (TD), and it was higher than most of the other mammals and marine biological gelatin. The broad MWD gelatin also had higher imino acids (proline and hydroxyproline) contents and lower foamability and emulsibility compared to the narrow MWD gelatin. These findings, obtained for the first time for Yak skin gelatin, showed that it has great potential for application as an alternative to commercial gelatin due to its good thermotolerance, particularly in the applications of the biological materials, stabilizer of thermo-tolerant and so on. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Extraction of functional ingredients from spinach (Spinacia oleracea L.) using liquid solvent and supercritical CO₂ extraction.

    Science.gov (United States)

    Jaime, Laura; Vázquez, Erika; Fornari, Tiziana; López-Hazas, María del Carmen; García-Risco, Mónica R; Santoyo, Susana; Reglero, Guillermo

    2015-03-15

    In this work three different techniques were applied to extract dry leaves of spinach (Spinacia oleracea): solid-liquid extraction (SLE), pressurised liquid extraction (PLE) and supercritical fluid extraction (SFE) to investigate the influence of extraction solvent and technique on extracts composition and antioxidant activity. Moreover, the influence of carotenoids and phenolic compounds on the antioxidant and anti-inflammatory activities of spinach extracts was also studied. The higher concentrations of carotenoids and the lower content of phenolic compounds were observed in the supercritical CO₂ extracts; whereas water and/or ethanol PLE extracts presented low amounts of carotenoids and the higher concentrations of phenolic compounds. PLE extract with the highest content of phenolic compounds showed the highest antioxidant activity, although SFE carotenoid rich extract also showed a high antioxidant activity. Moreover, both extracts presented an important anti-inflammatory activity. PLE seems to be a good technique for the extraction of antioxidant and anti-inflammatory compounds from spinach leaves. Moreover, spinach phenolic compounds and carotenoids present a high antioxidant activity, whereas spinach carotenoids seem to show a higher anti-inflammatory activity than phenolic compounds. It is worth noting that of our knowledge this is the first time the anti-inflammatory activity of lipophilic extracts from spinach leaves is reported. © 2014 Society of Chemical Industry.

  17. Temporal modulation transfer functions in cochlear implantees using a method that limits overall loudness cues

    Science.gov (United States)

    Fraser, Matthew; McKay, Colette M.

    2012-01-01

    Temporal modulation transfer functions (TMTFs) were measured for six users of cochlear implants, using different carrier rates and levels. Unlike most previous studies investigating modulation detection, the experimental design limited potential effects of overall loudness cues. Psychometric functions (percent correct discrimination of modulated from unmodulated stimuli versus modulation depth) were obtained. For each modulation depth, each modulated stimulus was loudness balanced to the unmodulated reference stimulus, and level jitter was applied in the discrimination task. The loudness-balance data showed that the modulated stimuli were louder than the unmodulated reference stimuli with the same average current, thus confirming the need to limit loudness cues when measuring modulation detection. TMTFs measured in this way had a low-pass characteristic, with a cut-off frequency (at comfortably loud levels) similar to that for normal-hearing listeners. A reduction in level caused degradation in modulation detection efficiency and a lower-cut-off frequency (i.e. poorer temporal resolution). An increase in carrier rate also led to a degradation in modulation detection efficiency, but only at lower levels or higher modulation frequencies. When detection thresholds were expressed as a proportion of dynamic range, there was no effect of carrier rate for the lowest modulation frequency (50 Hz) at either level. PMID:22146425

  18. Improving functional modules discovery by enriching interaction networks with gene profiles

    KAUST Repository

    Salem, Saeed

    2013-05-01

    Recent advances in proteomic and transcriptomic technologies resulted in the accumulation of vast amount of high-throughput data that span multiple biological processes and characteristics in different organisms. Much of the data come in the form of interaction networks and mRNA expression arrays. An important task in systems biology is functional modules discovery where the goal is to uncover well-connected sub-networks (modules). These discovered modules help to unravel the underlying mechanisms of the observed biological processes. While most of the existing module discovery methods use only the interaction data, in this work we propose, CLARM, which discovers biological modules by incorporating gene profiles data with protein-protein interaction networks. We demonstrate the effectiveness of CLARM on Yeast and Human interaction datasets, and gene expression and molecular function profiles. Experiments on these real datasets show that the CLARM approach is competitive to well established functional module discovery methods.

  19. Extract of Lillium candidum L. Can Modulate the Genotoxicity of the Antibiotic Zeocin

    Directory of Open Access Journals (Sweden)

    Peter Bryant

    2011-12-01

    Full Text Available Lilium candidum L. extract (LE is well known in folk medicine for the treatment of burns, ulcers, inflammations and for healing wounds. This work aims to clarify whether the genotoxic potential of the radiomimetic antibiotic zeocin (Zeo could be modulated by LE. Our results indicate that LE exerts no cytotoxic, DNA-damaging and clastogenic activity in in Chlamydomonas reinhardtii, Pisum sativum L. and Hordeum vulgare L. test systems over a broad concentration range. Weak but statistically significant clastogenic effects due to the induction of micronuclei and chromosome aberrations have been observed in H. vulgare L. after treatment with 200 and 300 μg/mL LE. To discriminate protective from adverse action of LE different experimental designs have been used. Our results demonstrate that the treatment with mixtures of LE and Zeo causes an increase in the level of DNA damage, micronuclei and “metaphases with chromatid aberrations” (MwA. Clear evidence has been also obtained indicating that pretreatment with LE given 4 h before the treatment with Zeo accelerates the rejoining kinetics of Zeo-induced DNA damage in P. sativum L. and C. reinhardtii, and can decrease clastogenic effect of Zeo measured as frequencies of micronuclei and MwA in H. vulgare L. Here, we show for the first time that LE can modulate the genotoxic effects of zeocin. The molecular mode of action strongly depends on the experimental design and varies from synergistic to protective effect (adaptive response–AR. Our results also revealed that LE-induced AR to zeocin involves up-regulation of DSB rejoining in C. reinhardtii and P. sativum L. cells.

  20. Radix Puerariae modulates glutamatergic synaptic architecture and potentiates functional synaptic plasticity in primary hippocampal neurons.

    Science.gov (United States)

    Bhuiyan, Mohammad Maqueshudul Haque; Haque, Md Nazmul; Mohibbullah, Md; Kim, Yung Kyu; Moon, Il Soo

    2017-09-14

    Neurologic disorders are frequently characterized by synaptic pathology, including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Therefore, to promote and/or protect synapses by the use of natural molecules capable of modulating neurodevelopmental events, such as, spinogenesis and synaptic plasticity, could offer a preventive and curative strategy for nervous disorders associated with synaptic pathology. Radix Puerariae, the root of Pueraria monatana var. lobata (Willd.) Sanjappa&Pradeep, is a Chinese ethnomedicine, traditionally used for the treatment of memory-related nervous disorders including Alzheimer's disease. In the previous study, we showed that the ethanolic extracts of Radix Puerariae (RPE) and its prime constituent, puerarin induced neuritogenesis and synapse formation in cultured hippocampal neurons, and thus could improve memory functions. In the present study, we specifically investigated the abilities of RPE and puerarin to improve memory-related brain disorders through modulating synaptic maturation and functional potentiation. Rat embryonic (E19) brain neurons were cultured in the absence or presence of RPE or puerarin. At predetermined times, cells were live-stained with DiO or fixed and immunostained to visualize neuronal morphologies, or lysed for protein harvesting. Morphometric analyses of dendritic spines and synaptogenesis were performed using Image J software. Functional pre- and postsynaptic plasticity was measured by FM1-43 staining and whole-cell patch clamping, respectively. RPE or puerarin-mediated changes in actin-related protein 2 were assessed by Western blotting. Neuronal survivals were measured using propidium iodide exclusion assay. RPE and puerarin both: (1) promoted a significant increase in the numbers, and maturation, of dendritic spines; (2) modulated the formation of glutamatergic synapses; (3) potentiated synaptic transmission by increasing the sizes of

  1. A novel subgradient-based optimization algorithm for blockmodel functional module identification.

    Science.gov (United States)

    Wang, Yijie; Qian, Xiaoning

    2013-01-01

    Functional module identification in biological networks may provide new insights into the complex interactions among biomolecules for a better understanding of cellular functional organization. Most of existing functional module identification methods are based on the optimization of network modularity and cluster networks into groups of nodes within which there are a higher-than-expectation number of edges. However, module identification simply based on this topological criterion may not discover certain kinds of biologically meaningful modules within which nodes are sparsely connected but have similar interaction patterns with the rest of the network. In order to unearth more biologically meaningful functional modules, we propose a novel efficient convex programming algorithm based on the subgradient method with heuristic path generation to solve the problem in a recently proposed framework of blockmodel module identification. We have implemented our algorithm for large-scale protein-protein interaction (PPI) networks, including Saccharomyces cerevisia and Homo sapien PPI networks collected from the Database of Interaction Proteins (DIP) and Human Protein Reference Database (HPRD). Our experimental results have shown that our algorithm achieves comparable network clustering performance in comparison to the more time-consuming simulated annealing (SA) optimization. Furthermore, preliminary results for identifying fine-grained functional modules in both biological networks and the comparison with the commonly adopted Markov Clustering (MCL) algorithm have demonstrated the potential of our algorithm to discover new types of modules, within which proteins are sparsely connected but with significantly enriched biological functionalities.

  2. Modulation by Polypodium leucotomos extract of cytokine patterns in experimental trichomoniasis model

    Directory of Open Access Journals (Sweden)

    Nogal-Ruiz J.J.

    2003-03-01

    Full Text Available The immunomodulating effects of Anapsos®, an aqueous hydrosoluble extract obtained from the rhizomes of the fern Polypodium leucotomos, on both pathogenicity and cytokine levels in serum (IFN-γ/IL-4 were assayed in a Trichomonas vaginalis experimental model (BALB/c mice infected with 107 trichomonads and examined at day 15 after infection. Doses of 20 mg/kg/day administered for 10 days before the infection with the parasite induced a decrease of the experimental pathogenicity approximately 10-20 % compared to controls. Gross histopathologic changes at abdominal organs and mortality rate, as a consequence of pathogenicity of the protozoa and the immune response of the host, were evaluated. IFN-y and IL-4 cytokines were determined on days -5, 0, 5, 10, and 15 postinfection by indirect ELISA. Treatment with PAL before infection modulates and downregulates the IFN-γ concentration, while anticipates and upregulates the IL-4 level. The assays performed have showed the utility of the murine model of experimental trichomoniasis for the evaluation of immunomodulatory activity of synthetic or natural products.

  3. Dynamic range of frontoparietal functional modulation is associated with working memory capacity limitations in older adults.

    Science.gov (United States)

    Hakun, Jonathan G; Johnson, Nathan F

    2017-11-01

    Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60-77years of age), age was negatively associated with frontoparietal modulation range. Individuals with greater modulation range exhibited more accurate N-Back performance. In addition, despite a lack of significant relationships between N-Back and complex span task performance, range of frontoparietal modulation during the N-Back significantly predicted domain-general estimates of WM capacity. Consistent with previous cross-sectional findings, older individuals with less modulation range exhibited greater activation at the lowest level of task difficulty but less activation at the highest levels of task difficulty. Our results are largely consistent with existing theories of neurocognitive aging (e.g. CRUNCH) but focus attention on dynamic range of functional modulation asa novel marker of WM capacity-limitations in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Fungal infection control by garlic extracts (Allium sativum L. and modulation of peritoneal macrophages activity in murine model of sporotrichosis

    Directory of Open Access Journals (Sweden)

    J. P. Burian

    2017-05-01

    Full Text Available Abstract Garlic (Allium sativum L. is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America, is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines’ production (IL-1β, IL-10 and IL-12 and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.

  5. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    Science.gov (United States)

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

  6. Modulating gene function with peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E.; Crooke, Stanley T.

    2008-01-01

    A review on peptide nucleic acid (PNA) oligomers as modulators of gene expression ranging from gene silencing at the mRNAor the dsDNA (antigene) level, and redirection of mRNA splicing to gene activation through transcription bubble mimicking. PNA chem., anti-infective agents, cellular delivery, ......, and in vivo bioavailability of PNA are briefly discussed. [on SciFinder (R)]...

  7. New Y-function based MOSFET parameter extraction method from weak to strong inversion range

    Science.gov (United States)

    Henry, J. B.; Rafhay, Q.; Cros, A.; Ghibaudo, G.

    2016-09-01

    A new Y-function based MOSFET parameter extraction method is proposed. This method relies on explicit expressions of inversion charge and drain current versus Yc(=Qi√Cgc)-function and Y(=Id/√gm)-function, respectively, applicable from weak to strong inversion range. It enables a robust MOSFET parameter extraction even for low gate voltage overdrive, whereas conventional extraction techniques relying on strong inversion approximation fail.

  8. Temporal modulation transfer functions measured from auditory-nerve responses following sensorineural hearing loss.

    Science.gov (United States)

    Kale, Sushrut; Heinz, Michael G

    2012-04-01

    The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as characterized by temporal modulation transfer functions (TMTFs), generally shows a low-pass shape with a cut-off frequency that increases with fiber characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this result has been interpreted to suggest that peripheral filtering has a significant effect on limiting the encoding of higher modulation frequencies. Sensorineural hearing loss (SNHL), which is typically associated with broadened tuning, is thus predicted to increase the range of modulation frequencies encoded; however, perceptual studies have generally not supported this prediction. The present study sought to determine whether the range of modulation frequencies encoded by AN fibers is affected by SNHL, and whether the effects of SNHL on envelope coding are similar at all modulation frequencies within the TMTF passband. Modulation response gain for sinusoidally amplitude modulated (SAM) tones was measured as a function of modulation frequency, with the carrier frequency placed at fiber CF. TMTFs were compared between normal-hearing chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers had significantly broadened tuning. Synchrony and phase responses for individual SAM tone components were quantified to explore a variety of factors that can influence modulation coding. Modulation gain was found to be higher than normal in noise-exposed fibers across the entire range of modulation frequencies encoded by AN fibers. The range of modulation frequencies encoded by noise-exposed AN fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off frequencies. These results suggest that physiological factors other than peripheral filtering may have a significant role in determining the range of modulation frequencies encoded in AN fibers. Furthermore, these neural data may help to explain the lack of a consistent association

  9. Temporal Modulation Transfer Functions Measured From Auditory-Nerve Responses Following Sensorineural Hearing Loss

    Science.gov (United States)

    Kale, Sushrut; Heinz, Michael G.

    2012-01-01

    The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as characterized by temporal modulation transfer functions (TMTFs), generally shows a low-pass shape with a cut-off frequency that increases with fiber characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this result has been interpreted to suggest that peripheral filtering has a significant effect on limiting the encoding of higher modulation frequencies. Sensorineural hearing loss (SNHL), which is typically associated with broadened tuning, is thus predicted to increase the range of modulation frequencies encoded; however, perceptual studies have generally not supported this prediction. The present study sought to determine whether the range of modulation frequencies encoded by AN fibers is affected by SNHL, and whether the effects of SNHL on envelope coding are similar at all modulation frequencies within the TMTF passband. Modulation response gain for sinusoidally amplitude modulated (SAM) tones was measured as a function of modulation frequency, with the carrier frequency placed at fiber CF. TMTFs were compared between normal-hearing chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers had significantly broadened tuning. Synchrony and phase responses for individual SAM-tone components were quantified to explore a variety of factors that can influence modulation coding. Modulation gain was found to be higher than normal in noise-exposed fibers across the entire range of modulation frequencies encoded by AN fibers. The range of modulation frequencies encoded by noise-exposed AN fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off frequencies. These results suggest that physiological factors other than peripheral filtering may have a significant role in determining the range of modulation frequencies encoded in AN fibers. Furthermore, these neural data may help to explain the lack of a consistent association

  10. Modulating functions method for parameters estimation in the fifth order KdV equation

    KAUST Repository

    Asiri, Sharefa M.

    2017-07-25

    In this work, the modulating functions method is proposed for estimating coefficients in higher-order nonlinear partial differential equation which is the fifth order Kortewegde Vries (KdV) equation. The proposed method transforms the problem into a system of linear algebraic equations of the unknowns. The statistical properties of the modulating functions solution are described in this paper. In addition, guidelines for choosing the number of modulating functions, which is an important design parameter, are provided. The effectiveness and robustness of the proposed method are shown through numerical simulations in both noise-free and noisy cases.

  11. Modulation of jejunal contractions by extract of Carica papaya L. seeds.

    Science.gov (United States)

    Adebiyi, Adebowale; Adaikan, P Ganesan

    2005-07-01

    Carica papaya L. (papaya) seed preparations are used in traditional medicine to expel intestinal worms in human and ruminants. In the present study, an ethanol extract of papaya seeds (EEPS; 0.1-6.4 mg/mL) caused concentration-dependent inhibition of jejunal contractions in contrast to corresponding concentrations of DMSO (solvent control). The inhibitory effect of EEPS on jejunal contractions was significantly irreversible. Previous studies have indicated that benzyl isothiocyanate (BITC) is the main bioactive compound responsible for the anthelmintic activity of papaya seeds. In the present study, standard BITC (0.01-0.64 mmol/L) also caused significant irreversible inhibition of jejunal contractions. Recovery of jejunal contractions after BITC-induced inhibition was weaker than recovery after EEPS-induced inhibition (BITC versus EEPS: 19 +/- 7% vs 38 +/- 13%). Cryosections of the jejunum showed marked morphological damage of the segments treated with BITC in contrast to DMSO-treated segments. EEPS-induced jejunal damage was, however, less marked. These results indicate that papaya seed extract and BITC, its principal bioactive constituent are capable of weakening the contractile capability of rabbit isolated jejunum. It is thus envisaged that at the toxic level that will be needed to kill and expel intestinal worms in vivo, BITC may also cause impairment of intestinal functions.

  12. Modulation functions of incommensurately modulated Cr2P2O7 studied by the maximum entropy method (MEM).

    Science.gov (United States)

    Li, Liang; Schönleber, Andreas; van Smaalen, Sander

    2010-04-01

    The maximum entropy method (MEM) has been used to determine electron density in superspace of incommensurately modulated chromium pyrophosphate from X-ray diffraction data measured by Palatinus et al. [(2006), Acta Cryst. B62, 556-566]. Chromium pyrophosphate, Cr(2)P(2)O(7), contains ordered regions (83% of the volume) and regions with disorder. Analysis of the MEM density has allowed the determination of the displacive modulation functions within ordered regions. The disordered regions can be described as the alternate occupation of two conformations of the pyrophosphate group and two positions of the chromium atom, with occupational probabilities that depend continuously on the phase of modulation t. A structure model based on the interpretation of the MEM density provides a fit to the diffraction data of the same quality as the model given by Palatinus et al. (2006). The failure to find a model that better fits the data is attributed to the intrinsic inaccuracy of approximately 0.01 A for positions derived from the MEM and to the difficulties in constructing an appropriate model for the anharmonic ADPs and their modulation functions from electron densities.

  13. Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways.

    Science.gov (United States)

    Hsu, Hsien-Yeh; Hua, Kuo-Feng; Lin, Chun-Cheng; Lin, Chun-Hung; Hsu, Jason; Wong, Chi-Huey

    2004-11-15

    We have demonstrated that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells. Interestingly, via responding to LPS in genetic variation of murine macrophage HeNC2 and GG2EE cell lines, and using TLR4 Ab blockage in human blood-derived monocytic macrophages, we have found that the TLR4, but not complement receptor type 3, is a putative receptor of EORP, mediating the consequent immunomodulating events associated with IL-1 gene expression. Based on our studies of reactive oxygen species production, polymyxin B inhibition, and protein tyrosine kinase (PTK) activity, we ruled out the possibility of LPS contamination in EORP. We have found that EORP differentially modulates the protein kinase (PK)-mediated signal transduction pathways associated with inflammatory cytokine IL-1. In human macrophages and murine macrophage J774A.1 cells, EORP was found to up-regulate IL-1 secretion and pro-IL-1 (precursor of IL-1) as well as IL-1-converting enzyme expression. Specifically, EORP rapidly stimulates PTK-mediated phosphorylation, followed by induction of PKs and activation of MAPKs: ERK, JNK, and p38. Using PK inhibitors in the kinase activity assays, Western blot analyses and IL-1 ELISA, we have extensively examined and dissected the role of individual PK in the regulation of pro-IL-1/IL-1. Our findings establish that EORP-mediated signaling pathways are involved in the pro-IL-1/IL-1 regulation: PTK/protein kinase C/MEK1/ERK and PTK/Rac1/p21-activated kinase/p38.

  14. Opposite modulation of brain functional networks implicated at low vs. high demand of attention and working memory.

    Directory of Open Access Journals (Sweden)

    Jiansong Xu

    Full Text Available Functional magnetic resonance imaging (fMRI studies indicate that the brain organizes its activity into multiple functional networks (FNs during either resting condition or task-performance. However, the functions of these FNs are not fully understood yet.To investigate the operation of these FNs, spatial independent component analysis (sICA was used to extract FNs from fMRI data acquired from healthy participants performing a visual task with two levels of attention and working memory load. The task-related modulations of extracted FNs were assessed. A group of FNs showed increased activity at low-load conditions and reduced activity at high-load conditions. These FNs together involve the left lateral frontoparietal cortex, insula, and ventromedial prefrontal cortex. A second group of FNs showed increased activity at high-load conditions and reduced activity at low-load conditions. These FNs together involve the intraparietal sulcus, frontal eye field, lateral frontoparietal cortex, insula, and dorsal anterior cingulate, bilaterally. Though the two groups of FNs showed opposite task-related modulations, they overlapped extensively at both the lateral and medial frontoparietal cortex and insula. Such an overlap of FNs would not likely be revealed using standard general-linear-model-based analyses.By assessing task-related modulations, this study differentiated the functional roles of overlapping FNs. Several FNs including the left frontoparietal network are implicated in task conditions of low attentional load, while another set of FNs including the dorsal attentional network is implicated in task conditions involving high attentional demands.

  15. Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells.

    Science.gov (United States)

    Sharma, M; Arnason, J T; Burt, A; Hudson, J B

    2006-02-01

    Extracts of Echinacea purpurea are among the most widely used herbal medicines throughout Europe and North America for the prevention or treatment of common cold, coughs, bronchitis and other upper respiratory infections. Popular preparations include expressed juice from the aerial parts of the plant (which contain polysaccharides) and alcoholic tinctures from roots (containing caffeic acid derivatives and alkylamides). Since immune modulation has been reported for similar extracts, cytokine antibody arrays were used to investigate the changes in the pro-inflammatory cytokines and chemokines released from a cultured line of human bronchial epithelial cells exposed to Rhinovirus 14 and two different chemically characterized Echinacea extracts. Virus infection stimulated the release of at least 31 cytokine-related molecules, including several important chemokines known to attract inflammatory cells. Most of these effects were reversed by simultaneous exposure to either of the two Echinacea extracts, although the patterns of response were different for the two extracts. These results could explain the antiinflammatory properties of Echinacea extracts. Furthermore, a number of these cytokines were stimulated by the same Echinacea preparations in uninfected cells. These observations therefore provide support for the alleged beneficial uses of Echinacea extracts. Copyright 2006 John Wiley & Sons, Ltd.

  16. Bioactive phytochemicals in wheat: Extraction, analysis, processing, and functional properties

    Science.gov (United States)

    Whole wheat provides a rich source of bioactive phytochemicals namely, phenolic acids, carotenoids, tocopherols, alkylresorcinols, arabinoxylans, benzoxazinoids, phytosterols, and lignans. This review provides information on the distribution, extractability, analysis, and nutraceutical properties of...

  17. Modulation of immune function by a modified bovine whey protein concentrate

    National Research Council Canada - National Science Library

    Cross, M L; Gill, H S

    1999-01-01

    .... In the present report, a modified whey protein concentrate (mWPC), derived as a by-product from the commercial manufacture of cheese, was tested for its ability to modulate murine immune function in vitro...

  18. Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions.

    Directory of Open Access Journals (Sweden)

    Yuval Ramot

    Full Text Available BACKGROUND: Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown. METHODS AND FINDINGS: We have studied the effects of the prototypic polyamine, spermidine (0.1-1 µM, on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth (anagen. Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase (ODC, downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S/G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration (POP3, or endoplasmic reticulum and mitochondrial functions (SYVN1, NACA and SLC25A3. Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF's companion layer in situ. CONCLUSIONS: These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology.

  19. Multi-function Mach-Zehnder modulator for pulse shaping and generation.

    Science.gov (United States)

    Gao, Jing; Wu, Hui

    2016-09-19

    We present a multi-function electronic-photonic integrated circuit (EPIC) design which exploits a new operation mode of a Mach-Zehnder modulator (MZM). Different from the conventional design, the two arms of the modulator are driven by time-shifted signals of tunable amplitude. We study its operation in the linear and quadratic regions where the MZM is biased at π/2 and π initial phase difference, respectively. In the linear region, the modulator sums the waveforms of the driving signals in the two arms, which can be used to add pre-emphasis function to the modulator, and hence it obviates an electrical pre-emphasis driver. Furthermore, when operating in the quadratic region, the modulator can produce optical pulses with tunable pulse width at double clock rate. Prototype circuits are designed first using a suit of device, electromagnetic simulators to build compact models, and then importing into a photonic circuit simulator for complete circuit performance evaluation.

  20. Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking-Dependent and Crosslinking-Independent Functions.

    Science.gov (United States)

    Steppan, Jochen; Bergman, Yehudit; Viegas, Kayla; Armstrong, Dinani; Tan, Siqi; Wang, Huilei; Melucci, Sean; Hori, Daijiro; Park, Sung Yong; Barreto, Sebastian F; Isak, Abraham; Jandu, Sandeep; Flavahan, Nicholas; Butlin, Mark; An, Steven S; Avolio, Alberto; Berkowitz, Dan E; Halushka, Marc K; Santhanam, Lakshmi

    2017-02-03

    The structural elements of the vascular wall, namely, extracellular matrix and smooth muscle cells (SMCs), contribute to the overall stiffness of the vessel. In this study, we examined the crosslinking-dependent and crosslinking-independent roles of tissue transglutaminase (TG2) in vascular function and stiffness. SMCs were isolated from the aortae of TG2-/- and wild-type (WT) mice. Cell adhesion was examined by using electrical cell-substrate impedance sensing and PicoGreen assay. Cell motility was examined using a Boyden chamber assay. Cell proliferation was examined by electrical cell-substrate impedance sensing and EdU incorporation assays. Cell micromechanics were studied using magnetic torsion cytometry and spontaneous nanobead tracer motions. Aortic mechanics were examined by tensile testing. Vasoreactivity was studied by wire myography. SMCs from TG2-/- mice had delayed adhesion, reduced motility, and accelerated de-adhesion and proliferation rates compared with those from WT. TG2-/- SMCs were stiffer and displayed fewer cytoskeletal remodeling events than WT. Collagen assembly was delayed in TG2-/- SMCs and recovered with adenoviral transduction of TG2. Aortic rings from TG2-/- mice were less stiff than those from WT; stiffness was partly recovered by incubation with guinea pig liver TG2 independent of crosslinking function. TG2-/- rings showed augmented response to phenylephrine-mediated vasoconstriction when compared with WT. In human coronary arteries, vascular media and plaque, high abundance of fibronectin expression, and colocalization with TG2 were observed. TG2 modulates vascular function/tone by altering SMC contractility independent of its crosslinking function and contributes to vascular stiffness by regulating SMC proliferation and matrix remodeling. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Identifying similar functional modules by a new hybrid spectral clustering method.

    Science.gov (United States)

    Madani, S; Faez, K; Aminghafari, M

    2012-10-01

    Recently, a large number of researches have focused on finding cellular modules within protein-protein interaction networks. Until now, most of the works have concentrated on finding small modules and protein complexes. The authors have extended the concept of functional module and have identified larger functional modules which are the most similar to the entire network. To this end, a new hybrid spectral-based method is proposed here. First, the original graph is transformed into a line graph. Next, the nodes of the new graph are represented in the Euclidean space by using spectral methods and finally, a self-organising map is applied to the points in the new feature space. The experimental results show that similar modules, obtained from the proposed method, have own local hubs and lots of significant functional subunits concerning each other. These modules not only detect general biological processes that each protein is involved in, but also due to great similarities to the original network, it can be used as significant subnetworks for predicting protein function as detailed as possible. Some interesting properties of these modules are also investigated in this research.

  2. Cadmium modulates adipocyte functions in metallothionein-null mice.

    Science.gov (United States)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT(-/-)) mice, which cannot form atoxic Cd-MT complexes and are used for evaluating Cd as free ions, and wild type (MT(+/+)) mice. Cd administration more significantly reduced the adipocyte size of MT(-/-) mice than that of MT(+/+) mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT(-/-) mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. © 2013. Published by Elsevier Inc. All rights reserved.

  3. Image quality enhancement method for on-orbit remote sensing cameras using invariable modulation transfer function.

    Science.gov (United States)

    Li, Jin; Liu, Zilong

    2017-07-24

    Remote sensing cameras in the visible/near infrared range are essential tools in Earth-observation, deep-space exploration, and celestial navigation. Their imaging performance, i.e. image quality here, directly determines the target-observation performance of a spacecraft, and even the successful completion of a space mission. Unfortunately, the camera itself, such as a optical system, a image sensor, and a electronic system, limits the on-orbit imaging performance. Here, we demonstrate an on-orbit high-resolution imaging method based on the invariable modulation transfer function (IMTF) of cameras. The IMTF, which is stable and invariable to the changing of ground targets, atmosphere, and environment on orbit or on the ground, depending on the camera itself, is extracted using a pixel optical focal-plane (PFP). The PFP produces multiple spatial frequency targets, which are used to calculate the IMTF at different frequencies. The resulting IMTF in combination with a constrained least-squares filter compensates for the IMTF, which represents the removal of the imaging effects limited by the camera itself. This method is experimentally confirmed. Experiments on an on-orbit panchromatic camera indicate that the proposed method increases 6.5 times of the average gradient, 3.3 times of the edge intensity, and 1.56 times of the MTF value compared to the case when IMTF is not used. This opens a door to push the limitation of a camera itself, enabling high-resolution on-orbit optical imaging.

  4. Semantic integration to identify overlapping functional modules in protein interaction networks

    Directory of Open Access Journals (Sweden)

    Ramanathan Murali

    2007-07-01

    Full Text Available Abstract Background The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. Results We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches. Conclusion The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification.

  5. Cadmium modulates adipocyte functions in metallothionein-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  6. Growing functional modules from a seed protein via integration of protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Dimitrakopoulou Konstantina

    2007-10-01

    Full Text Available Abstract Background Nowadays modern biology aims at unravelling the strands of complex biological structures such as the protein-protein interaction (PPI networks. A key concept in the organization of PPI networks is the existence of dense subnetworks (functional modules in them. In recent approaches clustering algorithms were applied at these networks and the resulting subnetworks were evaluated by estimating the coverage of well-established protein complexes they contained. However, most of these algorithms elaborate on an unweighted graph structure which in turn fails to elevate those interactions that would contribute to the construction of biologically more valid and coherent functional modules. Results In the current study, we present a method that corroborates the integration of protein interaction and microarray data via the discovery of biologically valid functional modules. Initially the gene expression information is overlaid as weights onto the PPI network and the enriched PPI graph allows us to exploit its topological aspects, while simultaneously highlights enhanced functional association in specific pairs of proteins. Then we present an algorithm that unveils the functional modules of the weighted graph by expanding a kernel protein set, which originates from a given 'seed' protein used as starting-point. Conclusion The integrated data and the concept of our approach provide reliable functional modules. We give proofs based on yeast data that our method manages to give accurate results in terms both of structural coherency, as well as functional consistency.

  7. Dynamic modelling of pectin extraction describing yield and functional characteristics

    DEFF Research Database (Denmark)

    Andersen, Nina Marianne; Cognet, T.; Santacoloma, P. A.

    2017-01-01

    A dynamic model of pectin extraction is proposed that describes pectin yield, degree of esterification and intrinsic viscosity. The dynamic model is one dimensional in the peel geometry and includes mass transport of pectin by diffusion and reaction kinetics of hydrolysis, degradation and de-este...

  8. Ethnic Differences in Insulin Sensitivity, β-Cell Function, and Hepatic Extraction Between Japanese and Caucasians

    DEFF Research Database (Denmark)

    Møller, Jonas B; Dalla Man, Chiara; Overgaard, Rune V

    2014-01-01

    : This was a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of β-cell function, hepatic extraction, and insulin sensitivity...... were assessed using C-peptide, glucose, and insulin minimal models. RESULTS: Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P ... compared with Caucasians (P insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P insulin sensitivity, β-cell function...

  9. Modulation of the pupil function of microscope objective lens for multifocal multi-photon microscopy using a spatial light modulator

    Science.gov (United States)

    Matsumoto, Naoya; Okazaki, Shigetoshi; Takamoto, Hisayoshi; Inoue, Takashi; Terakawa, Susumu

    2014-02-01

    We propose a method for high precision modulation of the pupil function of a microscope objective lens to improve the performance of multifocal multi-photon microscopy (MMM). To modulate the pupil function, we adopt a spatial light modulator (SLM) and place it at the conjugate position of the objective lens. The SLM can generate an arbitrary number of spots to excite the multiple fluorescence spots (MFS) at the desired positions and intensities by applying an appropriate computer-generated hologram (CGH). This flexibility allows us to control the MFS according to the photobleaching level of a fluorescent protein and phototoxicity of a specimen. However, when a large number of excitation spots are generated, the intensity distribution of the MFS is significantly different from the one originally designed due to misalignment of the optical setup and characteristics of the SLM. As a result, the image of a specimen obtained using laser scanning for the MFS has block noise segments because the SLM could not generate a uniform MFS. To improve the intensity distribution of the MFS, we adaptively redesigned the CGH based on the observed MFS. We experimentally demonstrate an improvement in the uniformity of a 10 × 10 MFS grid using a dye solution. The simplicity of the proposed method will allow it to be applied for calibration of MMM before observing living tissue. After the MMM calibration, we performed laser scanning with two-photon excitation to observe a real specimen without detecting block noise segments.

  10. Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.

    Science.gov (United States)

    Kahnt, Thorsten; Tobler, Philippe N

    2017-02-08

    Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.SIGNIFICANCE STATEMENT A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D2 receptors has profound effects on the functional connectivity patterns of

  11. Nanomechanics and Sodium Permeability of Endothelial Surface Layer Modulated by Hawthorn Extract WS 1442

    Science.gov (United States)

    Peters, Wladimir; Drueppel, Verena; Kusche-Vihrog, Kristina; Schubert, Carola; Oberleithner, Hans

    2012-01-01

    The endothelial glycocalyx (eGC) plays a pivotal role in the physiology of the vasculature. By binding plasma proteins, the eGC forms the endothelial surface layer (ESL) which acts as an interface between bloodstream and endothelial cell surface. The functions of the eGC include mechanosensing of blood flow induced shear stress and thus flow dependent vasodilation. There are indications that levels of plasma sodium concentrations in the upper range of normal and beyond impair flow dependent regulation of blood pressure and may therefore increase the risk for hypertension. Substances, therefore, that prevent sodium induced endothelial dysfunction may be attractive for the treatment of cardiovascular disease. By means of combined atomic force - epifluorescence microscopy we studied the impact of the hawthorn (Crataegus spp.) extract WS 1442, a herbal therapeutic with unknown mechanism of action, on the mechanics of the ESL of ex vivo murine aortae. Furthermore, we measured the impact of WS 1442 on the sodium permeability of endothelial EA.hy 926 cell monolayer. The data show that (i) the ESL contributes by about 11% to the total endothelial barrier resistance for sodium and (ii) WS 1442 strengthens the ESL resistance for sodium up to about 45%. This mechanism may explain some of the vasoprotective actions of this herbal therapeutic. PMID:22253842

  12. Nanomechanics and sodium permeability of endothelial surface layer modulated by hawthorn extract WS 1442.

    Directory of Open Access Journals (Sweden)

    Wladimir Peters

    Full Text Available The endothelial glycocalyx (eGC plays a pivotal role in the physiology of the vasculature. By binding plasma proteins, the eGC forms the endothelial surface layer (ESL which acts as an interface between bloodstream and endothelial cell surface. The functions of the eGC include mechanosensing of blood flow induced shear stress and thus flow dependent vasodilation. There are indications that levels of plasma sodium concentrations in the upper range of normal and beyond impair flow dependent regulation of blood pressure and may therefore increase the risk for hypertension. Substances, therefore, that prevent sodium induced endothelial dysfunction may be attractive for the treatment of cardiovascular disease. By means of combined atomic force-epifluorescence microscopy we studied the impact of the hawthorn (Crataegus spp. extract WS 1442, a herbal therapeutic with unknown mechanism of action, on the mechanics of the ESL of ex vivo murine aortae. Furthermore, we measured the impact of WS 1442 on the sodium permeability of endothelial EA.hy 926 cell monolayer. The data show that (i the ESL contributes by about 11% to the total endothelial barrier resistance for sodium and (ii WS 1442 strengthens the ESL resistance for sodium up to about 45%. This mechanism may explain some of the vasoprotective actions of this herbal therapeutic.

  13. Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    L. Contreras-Ruiz

    2013-01-01

    Full Text Available Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice. We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

  14. Functional EEG network analysis in schizophrenia: Evidence of larger segregation and deficit of modulation.

    Science.gov (United States)

    Gomez-Pilar, Javier; Lubeiro, Alba; Poza, Jesús; Hornero, Roberto; Ayuso, Marta; Valcárcel, César; Haidar, Karim; Blanco, José A; Molina, Vicente

    2017-06-02

    Higher mental functions depend on global cerebral functional coordination. Our aim was to study fast modulation of functional networks in schizophrenia that has not been previously assessed. Graph-theory was used to analyze the electroencephalographic (EEG) activity during an odd-ball task in 57 schizophrenia patients (18 first episode patients, FEPs) and 59 healthy controls. Clustering coefficient (CLC), characteristic path length (PL) and small-worldness (SW) were computed at baseline ([-300 0] ms prior to stimulus delivery) and response ([150 450] ms post-stimulus) windows. Clinical and cognitive assessments were performed. CLC, PL and SW showed a significant modulation between baseline and response in controls but not in patients. Patients obtained higher CLC and SW at baseline, lower CLC and higher PL at response, and diminished modulation of CLC and SW as compared to controls. In patients, CLC and SW modulation were inversely associated to cognitive performance in executive tasks and directly associated to working memory. Similar patterns were observed in FEPs. CLC and SW during the baseline were inversely associated to their respective modulation magnitudes. Our results are coherent with a hyper-segregated network at baseline (higher CLC) and a decreased modulation of the functional connectivity during cognition in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A method of extracting ontology module using concept relations for sharing knowledge in mobile cloud computing environment.

    Science.gov (United States)

    Lee, Keonsoo; Rho, Seungmin; Lee, Seok-Won

    2014-01-01

    In mobile cloud computing environment, the cooperation of distributed computing objects is one of the most important requirements for providing successful cloud services. To satisfy this requirement, all the members, who are employed in the cooperation group, need to share the knowledge for mutual understanding. Even if ontology can be the right tool for this goal, there are several issues to make a right ontology. As the cost and complexity of managing knowledge increase according to the scale of the knowledge, reducing the size of ontology is one of the critical issues. In this paper, we propose a method of extracting ontology module to increase the utility of knowledge. For the given signature, this method extracts the ontology module, which is semantically self-contained to fulfill the needs of the service, by considering the syntactic structure and semantic relation of concepts. By employing this module, instead of the original ontology, the cooperation of computing objects can be performed with less computing load and complexity. In particular, when multiple external ontologies need to be combined for more complex services, this method can be used to optimize the size of shared knowledge.

  16. A Method of Extracting Ontology Module Using Concept Relations for Sharing Knowledge in Mobile Cloud Computing Environment

    Directory of Open Access Journals (Sweden)

    Keonsoo Lee

    2014-01-01

    Full Text Available In mobile cloud computing environment, the cooperation of distributed computing objects is one of the most important requirements for providing successful cloud services. To satisfy this requirement, all the members, who are employed in the cooperation group, need to share the knowledge for mutual understanding. Even if ontology can be the right tool for this goal, there are several issues to make a right ontology. As the cost and complexity of managing knowledge increase according to the scale of the knowledge, reducing the size of ontology is one of the critical issues. In this paper, we propose a method of extracting ontology module to increase the utility of knowledge. For the given signature, this method extracts the ontology module, which is semantically self-contained to fulfill the needs of the service, by considering the syntactic structure and semantic relation of concepts. By employing this module, instead of the original ontology, the cooperation of computing objects can be performed with less computing load and complexity. In particular, when multiple external ontologies need to be combined for more complex services, this method can be used to optimize the size of shared knowledge.

  17. Rheostats and toggle switches for modulating protein function.

    Directory of Open Access Journals (Sweden)

    Sarah Meinhardt

    Full Text Available The millions of protein sequences generated by genomics are expected to transform protein engineering and personalized medicine. To achieve these goals, tools for predicting outcomes of amino acid changes must be improved. Currently, advances are hampered by insufficient experimental data about nonconserved amino acid positions. Since the property "nonconserved" is identified using a sequence alignment, we designed experiments to recapitulate that context: Mutagenesis and functional characterization was carried out in 15 LacI/GalR homologs (rows at 12 nonconserved positions (columns. Multiple substitutions were made at each position, to reveal how various amino acids of a nonconserved column were tolerated in each protein row. Results showed that amino acid preferences of nonconserved positions were highly context-dependent, had few correlations with physico-chemical similarities, and were not predictable from their occurrence in natural LacI/GalR sequences. Further, unlike the "toggle switch" behaviors of conserved positions, substitutions at nonconserved positions could be rank-ordered to show a "rheostatic", progressive effect on function that spanned several orders of magnitude. Comparisons to various sequence analyses suggested that conserved and strongly co-evolving positions act as functional toggles, whereas other important, nonconserved positions serve as rheostats for modifying protein function. Both the presence of rheostat positions and the sequence analysis strategy appear to be generalizable to other protein families and should be considered when engineering protein modifications or predicting the impact of protein polymorphisms.

  18. Canonical Wnt signaling negatively modulates regulatory T cell function

    NARCIS (Netherlands)

    Loosdregt, J. van; Fleskens, V.; Mokry, M.; Boxtel, R. van; Meerding, J.M.; Pals, C.E.G.M.; Kurek, D.; Baert, M.R.; Delemarre, E.M.; Gröne, A.; Groot Koerkamp, M.J.A.; Sijts, E.J.A.M.; Nieuwenhuis, E.E.S.; Maurice, M.M.; Es, J.H. van; Berge, D. ten; Holstege, F.C.P.; Staal, F.J.T.; Zaiss, D.M.W.; Prakken, B.J.; Coffer, P.J

    2013-01-01

    Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  19. Canonical Wnt signaling negatively modulates regulatory T cell function

    NARCIS (Netherlands)

    J. van Loosdregt (Jorg); V. Fleskens (Veerle); M.M. Tiemessen (Machteld); M. Mokry (Michal); R. van Boxtel (Ruben); J. Meerding (Jenny); C.E.G.M. Pals (Cornelieke); D. Kurek (Dorota); M.R.M. Baert (Miranda); E.M. Delemarre (Eveline); A. Gröne (Andrea); M.J.A. Groot Koerkamp (Marianne); A.J.A.M. Sijts (Alice ); E.E.S. Nieuwenhuis (Edward); M.M. Maurice (Madelon); J.H. van Es (Johan); D. ten Berge (Derk); F.C. Holstege (Frank); F.J.T. Staal (Frank); D.M.W. Zaiss (Dietmar); B.J. Prakken (Berent); P.J. Coffer (Paul)

    2013-01-01

    textabstractFoxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  20. Canonical Wnt Signaling Negatively Modulates Regulatory T Cell Function

    NARCIS (Netherlands)

    Loosdregt, J. van; Fleskens, V.; Tiemessen, M.M.; Mokry, M.; Boxtel, R. van; Meerding, J.; Pals, C.E.G.M.; Kurek, D.; Baert, M.R.; Delemarre, E.M.; Gröne, A.; Groot Koerkamp, M.J.A.; Sijts, E.J.A.M.; Nieuwenhuis, E.E.S.; Maurice, M.M.; Es, J.H. van; Berge, D. ten; Holstege, F.C.; Staal, F.J.T.; Zaiss, D.M.W.; Prakken, A.B.J.; Coffer, P.J

    2013-01-01

    Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  1. Application of the Lambert W-function for a PV module parameters' estimation

    Science.gov (United States)

    Taciuc, M.; Crǎciunescu, A.

    2017-07-01

    This paper develops a new method to determine parameters of PV modules, by using the Lambert W-function. The single-diode model was considered and the explicit form of the I-V characteristic was established. For the calculation of the numerical values of Lambert W-function, a new high speed algorithm has been proposed.

  2. A normal form for hypergraph-based module extraction for SROIQ

    CSIR Research Space (South Africa)

    Nortje, R

    2012-12-01

    Full Text Available Modularization is an important part of the modular design and maintenance of large scale ontologies. Syntactic locality modules, with their desirable model theoretic properties, play an ever increasing role in the design of algorithms...

  3. Numerical Extraction of Distributions of Space-charge and Polarization from Laser Intensity Modulation Method

    OpenAIRE

    Tuncer, Enis; Lang, Sidney B.

    2004-01-01

    The Fredholm integral equation of the laser intensity modulation method is solved with the application of the Monte Carlo technique and a least-squares solver. The numerical procedure is tested on simulated data.

  4. Sexual hormones modulate compensatory renal growth and function

    Directory of Open Access Journals (Sweden)

    Pablo J. Azurmendi

    2013-12-01

    Full Text Available The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG that follows uninephrectomy (uNx is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50% while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  5. Sexual hormones modulate compensatory renal growth and function.

    Science.gov (United States)

    Azurmendi, Pablo J; Oddo, Elisabet M; Toledo, Jorge E; Martin, Rodolfo S; Ibarra, Fernando R; Arrizurieta, Elvira E

    2013-01-01

    The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/ min/g kwt compared, with the other uNx groups, p protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  6. Screening for bioactive metabolites in plant extracts modulating glucose uptake and fat accumulation

    DEFF Research Database (Denmark)

    El-Houri, Rime Bahij; Kotowska, Dorota Ewa; C. B. Olsen, Louise

    2014-01-01

    found that dichloromethane extracts of aerial parts of golden root (Rhodiola rosea) and common elder (Sambucus nigra) as well as the dichloromethane extracts of thyme (Thymus vulgaris) and carrot (Daucus carota) were able to stimulate insulin-dependent glucose uptake in both adipocytes and myotubes...

  7. An Analysis of the Cost and Performance of Photovoltaic Systems as a Function of Module Area

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, Kelsey A.W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Fu, Ran [National Renewable Energy Lab. (NREL), Golden, CO (United States); Silverman, Tim [National Renewable Energy Lab. (NREL), Golden, CO (United States); Woodhouse, Mike [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sun, Xingshu [Purdue Univ., West Lafayette, IN (United States); Alam, Mohammed A. [Purdue Univ., West Lafayette, IN (United States)

    2017-04-07

    We investigate the potential effects of module area on the cost and performance of photovoltaic systems. Applying a bottom-up methodology, we analyzed the costs associated with mc-Si and thin-film modules and systems as a function of module area. We calculate a potential for savings of up to $0.04/W, $0.10/W, and $0.13/W in module manufacturing costs for mc-Si, CdTe, and CIGS respectively, with large area modules. We also find that an additional $0.05/W savings in balance-of-systems costs may be achieved. However, these savings are dependent on the ability to maintain efficiency and manufacturing yield as area scales. Lifetime energy yield must also be maintained to realize reductions in the levelized cost of energy. We explore the possible effects of module size on efficiency and energy production, and find that more research is required to understand these issues for each technology. Sensitivity of the $/W cost savings to module efficiency and manufacturing yield is presented. We also discuss non-cost barriers to adoption of large area modules.

  8. Alkaloid extracts from Jimson weed (Datura stramonium L.) modulate purinergic enzymes in rat brain.

    Science.gov (United States)

    Ademiluyi, Adedayo O; Ogunsuyi, Opeyemi B; Oboh, Ganiyu

    2016-09-01

    Although some findings have reported the medicinal properties of Jimson weed (Datura stramonium L.), there exist some serious neurological effects such as hallucination, loss of memory and anxiety, which has been reported in folklore. Consequently, the modulatory effect of alkaloid extracts from leaf and fruit of Jimson weed on critical enzymes of the purinergic [ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-NTDase), alkaline phosphatase (ALP) and Na + /K + ATPase] system of neurotransmission was the focus of this study. Alkaloid extracts were prepared by solvent extraction method and their interaction with the activities of these enzymes were assessed (in vitro) in rat brain tissue homogenate and in vivo in rats administered 100 and 200mg/kg body weight (p.o) of the extracts for thirty days, while administration of single dose (1mg/kg body weight; i.p.) of scopolamine served as the positive control. The extracts were also investigated for their Fe 2+ and Cu 2+ chelating abilities and GC-MS characterization of the extracts was also carried out. The results revealed that the extracts inhibited activates of E-NTPDase, E-NTDase and ALP in a concentration dependent manner, while stimulating the activity of Na + /K + ATPase (in vitro). Both extracts also exhibited Fe 2+ and Cu 2+ chelating abilities. Considering the EC 50 values, the fruit extract had significantly higher (P0.05) in both extracts' inhibitory effects on E-NTDase. The in vivo study revealed reduction in the activities of ENTPDase, E-NTDase, and Na + /K + ATPase in the extract-administered rat groups compared to the control group, while an elevation in ALP activity was observed in the extract-administered rat groups compared to the control group. GC-MS characterization revealed the presence of atropine, scopolamine, amphetamine, 3-methyoxyamphetamine, 3-ethoxyamhetamine cathine, spermine, phenlyephirine and 3-piperidinemethanol, among others in the extracts. Hence

  9. Modulation of macrophage functions by heavy metals; Modulation von Makrophagen-Funktionen durch Schwermetalle

    Energy Technology Data Exchange (ETDEWEB)

    Herder, C. [Diabetes-Forschungsinstitut an der Heinrich-Heine-Universitaet Duesseldorf (Germany)

    1999-07-01

    The investigations showed that the LPS/IFN{gamma}-induced production of mediators by bone marrow macrophages was affected more significantly by PbCl{sub 2} in NOD mice, which are prone to autoimmunodiabetes, than in C57BL/6 mice. In NOD mice, the release of TNF{alpha} was enhanced by PbCl{sub 2} while the release of NO, PGE{sub 2}, MCP-1 and IL-12(p40) was decreased. The secretion of IL-12(p70) and IL-10 remained unmodulated. The PbCl{sub 2}-induced modulation of the pattern of secernated mediators can be interpreted as a shift towards an APC1 and maybe even a Th1 phenotype. The reduction of NO production in the presence of PbCl{sub 2} is assumed to be caused by the less pronounced expression of the gene of inducible NO synthase as the volume of specific mRNA measurable by RT-PCR was reduced. The enhanced production of TNF{alpha} is assumed to be due to an effect of PbCl{sub 2} on the protein kinase C dependent signal transducetion pathways. The hypotheses of a contribution of the expression of certain mHC molecules to the reactivity with PbCl{sub 2} could not be validated. The findings illustrate the immunomodulatory properties of the environmental pollutant PbCl{sub 2} and also the particular sensitivity of NOD mice. [German] In der vorliegenden Arbeit konnte gezeigt werden, dass die LPS/IFN{gamma}-induzierte Produktion von Mediatoren durch Knochenmarksmakrophagen aus genetisch zum Autoimmundiabetes praedisponierten NOD-Maeusen deutlich staerker durch Bleichlorid (PbCl{sub 2}) beeinflusst werden kann als bei C57BL/6-Maeusen. Bei NOD-Maeusen wurde die Freisetzung von TNF4{alpha} durch PbCl{sub 2} erhoeht, die Freisetzung von NO, PGE{sub 2}, MCP-1 und IL-12(p40) erniedrigt. Nicht moduliert wurde die Sekretion von IL-12(p70) und IL-10. Die durch PbCl{sub 2} ausgeloeste Modulation des Musters sezernierter Mediatoren kann als Verschiebung in Richtung eines APC1- und in der Folge moeglicherweise auch eines Th1-Phaenotyps gedeutet werden. Die Reduktion der NO

  10. Extracts from New Zealand Undaria pinnatifida Containing Fucoxanthin as Potential Functional Biomaterials against Cancer in Vitro

    Directory of Open Access Journals (Sweden)

    Sheng Kelvin Wang

    2014-03-01

    Full Text Available This study tested extracts from New Zealand seaweed Undaria pinnatifida containing fucoxanthin, in parallel with pure fucoxanthin, in nine human cancer cell lines, for anticancer activity. Growth inhibition effects of extracts from Undaria pinnatifida were found in all types of cancer cell lines in dose- and time- dependent manners. Cytotoxicity of fucoxanthin in three human non-cancer cell lines was also tested. Compared with pure fucoxanthin, our extracts containing low level of fucoxanthin were found to be more effective in inhibiting the growth of lung carcinoma, colon adenocarcinoma and neuroblastoma. Our results suggest that fucoxanthin is a functional biomaterial that may be used as a chemopreventive phytochemical or in combination chemotherapy. Furthermore, we show for the first time that some unknown compounds with potential selective anti-cancer effects may exist in extracts of New Zealand Undaria pinnatifida, and New Zealand Undaria pinnatifida could be used as a source for either functional biomaterial extraction or production of functional food.

  11. [The analysis of the sampling modulation transfer function and the influence on the Gaussian spectra].

    Science.gov (United States)

    Zhao, Lie-Feng; Xu, Zhi-Hai; Feng, Hua-Jun; Li, Qi

    2009-06-01

    As the parameters of the photoelectric detector have important effects on the performance of the dispersive spectrometers, it is necessary to detail the discrete sampling process of the photoelectric detector array. In the present paper, the sampling model was setup, and the effects on the sampling results caused by the spatial frequency of the cosine signal, the width of the sampling pixel, and the initial phase of the sampling pixel position to the crest of the input cosine signal were discussed thoroughly in the frequency domain. By introducing the integral function, a general expression of the sampling modulation transfer function was given, and the concept and expression of the average sampling modulation transfer function was proposed. Since that expression eliminates the effect of initial phase, it is much more convenient to the practical applications. For the typical Gaussian spectrum produced by the dispersive spectrometer, the Fourier transform result of that spectrum was multiplied by the average sampling modulation transfer function to produce a functional expression of the modulation transfer function of the whole system. The average aliasing error of the sampling process was expressed as a function of spatial frequencies; the relationship between the peak value of the average aliasing error and the width of the Gaussian spectrum was discussed; and the critical value of the spectrum width to restore this spectrum precisely was proposed. That critical value is significant for providing guidance to the design and fabrication of dispersive spectrometers.

  12. Enhanced Microbial, Functional and Sensory Properties of Herbal Yogurt Fermented with Korean Traditional Plant Extracts

    Science.gov (United States)

    Joung, Jae Yeon; Lee, Ji Young; Ha, Young Sik; Shin, Yong Kook; Kim, Younghoon; Kim, Sae Hun; Oh, Nam Su

    2016-01-01

    This study evaluated the effects of two Korean traditional plant extracts (Diospyros kaki THUNB. leaf; DK, and Nelumbo nucifera leaf; NN) on the fermentation, functional and sensory properties of herbal yogurts. Compared to control fermentation, all plant extracts increased acidification rate and reduced the time to complete fermentation (pH 4.5). Supplementation of plant extracts and storage time were found to influence the characteristics of the yogurts, contributing to increased viability of starter culture and phenolic compounds. In particular, the increase in the counts of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus was highest (2.95 and 1.14 Log CFU/mL respectively) in DK yogurt. Furthermore, supplementation of the plant extracts significantly influenced to increase the antioxidant activity and water holding capacity and to produce volatile compounds. The higher antioxidant activity and water holding capacity were observed in NN yogurt than DK yogurt. Moreover, all of the sensory characteristics were altered by the addition of plant extracts. Addition of plant extracts increased the scores related to flavor, taste, and texture from plain yogurt without a plant extract, as a result of volatile compounds analysis. Thus, the overall preference was increased by plant extracts. Consequently, supplementation of DK and NN extracts in yogurt enhanced the antioxidant activity and physical property, moreover increased the acceptability of yogurt. These findings demonstrate the possibility of using plant extracts as a functional ingredient in the manufacture of herbal yogurt. PMID:27499669

  13. Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function.

    Science.gov (United States)

    Hollands, Wendy J; Saha, Shikha; Hayran, Osman; Boyko, Nadiya; Glibetic, Maria; Konic-Ristic, Aleksandra; Jorjadze, Mariam; Kroon, Paul A

    2013-11-01

    The health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. These data do not support the notion that these plant bioactives can improve human platelet function. © 2013 Society of Chemical Industry.

  14. Altered Functional Connectivity within and between Brain Modules in Absence Epilepsy: A Resting-State Functional Magnetic Resonance Imaging Study

    Directory of Open Access Journals (Sweden)

    Cui-Ping Xu

    2013-01-01

    Full Text Available Functional connectivity has been correlated with a patient’s level of consciousness and has been found to be altered in several neuropsychiatric disorders. Absence epilepsy patients, who experience a loss of consciousness, are assumed to suffer from alterations in thalamocortical networks; however, previous studies have not explored the changes at a functional module level. We used resting-state functional magnetic resonance imaging to examine the alteration in functional connectivity that occurs in absence epilepsy patients. By parcellating the brain into 90 brain regions/nodes, we uncovered an altered functional connectivity within and between functional modules. Some brain regions had a greater number of altered connections and therefore behaved as key nodes in the changed network pattern; these regions included the superior frontal gyrus, the amygdala, and the putamen. In particular, the superior frontal gyrus demonstrated both an increased value of connections with other nodes of the frontal default mode network and a decreased value of connections with the limbic system. This divergence is positively correlated with epilepsy duration. These findings provide a new perspective and shed light on how functional connectivity and the balance of within/between module connections may contribute to both the state of consciousness and the development of absence epilepsy.

  15. Predictability of Genetic Interactions from Functional Gene Modules

    Directory of Open Access Journals (Sweden)

    Jonathan H. Young

    2017-02-01

    Full Text Available Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.

  16. A Rhodiola rosea root extract protects skeletal muscle cells against chemically induced oxidative stress by modulating heat shock protein 70 (HSP70) expression.

    Science.gov (United States)

    Hernández-Santana, Aaron; Pérez-López, Verónica; Zubeldia, Jose María; Jiménez-del-Rio, Miguel

    2014-04-01

    Rhodiola rosea is a perennial plant in the Crassulaceae family, recently postulated to exert its adaptogenic functions partially by modulating the expression of molecular factors such as heat shock proteins (HSP). The aim of this study was to analyze the efficacy of a Rhodiola rosea extract (Rhodiolife) in protecting murine skeletal muscle cells (C2 C12 myotubes) from chemically induced oxidative stress and to establish whether modulation of HSP70 expression is observed. C2 C12 cells treated with Rhodiolife did not experience any loss of viability (p > 0.05) at concentrations of 1-100 µg/mL for up to 24 h. In control cultures, viability decreased 25% following exposure to 2 mM H2 O2 (1 h). However, no significant decrease in viability in cells pre-treated with extract at concentrations as low as 1 µg/mL was observed. HSP70 mRNA levels were up-regulated two-fold in cell cultures treated with Rhodiolife (10 µg/mL), and expression was further enhanced by exposure to H2 O2 (six-fold, p < 0.05). HSP70 protein levels were maintained in pre-treated cell cultures compared to controls but was significantly lower (-50%) in cells lacking treatment exposed to H2 O2 . The present results indicate that Rhodiolife protects C2 C12 myotubes against peroxide-induced oxidative stress through the modulation of the molecular chaperone HSP70. Copyright © 2013 John Wiley & Sons, Ltd.

  17. A Romanian Prosody Prediction Module Based on a Functional Intonational Model

    Directory of Open Access Journals (Sweden)

    Doina Jitca

    2012-10-01

    Full Text Available This paper presents a prosodic prediction module used by the Romanian Text-to-Speech (TtS system in intonation synthesis. The prosody prediction refers to the surface generation of the F0 contour, based on the F0 patterns assigned to the functional categories of the prosodic units. Prior to the prediction module presentation, the paper includes a summary of these functional categories and the partial melodic contour descriptions based on functional labels. The block diagram of the prediction module outlines two main processing steps: the phrasing prediction for building the utterance tree and the selection of the melodic contours of its groups. Both processing steps are exemplified within a case study of Romanian text speech synthesis. The prosody prediction results are discussed and compared with natural F0 contours of different speakers.

  18. Study on cytokine modulation in mast cell-induced allergic reactions by using gamma-irradiated natural herbal extracts

    Energy Technology Data Exchange (ETDEWEB)

    Gwon, Hui Jeong; Lim, Youn Mook; Kim, Yong Soo; Nho, Young Chang [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Kim Hae Kyoung [Chonbuk National University, Jeonju (Korea, Republic of)

    2009-12-15

    We previously described that some natural herbal extracts such as Houttuynia cordata (H), Centella asiatica (C), Plantago asiatica (P), Morus alba L. (M), and Ulmus davidiana (U), differentially suppress an atopic dermatitis like skin lesions. The objective of this study was to evaluate the pro-inflammatory cytokine modulation of the water extract of the H, C, P, M, U, and those mixtures (M) and their mechanism in a phorbol myristate acetate (PMA) plus calcium inopore A23187 treated human mast cell line (HMC-1). The H, C, P, M, U, and M inhibited the inflammatory cytokines such as TNF-{alpha}, IL-6 and IL-8 stimulated by PMA plus A23187 from HMC-1 cells. In addition, the M did not significantly affect the cell viability and had no toxicity on the HMC-1 cells. Based on these results, M can be used for the treatment of an allergic inflammation response.

  19. Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions

    OpenAIRE

    Browning, Kirsteen N.; Travagli, R. Alberto

    2014-01-01

    Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathet...

  20. Fish oil supplementation modulates immune function in healthy infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja M.R.

    2007-01-01

    (n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 3 2 intervention in 64 healthy......-a, INF-g, and IL-10 concentrations in whole-blood cultures, stimulated for 22 h with LPS1phytohemaglutinin (PHA) or Lactobacillus paracasei, were also determined. IgA was measured in feces when infants were 10 mo of age. FO supplementation effectively raised erythrocyte (n-3) PUFA (P , 0.001), increased......, this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation. The implications for later health need further investigation. J...

  1. Fish oil supplementation modulates immune function in healthy infants

    DEFF Research Database (Denmark)

    Damsgaard, C.T.; Lauritzen, L.; Kjaer, T.M.R.

    2007-01-01

    (n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 x 2 intervention in 64 healthy......-alpha, INF-gamma, and IL-10 concentrations in whole-blood cultures, stimulated for 22 h with LPS+phytohema-glutinin (PHA) or Lactobacillus paracasei, were also determined. IgA was measured in feces when infants were 10 mo of age. FO supplementation effectively raised erythrocyte (n-3) PUFA (P ..., this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation. The implications for later health need further investigation....

  2. Hijacking mitochondria: bacterial toxins that modulate mitochondrial function.

    Science.gov (United States)

    Jiang, Jhih-Hang; Tong, Janette; Gabriel, Kipros

    2012-05-01

    Bacterial infection has enormous global social and economic impacts stemming from effects on human health and agriculture. Although there are still many unanswered questions, decades of research has uncovered many of the pathogenic mechanisms at play. It is now clear that bacterial pathogens produce a plethora of proteins known as "toxins" and "effectors" that target a variety of physiological host processes during the course of infection. One of the targets of host targeted bacterial toxins and effectors are the mitochondria. The mitochondrial organelles are major players in many biological functions, including energy conversion to ATP and cell death pathways, which inherently makes them targets for bacterial proteins. We present a summary of the toxins targeted to mitochondria and for those that have been studied in finer detail, we also summarize what we know about the mechanisms of targeting and finally their action at the organelle. Copyright © 2012 Wiley Periodicals, Inc.

  3. Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response...... was evaluated. Ovomucoid fed alone resulted in oral tolerance induction measured as both a reduced ovomucoid-pecific spleen cell proliferation and antibody response. Feeding kidney-bean extract prevented induction of oral tolerance to ovomucoid measured as spleen cell proliferation in vitro. Pure kidney......-bean lectin also prevented oral tolerance induction, suggesting that lectin in the kidney-bean extract caused inhibition of oral tolerance. Parenteral administration (intravenous and intraperitoneal) of pure kidney-bean lectin had no significant influence on oral tolerance induction. Soyabean extract also...

  4. Extract of Reishi Polysaccharides Induces Cytokine Expression via TLR4-Modulated Protein Kinase Signaling Pathways

    National Research Council Canada - National Science Library

    Hsu, Hsien-Yeh; Hua, Kuo-Feng; Lin, Chun-Cheng; Lin, Chun-Hung; Hsu, Jason; Wong, Chi-Huey

    2004-01-01

    ...; ¶ Stuyvesant School, New York, NY 10282; and || Scripps Research Institute, La Jolla, CA 92037 We have demonstrated that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP...

  5. Modulation by Polypodium leucotomos extract of cytokine patterns in experimental trichomoniasis model

    National Research Council Canada - National Science Library

    Nogal-Ruiz J.J; Gómez-Barrio A; Escario J.A; Martínez-Fernández A.R

    2003-01-01

    The immunomodulating effects of Anapsos®, an aqueous hydrosoluble extract obtained from the rhizomes of the fern Polypodium leucotomos, on both pathogenicity and cytokine levels in serum (IFN-γ/IL-4...

  6. Modulating effects of oatmeal extracts in the sodium lauryl sulfate skin irritancy model.

    Science.gov (United States)

    Vié, K; Cours-Darne, S; Vienne, M P; Boyer, F; Fabre, B; Dupuy, P

    2002-01-01

    The aim of the present study was to assess the anti-inflammatory activity of two topically applied oatmeal extracts, i.e. Avena sativa and Avena Rhealba, using the sodium lauryl sulfate (SLS) irritation model. At baseline, test areas on the volar surface of the upper arms of 12 healthy individuals were pretreated with the two extracts and their vehicle (petrolatum ointment) under occlusion for 2 h, and one site was left untreated. Then a patch with a 1% SLS solution was applied to the test sites for 24 h. Irritation was determined at each period by measuring by chromametry and laser-Doppler. In a dose-ranging study with the Avena Rhealba extract alone, the 20 and 30% concentrations exerted a slight inhibition of the a* parameter increase and a marked reduction of the blood flow increase (p oatmeal extracts on skin irritation in the SLS model. Copyright 2002 S. Karger AG, Basel

  7. Oct4 targets regulatory nodes to modulate stem cell function.

    Directory of Open Access Journals (Sweden)

    Pearl A Campbell

    2007-06-01

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  8. Identification of functional modules by integration of multiple data sources using a Bayesian network classifier.

    Science.gov (United States)

    Wang, Jinlian; Zuo, Yiming; Liu, Lun; Man, Yangao; Tadesse, Mahlet G; Ressom, Habtom W

    2014-04-01

    Prediction of functional modules is indispensable for detecting protein deregulation in human complex diseases such as cancer. Bayesian network is one of the most commonly used models to integrate heterogeneous data from multiple sources such as protein domain, interactome, functional annotation, genome-wide gene expression, and the literature. In this article, we present a Bayesian network classifier that is customized to (1) increase the ability to integrate diverse information from different sources, (2) effectively predict protein-protein interactions, (3) infer aberrant networks with scale-free and small-world properties, and (4) group molecules into functional modules or pathways based on the primary function and biological features. Application of this model in discovering protein biomarkers of hepatocellular carcinoma leads to the identification of functional modules that provide insights into the mechanism of the development and progression of hepatocellular carcinoma. These functional modules include cell cycle deregulation, increased angiogenesis (eg, vascular endothelial growth factor, blood vessel morphogenesis), oxidative metabolic alterations, and aberrant activation of signaling pathways involved in cellular proliferation, survival, and differentiation. The discoveries and conclusions derived from our customized Bayesian network classifier are consistent with previously published results. The proposed approach for determining Bayesian network structure facilitates the integration of heterogeneous data from multiple sources to elucidate the mechanisms of complex diseases.

  9. Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function.

    Science.gov (United States)

    Joven, Jorge; March, Isabel; Espinel, Eugenia; Fernández-Arroyo, Salvador; Rodríguez-Gallego, Esther; Aragonès, Gerard; Beltrán-Debón, Raúl; Alonso-Villaverde, Carlos; Rios, Lidia; Martin-Paredero, Vicente; Menendez, Javier A; Micol, Vicente; Segura-Carretero, Antonio; Camps, Jordi

    2014-06-01

    Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effect of Commiphora mukul extract on cardiac dysfunction and ventricular function in isoproterenol-induced myocardial infarction.

    Science.gov (United States)

    Ojha, Shreesh K; Nandave, Mukesh; Arora, Sachin; Mehra, Raj D; Joshi, Sujata; Narang, Rajiv; Arya, D S

    2008-09-01

    In present study, hydroalcoholic extract of C. mukul significantly improved the cardiac function and prevented myocardial ischemic impairment manifested in the form of increased heart rate, decreased arterial pressure, increased left ventricular end diastolic pressure, and altered myocardial contractility indices. C. mukul treatment additionally also produced a significant increase in lactate dehydrogenase levels and prevented decline of protein content in heart. C. mukul preserved the structural integrity of myocardium. Reduced leakage of myocyte enzyme lactate dehydrogenase and maintenance of structural integrity of myocardium along with favorable modulation of cardiac function and improved cardiac performance indicate the salvage of myocardium with C. mukul treatment. Guggulsterones which are considered to be responsible for most of the therapeutic properties of C. mukul may underlie the observed cardioprotective effect of C. mukul against cardiac dysfunction in isoproterenol-induced ischemic rats.

  11. Medicinal plant extracts modulate respiratory burst and proliferation activity of rainbow trout (Oncorhynchus mykiss) leukocytes.

    Science.gov (United States)

    Bulfon, Chiara; Galeotti, Marco; Volpatti, Donatella

    2017-09-01

    The present study was designed to investigate the immunomodulatory effects of Aloe vera, Curcuma longa, Echinacea purpurea, Lavandula officinalis, Origanum vulgare, Panax ginseng, and Rheum officinale extracts on leukocytes purified from rainbow trout (Oncorhynchus mykiss) head kidney. The cells were cultured in a medium containing increasing doses of extracts; afterwards, they were tested for reactive oxygen species production after stimulation with phorbol myristate acetate (PMA) and proliferation in the presence or absence of phytohemagglutinin from Phaseolus vulgaris (PHA-P). After a 2-h exposure, the extracts of L. officinalis, O. vulgare, and R. officinale strongly reduced the oxidative burst activity of PMA-stimulated leukocytes, in a dose-dependent manner (P ≤ 0.05). A. vera, C. longa, E. purpurea, and P. ginseng extracts reduced this response with lower efficacy and especially at lower concentrations. On the contrary, the highest concentration of ginseng extract stimulated the respiratory burst of leukocytes compared to untreated control cells. After a 72-h exposure, the extracts of L. officinalis, R. officinale, C. longa, E. purpurea, and P. ginseng had a clear dose-dependent stimulatory effect on leukocyte proliferation (P ≤ 0.05). The results suggest that these medicinal plants can be considered as reliable sources of new antioxidants or immunostimulants to be used in aquaculture.

  12. Screening for Bioactive Metabolites in Plant Extracts Modulating Glucose Uptake and Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Rime B. El-Houri

    2014-01-01

    Full Text Available Dichloromethane and methanol extracts of seven different food and medicinal plants were tested in a screening platform for identification of extracts with potential bioactivity related to insulin-dependent glucose uptake and fat accumulation. The screening platform included a series of in vitro bioassays, peroxisome proliferator-activated receptor (PPAR γ-mediated transactivation, adipocyte differentiation of 3T3-L1 cell cultures, and glucose uptake in both 3T3-L1 adipocytes and primary porcine myotubes, as well as one in vivo bioassay, fat accumulation in the nematode Caenorhabditis elegans. We found that dichloromethane extracts of aerial parts of golden root (Rhodiola rosea and common elder (Sambucus nigra as well as the dichloromethane extracts of thyme (Thymus vulgaris and carrot (Daucus carota were able to stimulate insulin-dependent glucose uptake in both adipocytes and myotubes while weekly activating PPARγ without promoting adipocyte differentiation. In addition, these extracts were able to decrease fat accumulation in C. elegans. Methanol extracts of summer savory (Satureja hortensis, common elder, and broccoli (Brassica oleracea enhanced glucose uptake in myotubes but were not able to activate PPARγ, indicating a PPARγ-independent effect on glucose uptake.

  13. Modulating role of Semecarpus anacardium L. nut milk extract on aflatoxin B(1) biotransformation.

    Science.gov (United States)

    Premalatha, B; Sachdanandam, P

    2000-01-01

    As part of a substantial effort to curtail the adverse health effects posed by aflatoxin B(1), studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of Semecarpus anacardium nut extract against aflatoxin B(1)-induced hepatocellular carcinoma. Rats are monitored for levels of urinary, serum and liver biomarkers, namely, unmetabolised aflatoxin B(1), and its metabolites aflatoxin M(1), and aflatoxin Q(1), over the course of 2 weeks with nut extract therapy following a single-exposure to aflatoxin B(1). Due to the administration of nut extract, the excretion of unmetabolised aflatoxin B(1) was increased in day 1 urine when compared with rats without drug treatment. In serum and liver which were collected on day 16 and the rest of periodical urine samples showed aflatoxin B(1) and its metabolites in undetectable levels. The nut extract administration induced cytochrome P(450), glutathione, and glutathione-S-transferase levels in liver homogenates of aflatoxin B(1)-treated rats. These data seem to indicate that anticarcinogenic action by Semecarpus anacardium nut extract is possibly via suppression of aflatoxin B(1)activation and through interaction with microsomal-activating components. Previous evidence from this laboratory about the potency of Semecarpus anacardium nut extract against aflatoxin B(1)-induced hepatocellular carcinoma together with the present results suggest that extremely effective therapeutic protection can be achieved by this drug against aflatoxin B(1)-mediated ill effects. Copyright 2000 Academic Press.

  14. The expression of cyclic adenosine monophosphate responsive element modulator in rat sertoli cells following seminal extract administration

    Science.gov (United States)

    Akmal, Muslim; Siregar, Tongku Nizwan; Wahyuni, Sri; Hamny; Nasution, Mustafa Kamal; Indriati, Wiwik; Panjaitan, Budianto; Aliza, Dwinna

    2016-01-01

    Aim: This study aims to determine the effect of seminal vesicle extract on cyclic adenosine monophosphate responsive element modulator (CREM) expression in rat Sertoli cells. Materials and Methods: This study examined the expression of CREM on 20 male rats (Rattus norvegicus) at 4 months of age, weighing 250-300 g. The rats were divided into four groups: K0, KP1, KP2, and KP3. K0 group was injected with 0.2 ml normal saline; KP1 was injected with 25 mg cloprostenol (Prostavet C, Virbac S. A); KP2 and KP3 were injected with 0.2 and 0.4 ml seminal vesicle extract, respectively. The treatments were conducted 5 times within 12-day interval. At the end of the study, the rats were euthanized by cervical dislocation; then, the testicles were necropsied and processed for histology observation using immunohistochemistry staining. Results: CREM expression in rat Sertoli cells was not altered by the administration of either 0.2 or 0.4 ml seminal vesicle extract. Conclusion: The administration of seminal vesicle extract is unable to increase CREM expression in rat Sertoli cells. PMID:27733803

  15. Signal Quality Enhancement of Directly- Modulated VCSELs Using a Micro-Ring Resonator Transfer Function

    DEFF Research Database (Denmark)

    An, Yi; Muller, M.; Estaran Tolosa, Jose Manuel

    2013-01-01

    A micro-ring resonator transfer function is used to enhance the quality of signals generated using directly modulated VCSELs. The scheme is demonstrated up to 25 Gbit/s with a 17.6-GHz VCSEL, with up to 10 dB sensitivity improvement.......A micro-ring resonator transfer function is used to enhance the quality of signals generated using directly modulated VCSELs. The scheme is demonstrated up to 25 Gbit/s with a 17.6-GHz VCSEL, with up to 10 dB sensitivity improvement....

  16. Event related desynchronization-modulated functional electrical stimulation system for stroke rehabilitation: A feasibility study

    Directory of Open Access Journals (Sweden)

    Takahashi Mitsuru

    2012-08-01

    Full Text Available Abstract Background We developed an electroencephalogram-based brain computer interface system to modulate functional electrical stimulation (FES to the affected tibialis anterior muscle in a stroke patient. The intensity of FES current increased in a stepwise manner when the event-related desynchronization (ERD reflecting motor intent was continuously detected from the primary cortical motor area. Methods We tested the feasibility of the ERD-modulated FES system in comparison with FES without ERD modulation. The stroke patient who presented with severe hemiparesis attempted to perform dorsiflexion of the paralyzed ankle during which FES was applied either with or without ERD modulation. Results After 20 minutes of training, the range of movement at the ankle joint and the electromyography amplitude of the affected tibialis anterior muscle were significantly increased following the ERD-modulated FES compared with the FES alone. Conclusions The proposed rehabilitation technique using ERD-modulated FES for stroke patients was feasible. The system holds potentials to improve the limb function and to benefit stroke patients.

  17. Wavelet and K-L Seperability Based Feature Extraction Method for Functional Data Classification

    OpenAIRE

    Jun Wan; Zehua Chen; Yingwu Chen; Zhidong Bai

    2010-01-01

    This paper proposes a novel feature extraction method, based on Discrete Wavelet Transform (DWT) and K-L Seperability (KLS), for the classification of Functional Data (FD). This method combines the decorrelation and reduction property of DWT and the additive independence property of KLS, which is helpful to extraction classification features of FD. It is an advanced approach of the popular wavelet based shrinkage method for functional data reduction and classification. A ...

  18. Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

    Directory of Open Access Journals (Sweden)

    R.A. Johnson

    1999-01-01

    Full Text Available Carbon monoxide (CO is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1 heme-derived CO generated within vascular smooth muscle (VSM can promote vasodilation, but 2 its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.

  19. Acupuncture modulates resting state hippocampal functional connectivity in Alzheimer disease.

    Science.gov (United States)

    Wang, Zhiqun; Liang, Peipeng; Zhao, Zhilian; Han, Ying; Song, Haiqing; Xu, Jianyang; Lu, Jie; Li, Kuncheng

    2014-01-01

    Our objective is to clarify the effects of acupuncture on hippocampal connectivity in patients with Alzheimer disease (AD) using functional magnetic resonance imaging (fMRI). Twenty-eight right-handed subjects (14 AD patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all subjects. MRI was performed using a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired baseline resting state data during the initial 3 minutes and then performed acupuncture stimulation on the Tai chong and He gu acupoints for 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using statistical parametric mapping (SPM5) software. Two-sample t-tests were performed using data from the two groups in different states. We found that during the resting state, several frontal and temporal regions showed decreased hippocampal connectivity in AD patients relative to control subjects. During the resting state following acupuncture, AD patients showed increased connectivity in most of these hippocampus related regions compared to the first resting state. In conclusion, we investigated the effect of acupuncture on AD patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong and He gu can enhance the hippocampal connectivity in AD patients.

  20. Combined fish oil and astaxanthin supplementation modulates rat lymphocyte function.

    Science.gov (United States)

    Otton, Rosemari; Marin, Douglas Popp; Bolin, Anaysa Paola; de Cássia Santos Macedo, Rita; Campoio, Thais Regina; Fineto, Claudio; Guerra, Beatriz Alves; Leite, José Roberto; Barros, Marcelo Paes; Mattei, Rita

    2012-09-01

    Higher intakes of n-3 polyunsaturated fatty acids that are abundant in marine fishes have been long described as a "good nutritional intervention" with increasing clinical benefits to cardiovascular health, inflammation, mental, and neurodegenerative diseases. The present study was designed to investigate the effect of daily fish oil (FO-10 mg EPA/kg body weight (BW) and 7 mg DHA/kg BW) intake by oral gavage associated with the antioxidant astaxanthin (ASTA-1 mg/kg BW) on the redox metabolism and the functional properties of lymphocytes from rat lymph nodes. This study was conducted by measurements of lymphocyte proliferation capacity, ROS production [superoxide (O₂(•-)) and hydrogen peroxide (H₂O₂)], nitric oxide (NO(•)) generation, intracellular calcium release, oxidative damage to lipids and proteins, activities of major antioxidant enzymes, GSH/GSSG content, and cytokines release. After 45 days of FO + ASTA supplementation, the proliferation capacity of activated T- and B-lymphocytes was significantly diminished followed by lower levels of O₂(•-), H₂O₂ and NO(•) production, and increased activities of total/SOD, GR and GPx, and calcium release in cytosol. ASTA was able to prevent oxidative modification in cell structures through the suppression of the oxidative stress condition imposed by FO. L: -selectin was increased by FO, and IL-1β was decreased only by ASTA supplementation. We can propose that association of ASTA with FO could be a good strategy to prevent oxidative stress induced by polyunsaturated fatty acids and also to potentiate immuno-modulatory effects of FO.

  1. Impact of shear rate modulation on vascular function in humans.

    Science.gov (United States)

    Tinken, Toni M; Thijssen, Dick H J; Hopkins, Nicola; Black, Mark A; Dawson, Ellen A; Minson, Christopher T; Newcomer, Sean C; Laughlin, M Harold; Cable, N Timothy; Green, Daniel J

    2009-08-01

    Shear stress is an important stimulus to arterial adaptation in response to exercise and training in humans. We recently observed significant reverse arterial flow and shear during exercise and different antegrade/retrograde patterns of shear and flow in response to different types of exercise. The purpose of this study was to simultaneously examine flow-mediated dilation, a largely NO-mediated vasodilator response, in both brachial arteries of healthy young men before and after 30-minute interventions consisting of bilateral forearm heating, recumbent leg cycling, and bilateral handgrip exercise. During each intervention, a cuff inflated to 60 mm Hg was placed on 1 arm to unilaterally manipulate the shear rate stimulus. In the noncuffed arm, antegrade flow and shear increased similarly in response to each intervention (ANOVA; P<0.001, no interaction between interventions; P=0.71). Baseline flow-mediated dilation (4.6%, 6.9%, and 6.7%) increased similarly in response to heating, handgrip, and cycling (8.1%, 10.4%, and 8.9%, ANOVA; P<0.001, no interaction; P=0.89). In contrast, cuffed arm antegrade shear rate was lower than in the noncuffed arm for all of the conditions (P<0.05), and the increase in flow-mediated dilation was abolished in this arm (4.7%, 6.7%, and 6.1%; 2-way ANOVA: all conditions interacted P<0.05). These results suggest that differences in the magnitude of antegrade shear rate transduce differences in endothelial vasodilator function in humans, a finding that may have relevance for the impact of different exercise interventions on vascular adaptation in humans.

  2. Disagreement between capture probabilities extracted from capture and quasi-elastic backscattering excitation functions

    Energy Technology Data Exchange (ETDEWEB)

    Sargsyan, V.V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Yerevan State University, Yerevan (Armenia); Adamian, G.G.; Antonenko, N.V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Gomes, R.P.S. [Universidade Federal Fluminense, Instituto de Fisica, Niteroi, R.J. (Brazil)

    2014-12-01

    Experimental quasi-elastic backscattering and capture (fusion) excitation functions are usually used to extract the s -wave capture probabilities for the heavy-ion reactions. We investigated the {sup 16}O + {sup 120}Sn, {sup 144}Sm, {sup 208}Pb systems at energies near and below the corresponding interaction barriers and concluded that the probabilities extracted from quasi-elastic data are much larger than the ones extracted from fusion excitation functions at sub and deep-sub barrier energies. This seems to be a reasonable explanation for the known disagreement observed in the literature for the nuclear potential diffuseness derived from both methods. (orig.)

  3. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oyang Yen-Jen

    2010-10-01

    Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

  4. MonaLisa--visualization and analysis of functional modules in biochemical networks.

    Science.gov (United States)

    Einloft, Jens; Ackermann, Jörg; Nöthen, Joachim; Koch, Ina

    2013-06-01

    Structural modeling of biochemical networks enables qualitative as well as quantitative analysis of those networks. Automated network decomposition into functional modules is a crucial point in network analysis. Although there exist approaches for the analysis of networks, there is no open source tool available that combines editing, visualization and the computation of steady-state functional modules. We introduce a new tool called MonaLisa, which combines computation and visualization of functional modules as well as an editor for biochemical Petri nets. The analysis techniques allow for network decomposition into functional modules, for example t-invariants (elementary modes), maximal common transition sets, minimal cut sets and t-clusters. The graphical user interface provides various functionalities to construct and modify networks as well as to visualize the results of the analysis. MonaLisa is licensed under the Artistic License 2.0. It is freely available at http://www.bioinformatik.uni-frankfurt.de/software.html. MonaLisa requires at least Java 6 and runs under Linux, Microsoft Windows and Mac OS.

  5. Ulipristal acetate resembles mifepristone in modulating human fallopian tube function.

    Science.gov (United States)

    Li, Hang Wun Raymond; Liao, Su-Bin; Yeung, William Shu-Biu; Ng, Ernest Hung-Yu; O, Wai-Sum; Ho, Pak-Chung

    2014-10-10

    Do ulipristal acetate (UPA) and mifepristone have an effect on ciliary beat frequency and muscular contractions in the human Fallopian tube? UPA, in resemblance to mifepristone, inhibits ciliary beat and muscular contraction of the human Fallopian tube, probably through an agonistic effect on the tubal progesterone receptor. UPA, like mifepristone, acts as an emergency contraceptive mainly by inhibiting ovulation. Little is known about its effects on tubal function. This was an in vitro experimental study using Fallopian tube samples collected from 11 women undergoing hysterectomy for benign non-tubal gynaecological conditions. The tubal epithelium and longitudinal smooth muscle fibres were isolated, cultured and treated with UPA at graded concentrations of 0, 20, 200 and 2000 ng/ml, and mifepristone at graded concentrations of 0, 300, 3000 and 30 000 ng/ml, respectively. After treatment, ciliary beat frequency was determined using a photometric method. Basal tone, amplitude and frequency of muscular contraction were recorded through a force transducer. The mRNA expression of progesterone receptor (total and PR-B isoform), glycodelin and adrenomedullin were determined by real-time quantitative PCR. There was an overall dose-dependent suppressive effect on ciliary beat frequency (P < 0.0001) after treatment with UPA at all concentrations and with mifepristone at 3000 ng/ml or above. The basal tone, amplitude and frequency of muscular contractions were significantly reduced (P < 0.05) after treatment with UPA at 200 ng/ml or above, and with mifepristone at 3000 ng/ml or above. UPA treatment at 200 ng/ml or above significantly up-regulated the mRNA expression of progesterone receptor and glycodelin and down-regulated the mRNA expression of adrenomedullin in Fallopian tube tissue (P < 0.05). Whether or not the tubal effect may translate into additional mechanisms for contraceptive action in vivo is uncertain. The clinical relevance of UPA with regard to contraceptive

  6. Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and Extend Lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Won, Seong-Min; Cha, Hye-Uk; Yi, Sun Shin; Kim, Sung-Jo; Park, Sang-Kyu

    2016-09-08

    Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.

  7. Plasmid Replicons from Pseudomonas Are Natural Chimeras of Functional, Exchangeable Modules

    Science.gov (United States)

    Bardaji, Leire; Añorga, Maite; Ruiz-Masó, José A.; del Solar, Gloria; Murillo, Jesús

    2017-01-01

    Plasmids are a main factor for the evolution of bacteria through horizontal gene exchange, including the dissemination of pathogenicity genes, resistance to antibiotics and degradation of pollutants. Their capacity to duplicate is dependent on their replication determinants (replicon), which also define their bacterial host range and the inability to coexist with related replicons. We characterize a second replicon from the virulence plasmid pPsv48C, from Pseudomonas syringae pv. savastanoi, which appears to be a natural chimera between the gene encoding a newly described replication protein and a putative replication control region present in the widespread family of PFP virulence plasmids. We present extensive evidence of this type of chimerism in structurally similar replicons from species of Pseudomonas, including environmental bacteria as well as plant, animal and human pathogens. We establish that these replicons consist of two functional modules corresponding to putative control (REx-C module) and replication (REx-R module) regions. These modules are functionally separable, do not show specificity for each other, and are dynamically exchanged among replicons of four distinct plasmid families. Only the REx-C module displays strong incompatibility, which is overcome by a few nucleotide changes clustered in a stem-and-loop structure of a putative antisense RNA. Additionally, a REx-C module from pPsv48C conferred replication ability to a non-replicative chromosomal DNA region containing features associated to replicons. Thus, the organization of plasmid replicons as independent and exchangeable functional modules is likely facilitating rapid replicon evolution, fostering their diversification and survival, besides allowing the potential co-option of appropriate genes into novel replicons and the artificial construction of new replicon specificities. PMID:28243228

  8. Modulation transfer function characterization and modeling of a Scophony infrared scene projector

    Science.gov (United States)

    Schildwachter, Eric F.; Boreman, Glenn D.

    1991-11-01

    A Scophony-configuration infrared scene projector, consisting of a raster-scanned CO2 laser and an acoustooptic (AO) modulator, was characterized for modulation transfer function (MTF) performance. The MTF components considered in the model were the Gaussian beam input to the AO cell, the finite aperture of the scan mirror, the width of the detector in the image plane, the transfer function of the amplifier electronics, and a term caused by Bragg-angle detuning over the bandwidth of the AM video signal driving the AO cell. The finite bandwidth of the input video signal caused a spread in the Bragg angle required for maximum diffraction efficiency. In the Scophony configuration, a collimated laser beam enters the AO cell at only one particular angle, so a falloff of diffraction efficiency (and hence MTF) resulted as the modulation frequency was increased. The Bragg-angle detuning term was found to dominate the measured system MTF.

  9. Modulation of acetylcholine receptor channel by a polar component isolated from toxic Ostreopsis lenticularis extracts.

    Science.gov (United States)

    Escalona De Motta, G; Mercado, J A; Tosteson, T R; González, I; Lasalde, J A

    1992-01-01

    Methanol extracts obtained from O. lenticularis clones are toxic to mice and inhibit acetylcholine-induced contractions in frog skeletal muscle. Chromatographic fractionation of extracts produced two major fractions with different retention times. Single channel recordings in myocyte membrane patches exposed to more polar fraction showed the appearance of acetylcholine-activated channels whose mean current amplitude was nearly half that of the controls. Channel open times under control and experimental conditions were similar. Thus, this dinoflagellate fraction reduces the ionic conductance of nicotinic receptor channels without altering their lifetime.

  10. ACC-FMD: ant colony clustering for functional module detection in protein-protein interaction networks.

    Science.gov (United States)

    Ji, Junzhong; Liu, Hongxin; Zhang, Aidong; Liu, Zhijun; Liu, Chunnian

    2015-01-01

    Mining functional modules in Protein-Protein Interaction (PPI) networks is a very important research for revealing the structure-functionality relationships in biological processes. More recently, some swarm intelligence algorithms have been successfully applied in the field. This paper presents a new nature-inspired approach, ACC-FMD, which is based on ant colony clustering to detect functional modules. First, some proteins with the higher clustering coefficients are, respectively, selected as ant seed nodes. And then, the picking and dropping operations based on ant probabilistic models are developed and employed to assign proteins into the corresponding clusters represented by seeds. Finally, the best clustering result in each generation is used to perform the information transmission by updating the similarly function. Experimental results on some benchmarked datasets show that ACC-FMD outperforms the CFinder and MCODE algorithms and has comparative performance with the MINE, COACH, DPClus and Core algorithms in terms of the general evaluation metrics.

  11. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

    NARCIS (Netherlands)

    Ottman, N.; Reunanen, J.; Meijerink, M.; Pietila, T.E.; Kainulainen, V.; Klievink, J.; Huuskonen, L.; Aalvink, S.; Skurnik, M.; Boeren, S.; Satokari, R.; Mercenier, A.; Palva, A.; Smidt, H.; Vos, W.M. De; Belzer, C.

    2017-01-01

    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont

  12. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

    NARCIS (Netherlands)

    Ottman, Noora; Reunanen, Justus; Meijerink, Marjolein; Pietila, Taija E.; Kainulainen, Veera; Klievink, Judith; Huuskonen, Laura; Aalvink, Steven; Skurnik, Mikael; Boeren, Sjef; Satokari, Reetta; Mercenier, Annick; Palva, Airi; Smidt, Hauke; Vos, de Willem M.; Belzer, Clara

    2017-01-01

    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont

  13. Identification and Structure-Function Study of Positive Allosteric Modulators of Kainate Receptors

    DEFF Research Database (Denmark)

    Larsen, Anja Probst; Fièvre, Sabine; Frydenvang, Karla

    2017-01-01

    Kainate receptors (KARs) consist of a class of ionotropic glutamate receptors, which exert diverse pre- and postsynaptic functions through complex signaling regulating the activity of neural circuits. Whereas numerous small-molecule positive allosteric modulators of the ligand-binding domain of (...

  14. Accuracy and uncertainty in random speckle modulation transfer function measurement of infrared focal plane arrays

    Science.gov (United States)

    Barnard, Kenneth J.; Jacobs, Eddie L.; Plummer, Philip J.

    2016-12-01

    This paper expands upon a previously reported random speckle technique for measuring the modulation transfer function of midwave infrared focal plane arrays by considering a number of factors that impact the accuracy of the estimated modulation transfer function. These factors arise from assumptions in the theoretical derivation and bias in the estimation procedure. Each factor is examined and guidelines are determined to maintain accuracy within 2% of the true value. The uncertainty of the measurement is found by applying a one-factor ANOVA analysis and confidence intervals are established for the results. The small magnitude of the confidence intervals indicates a very robust technique capable of distinguishing differences in modulation transfer function among focal plane arrays on the order of a few percent. This analysis directly indicates the high quality of the random speckle modulation transfer function measurement technique. The methodology is applied to a focal plane array and results are presented that emphasize the need for generating independent random speckle realizations to accurately assess measured values.

  15. Injection of a Phase Modulated Source into the Z-Beamlet Laser for Increased Energy Extraction.

    Energy Technology Data Exchange (ETDEWEB)

    Rambo, Patrick K.; Armstrong, Darrell J.; Schwarz, Jens; Smith, Ian C; Shores, Jonathon; Speas, Christopher; Porter, John L.

    2014-11-01

    The Z-Beamlet laser has been operating at Sandia National Laboratories since 2001 to provide a source of laser-generated x-rays for radiography of events on the Z-Accelerator. Changes in desired operational scope have necessitated the increase in pulse duration and energy available from the laser system. This is enabled via the addition of a phase modulated seed laser as an alternative front-end. The practical aspects of deployment are discussed here.

  16. Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.

    Directory of Open Access Journals (Sweden)

    Gongbo Li

    Full Text Available The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.

  17. Effects of Rhodomyrtus tomentosa extract on virulence factors of Candida albicans and human neutrophil function.

    Science.gov (United States)

    Hmoteh, Jutharat; Musthafa, Khadar Syed; Voravuthikunchai, Supayang Piyawan

    2017-12-10

    Candida albicans has become a major problem of oral candidiasis due to increase in antibiotic resistance. Rhodomyrtus tomentosa, a medicinal plant possessing several phytochemical constituents, has been considered as a potential source of antimicrobial and immunomodulatory agents. The aim of this study was to investigate anti-virulence and immunostimulatory activity of R. tomentosa ethanolic leaf extract against C. albicans. The effects of the extract on C. albicans were assessed on germ tube production, adherence of the organisms to surfaces, and biofilm. In addition, the effects of the extract on phagocytosis and killing activity of neutrophils against the pathogen were investigated. Suppression of germ tube production following 30 min exposure to the extract at 256 μg/mL was significantly increased in comparison with that of the unexposed cells (p extract at 512-1024 μg/mL significantly reduced biofilm forming ability of the organisms up to 42.31-64.58% (p extract at 256 μg/mL was observed (p extract at 50 μg/mL significantly enhanced phagocytosis and killing activity of neutrophils against the organism, compared with the control (p extract displayed a dual mode of action, inhibiting virulence factors of C. albicans and enhancing neutrophil functions. Further pharmaceutical development of the extract might be useful as an alternative therapeutic agent against oral candidiasis. Copyright © 2017. Published by Elsevier Ltd.

  18. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.

    Science.gov (United States)

    Browning, Kirsteen N; Travagli, R Alberto

    2014-10-01

    Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers.

  19. Graph coarse-graining reveals differences in the module-level structure of functional brain networks.

    Science.gov (United States)

    Kujala, Rainer; Glerean, Enrico; Pan, Raj Kumar; Jääskeläinen, Iiro P; Sams, Mikko; Saramäki, Jari

    2016-11-01

    Networks have become a standard tool for analyzing functional magnetic resonance imaging (fMRI) data. In this approach, brain areas and their functional connections are mapped to the nodes and links of a network. Even though this mapping reduces the complexity of the underlying data, it remains challenging to understand the structure of the resulting networks due to the large number of nodes and links. One solution is to partition networks into modules and then investigate the modules' composition and relationship with brain functioning. While this approach works well for single networks, understanding differences between two networks by comparing their partitions is difficult and alternative approaches are thus necessary. To this end, we present a coarse-graining framework that uses a single set of data-driven modules as a frame of reference, enabling one to zoom out from the node- and link-level details. As a result, differences in the module-level connectivity can be understood in a transparent, statistically verifiable manner. We demonstrate the feasibility of the method by applying it to networks constructed from fMRI data recorded from 13 healthy subjects during rest and movie viewing. While independently partitioning the rest and movie networks is shown to yield little insight, the coarse-graining framework enables one to pinpoint differences in the module-level structure, such as the increased number of intra-module links within the visual cortex during movie viewing. In addition to quantifying differences due to external stimuli, the approach could also be applied in clinical settings, such as comparing patients with healthy controls. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Modulation by Polypodium leucotomos extract of cytokine patterns in experimental trichomoniasis model

    OpenAIRE

    Nogal-Ruiz J.J.; Gómez-Barrio A.; Escario J.A.; Martínez-Fernández A.R.

    2003-01-01

    The immunomodulating effects of Anapsos®, an aqueous hydrosoluble extract obtained from the rhizomes of the fern Polypodium leucotomos, on both pathogenicity and cytokine levels in serum (IFN-γ/IL-4) were assayed in a Trichomonas vaginalis experimental model (BALB/c mice infected with 107 trichomonads and examined at day 15 after infection). Doses of 20 mg/kg/day administered for 10 days before the infection with the parasite induced a decrease of the experimental pathogenicity approximately...

  1. A binaural advantage in the subjective modulation transfer function with simple impulse responses

    DEFF Research Database (Denmark)

    Thompson, Eric Robert; Dau, Torsten

    2008-01-01

    The speech transmission index (STI) has been a popular method for predicting speech intelligibility in rooms. It is based on the magnitude of the modulation transfer function, which can be derived from the impulse response of the room and the background noise levels. However, it does not take...... to enhance the detectability of sinusoidal intensity modulations imposed on a broadband noise carrier and then convolved with simple, dichotic impulse responses. The results show that there can be a significant advantage to listening with two ears over listening with just one. Some further investigations...

  2. Perfusion information extracted from resting state functional magnetic resonance imaging.

    Science.gov (United States)

    Tong, Yunjie; Lindsey, Kimberly P; Hocke, Lia M; Vitaliano, Gordana; Mintzopoulos, Dionyssios; Frederick, Blaise deB

    2017-02-01

    It is widely known that blood oxygenation level dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) is an indirect measure for neuronal activations through neurovascular coupling. The BOLD signal is also influenced by many non-neuronal physiological fluctuations. In previous resting state (RS) fMRI studies, we have identified a moving systemic low frequency oscillation (sLFO) in BOLD signal and were able to track its passage through the brain. We hypothesized that this seemingly intrinsic signal moves with the blood, and therefore, its dynamic patterns represent cerebral blood flow. In this study, we tested this hypothesis by performing Dynamic Susceptibility Contrast (DSC) MRI scans (i.e. bolus tracking) following the RS scans on eight healthy subjects. The dynamic patterns of sLFO derived from RS data were compared with the bolus flow visually and quantitatively. We found that the flow of sLFO derived from RS fMRI does to a large extent represent the blood flow measured with DSC. The small differences, we hypothesize, are largely due to the difference between the methods in their sensitivity to different vessel types. We conclude that the flow of sLFO in RS visualized by our time delay method represents the blood flow in the capillaries and veins in the brain.

  3. Modulation of the antioxidant/pro-oxidant balance, cytotoxicity and antiviral actions of grape seed extracts.

    Science.gov (United States)

    Ignea, Codruţa; Dorobanţu, Cristina Mihaela; Mintoff, Christopher Paul; Branza-Nichita, Norica; Ladomery, Michael R; Kefalas, Panagiotis; Chedea, Veronica Sanda

    2013-12-15

    Grape seed extracts (GSEs) were investigated in yeast cells harbouring defects in their antioxidant system (regarding the cellular growth and growth recovery from H2O2 insult). GSEs antioxidant activity was detected in wild-type and mutant strains Δcta1, Δgsh1 and Δoye2glr1, while pro-oxidant activity in Δsod1 cells was seen. Assessment of proliferation of prostate cancer PC3 and HBV-replicating HepG2 2.2.15 cells treated with GSEs has shown higher cytotoxicity of red grape seed extract (RW) than white grape seed extract (WW) subjective to dose and period of administration. No antiviral effect was detected by measuring the secreted virion particles in HepG2 2.2.15 cells treated with GSEs. The GSEs play a dual antioxidant/pro-oxidant role in vivo according with the cellular antioxidant system deficiencies and exhibit cytotoxic properties in PC3 and HepG2 2.2.15 cell lines, but no antiviral action against HBV. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Extracting the time domain Green's function from ocean ambient noise using acoustic vector sensors.

    Science.gov (United States)

    Zhou, Jianbo; Piao, Shengchun; Qu, Ke; Iqbal, Kashif; Dong, Yang; Zhang, Shizhao; Zhang, Haigang; Wang, Xiaohan; Liu, Yaqin

    2017-11-01

    A function that closely resembles the two-point time-domain Green's function (TDGF) representing the time delays associated with multipath between the two sensors can be recovered by correlating the noise field measured by two sensors. Here, a technique for extracting the TDGF from ambient ocean noise using acoustic vector sensors is presented. Experimental results suggest that the averaging time to extract TDGF is greatly reduced if sound pressure sensors (hydrophones) are replaced by acoustic vector sensors. The direct arrival and bottom bounce arrival were extracted successfully with only 1 min of vertical velocity data, while the bottom bounce arrival was not extracted with even 10 min of sound pressure data.

  5. Crocus sativus, Serenoa repens and Pinus massoniana extracts modulate inflammatory response in isolated rat prostate challenged with LPS.

    Science.gov (United States)

    Chiavaroli, A; Recinella, L; Ferrante, C; Locatelli, M; Carradori, S; Macchione, N; Zengin, G; Leporini, L; Leone, S; Martinotti, S; Brunetti, L; Vacca, M; Menghini, L; Orlando, G

    Prostatitis is a common prostate disease that could be promoted by bacterial or non-bacterial infectious agents. In addition, inflammatory pathways involved in prostatitis have been increasingly studied, and herbal extracts endowed with anti-inflammatory effects are under investigation, individually or in combination, for their efficacy in alleviating the burden of inflammation, with possible improvements in symptoms. Serenoa repens (Serenoa), in combination with Crocus sativus (Crocus) and Pinus massoniana (Pinus), has previously shown to improve sexual function and limit urinary symptoms in patients suffering from concomitant erectile dysfunction and lower urinary tract symptoms. In this context, the aim of the present study is to evaluate the efficacy of Serenoa, Crocus and Pinus extracts, either alone or in combination, on immortalized prostate cells (PC3) and in an experimental model of bacterial prostatitis constituted by ex vivo prostate specimens challenged with lipopolysaccharide (LPS). We found that the tested extracts were able to reduce ROS production by PC3 cells and NFkB and PGE2 activity in prostate specimens challenged with LPS. In addition, the pharmacological association of the extracts displayed synergistic effects indicating a rational use of the mixture of the tested extracts as a novel anti-oxidant and anti-inflammatory formulation in bacterial prostatitis. Finally, we performed analytical and in vitro evaluation to better characterize the phytochemical profile and the mechanism of action of selected secondary metabolites.

  6. Alcoholic Extract of Ashwagandha Leaves Protects Against Amnesia by Regulation of Arc Function.

    Science.gov (United States)

    Gautam, Akash; Kaul, Sunil C; Thakur, Mahendra K

    2016-04-01

    Our earlier report on scopolamine-induced amnesia and its improvement by pre-treatment with i-Extract (alcoholic extract of Ashwagandha leaf) suggested that the i-Extract mediated nootropic effect may involve neuronal immediate early gene, Arc. With a hypothesis that the i-Extract induced expression of Arc protein may cause augmentation in Arc function, we examined the effect of i-extract on a major function of Arc protein, i.e. F-actin expansion, using Arc antisense oligodeoxynucleotides (ODN). Stereotaxic infusion of Arc antisense ODN in the CA1 region of hippocampus decreased the level of Arc protein as demonstrated by immunoblotting. However, this decrease was attenuated when treated with i-Extract prior to infusion of Arc antisense ODN. We noted a significant decrease in the polymerization of F-actin during scopolamine-induced amnesia as well as Arc antisense ODN infusion that was restored rather enhanced when pre-treated with i-Extract in both the cases. We also compared the corresponding changes between CA1 (the infusion site) and CA3 (neighbouring site of infusion) regions of hippocampus, and found more pronounced effects in CA1 than in the CA3 region. The extent of F-actin polymerization, as revealed by changes in the dendritic spine architecture through Golgi staining, showed that both scopolamine as well as Arc antisense ODN disrupted the spine density and mushroom-shaped morphology that was again regained if pre-treated with i-Extract. In conclusion, the findings reveal that the Arc helps in polymerization of F-actin and subsequent changes in the morphology of dendritic spines after pre-treatment with i-Extract in scopolamine-induced amnesic mice, suggesting an important role of Arc in scopolamine-induced amnesia and its recovery by i-Extract.

  7. EXTRACT

    DEFF Research Database (Denmark)

    Pafilis, Evangelos; Buttigieg, Pier Luigi; Ferrell, Barbra

    2016-01-01

    The microbial and molecular ecology research communities have made substantial progress on developing standards for annotating samples with environment metadata. However, sample manual annotation is a highly labor intensive process and requires familiarity with the terminologies used. We have the...... and text-mining-assisted curation revealed that EXTRACT speeds up annotation by 15-25% and helps curators to detect terms that would otherwise have been missed.Database URL: https://extract.hcmr.gr/......., organism, tissue and disease terms. The evaluators in the BioCreative V Interactive Annotation Task found the system to be intuitive, useful, well documented and sufficiently accurate to be helpful in spotting relevant text passages and extracting organism and environment terms. Comparison of fully manual...

  8. Automatic extraction of gene/protein biological functions from biomedical text.

    Science.gov (United States)

    Koike, Asako; Niwa, Yoshiki; Takagi, Toshihisa

    2005-04-01

    With the rapid advancement of biomedical science and the development of high-throughput analysis methods, the extraction of various types of information from biomedical text has become critical. Since automatic functional annotations of genes are quite useful for interpreting large amounts of high-throughput data efficiently, the demand for automatic extraction of information related to gene functions from text has been increasing. We have developed a method for automatically extracting the biological process functions of genes/protein/families based on Gene Ontology (GO) from text using a shallow parser and sentence structure analysis techniques. When the gene/protein/family names and their functions are described in ACTOR (doer of action) and OBJECT (receiver of action) relationships, the corresponding GO-IDs are assigned to the genes/proteins/families. The gene/protein/family names are recognized using the gene/protein/family name dictionaries developed by our group. To achieve wide recognition of the gene/protein/family functions, we semi-automatically gather functional terms based on GO using co-occurrence, collocation similarities and rule-based techniques. A preliminary experiment demonstrated that our method has an estimated recall of 54-64% with a precision of 91-94% for actually described functions in abstracts. When applied to the PUBMED, it extracted over 190 000 gene-GO relationships and 150 000 family-GO relationships for major eukaryotes.

  9. Modulation of BK Channel Function by Auxiliary Beta and Gamma Subunits

    Science.gov (United States)

    Li, Q.; Yan, J.

    2016-01-01

    The large-conductance, Ca2+- and voltage-activated K+ (BK) channel is ubiquitously expressed in mammalian tissues and displays diverse biophysical or pharmacological characteristics. This diversity is in part conferred by channel modulation with different regulatory auxiliary subunits. To date, two distinct classes of BK channel auxiliary subunits have been identified: β subunits and γ subunits. Modulation of BK channels by the four auxiliary β (β1–β4) subunits has been well established and intensively investigated over the past two decades. The auxiliary γ subunits, however, were identified only very recently, which adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. This chapter will review the current understanding of BK channel modulation by auxiliary β and γ subunits, especially the latest findings. PMID:27238261

  10. Potential of extracts from Saponaria officinalis and Calendula officinalis to modulate in vitro rumen fermentation with respect to their content in saponins.

    Science.gov (United States)

    Budan, Alexandre; Bellenot, Denis; Freuze, Ingrid; Gillmann, Louisa; Chicoteau, Pierre; Richomme, Pascal; Guilet, David

    2014-01-01

    Saponins have the potential to favorably modulate rumen fermentation, but there is generally a lack of the chemical structures associated with the described effects. The activity of extracts from Calendula officinalis and Saponaria officinalis in the rumen was evaluated in vitro. The S. officinalis root extract, reduced CH₄ production by 8.5% and increased total VFA concentration by 25.2%. C. officinalis and S. officinalis root extracts and the S. officinalis aerial part extract decreased the acetate to propionate ratio from 8.6 to 17.4%, according to the extract. An HPLC-ELSD analysis indicated that the saponin content ranged from 43.6 to 57.6 mg/g of dry matter (DM) in the C. officinalis extracts and from 224.0 to 693.8 mg/g of DM in the S. officinalis extracts, expressed as the hederacoside C equivalent. Identification of the saponin compounds present in the extracts by HPLC-MS(n) suggested that the saponin profile modulated the biological activities, showing the importance of determining the structure of saponins when evaluating extracts.

  11. Efficient and accurate Greedy Search Methods for mining functional modules in protein interaction networks.

    Science.gov (United States)

    He, Jieyue; Li, Chaojun; Ye, Baoliu; Zhong, Wei

    2012-06-25

    Most computational algorithms mainly focus on detecting highly connected subgraphs in PPI networks as protein complexes but ignore their inherent organization. Furthermore, many of these algorithms are computationally expensive. However, recent analysis indicates that experimentally detected protein complexes generally contain Core/attachment structures. In this paper, a Greedy Search Method based on Core-Attachment structure (GSM-CA) is proposed. The GSM-CA method detects densely connected regions in large protein-protein interaction networks based on the edge weight and two criteria for determining core nodes and attachment nodes. The GSM-CA method improves the prediction accuracy compared to other similar module detection approaches, however it is computationally expensive. Many module detection approaches are based on the traditional hierarchical methods, which is also computationally inefficient because the hierarchical tree structure produced by these approaches cannot provide adequate information to identify whether a network belongs to a module structure or not. In order to speed up the computational process, the Greedy Search Method based on Fast Clustering (GSM-FC) is proposed in this work. The edge weight based GSM-FC method uses a greedy procedure to traverse all edges just once to separate the network into the suitable set of modules. The proposed methods are applied to the protein interaction network of S. cerevisiae. Experimental results indicate that many significant functional modules are detected, most of which match the known complexes. Results also demonstrate that the GSM-FC algorithm is faster and more accurate as compared to other competing algorithms. Based on the new edge weight definition, the proposed algorithm takes advantages of the greedy search procedure to separate the network into the suitable set of modules. Experimental analysis shows that the identified modules are statistically significant. The algorithm can reduce the

  12. Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Leenders, Geert J.; Smeets, Mirjam B.; van den Boomen, Maaike; Berben, Monique; Nabben, Miranda; van Strijp, Dianne; Strijkers, Gustav J.; Prompers, Jeanine J.; Arslan, Fatih; Nicolay, Klaas; Vandoorne, Katrien

    2018-01-01

    Objective The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we

  13. Nuclear Effects in Extraction of Polarized Structure Functions of the Neutron at Large x

    Science.gov (United States)

    Maheswari, Dhiraj; Sargsian, Misak

    2017-09-01

    Currently there are active experimental efforts to extract the deep inelastic polarized structure functions of neutron from experiments in which polarized electron scatters off the polarized deuteron or 3He target. Special emphasize in these experiments is given to the large Bjorken x region where predictions of different QCD models largely diverge. The extraction of the neutron structure functions at large Bjorken x from nuclear DIS data is very sensitive to nuclear effects due to the correspondence of the large x region to the large internal momenta of bound nucleon in the nucleus. To account for these nuclear effects, we developed a theoretical approach for calculation of nuclear DIS scattering based on light-front approximation which allows to account for the relativistic effects of bound nucleon motion in the self consistent way. We present the model and the extraction of the polarized neutron DIS structure functions from the existing deuteron and 3He data. Supported by US Department of Energy Grant.

  14. Cottage cheeses functionalized with fennel and chamomile extracts: Comparative performance between free and microencapsulated forms.

    Science.gov (United States)

    Caleja, Cristina; Ribeiro, Andreia; Barros, Lillian; Barreira, João C M; Antonio, Amilcar L; Beatriz P P Oliveira, M; Barreiro, Maria Filomena; Ferreira, Isabel C F R

    2016-05-15

    Globally, there is a trend for healthy food products, preferably incorporating natural bioactive ingredients, replacing synthetic additives. From previous screening studies, extracts of Foeniculum vulgare Mill. (fennel) and Matricaria recutita L. (chamomile) maintained nutritional properties and improved the antioxidant activity of cottage cheese. Nevertheless, this effect was limited to 7 days. Accordingly, aqueous extracts of these plants were microencapsulated in alginate and incorporated into cottage cheese to achieve an extended bioactivity. Plain cottage cheese, and cheese functionalized by direct addition of free decoctions, were prepared and compared. Independently of plant species, "functionalization type" factor did not show a significant effect on the nutritional parameters, as also confirmed in the linear discriminant analysis, where these parameters were not selected as discriminating variables. Furthermore, samples functionalized with microencapsulated extracts showed higher antioxidant activity after the 7th day, thereby demonstrating that the main purpose of this experimental work was achieved. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Posidonia oceanica (L. Delile Ethanolic Extract Modulates Cell Activities with Skin Health Applications

    Directory of Open Access Journals (Sweden)

    Laura Cornara

    2018-01-01

    Full Text Available Seagrasses are high plants sharing adaptive metabolic features with both terrestrial plants and marine algae, resulting in a phytocomplex possibly endowed with interesting biological properties. The aim of this study is to evaluate the in vitro activities on skin cells of an ethanolic extract obtained from the leaves of Posidonia oceanica (L. Delile, family Potamogetonaceae, herein named Posidonia ethanolic extract (PEE. PEE showed high radical scavenging activity, high phenolic content, and resulted rich in chicoric acid, as determined through HPLC-MS analysis. The use of MTT assay on fibroblasts showed a PEE cytotoxicity threshold (IC05 of 50 µg/mL at 48 h, while a sub-toxic dose of 20 µg/mL induced a significant increase of fibroblast growth rate after 10 days. In addition, an ELISA assay revealed that PEE doses of 5 and 10 µg/mL induced collagen production in fibroblasts. PEE induced dose-dependent mushroom tyrosinase inhibition, up to about 45% inhibition at 1000 µg/mL, while 50% reduction of melanin was observed in melanoma cells exposed to 50 µg/mL PEE. Finally, PEE lipolytic activity was assessed by measuring glycerol release from adipocytes following triglyceride degradation. In conclusion, we have collected new data about the biological activities of the phytocomplex of P. oceanica seagrass on skin cells. Our findings indicate that PEE could be profitably used in the development of products for skin aging, undesired hyperpigmentation, and cellulite.

  16. Hair Follicle Plasticity with Complemented Immune-modulation Following Follicular Unit Extraction

    Science.gov (United States)

    Azar, Reza P; Thomas, Alexander H; Lindner, Gerd

    2015-01-01

    Background: During hair transplantation as an effective therapy for androgenetic alopecia, hair follicles were typically trans-located from the nonaffected occipital to the balding frontal or vertex region of the scalp. Although this is an autologous intervention, the donor and recipient hair follicle tissue differ in composition and local environment. Settings and Design: In two case studies, we investigated the changes in hair follicle morphology and the immune status of scalp and body hair follicles from different origins transplanted to the eyebrows and the frontal scalp using follicular unit extraction. Results: Quantitative histomorphometry and immunohistochemistry revealed a transformation in hair follicle length and dermal papilla size of the scalp, chest and beard hair follicles, which had been re-extracted after a 6-month period posttransplantation. Furthermore, a significant infiltration of B and T lymphocytes as well as macrophages could be observed most prominently in the infundibulum of transplanted hair follicles. Conclusion: The presented results demonstrate that hair follicle units from different body sites are capable to replace miniaturized or degraded hair follicles in different recipient areas like scalp or eyebrows as they keep their intrinsic capability or acquire the potential to readjust plastically within the beneficiary skin region. The essential secretory crosstalk underlying the observed tissue remodeling is possibly mediated by the infiltrating immune cells. PMID:25878444

  17. Full gate voltage range Lambert-function based methodology for FDSOI MOSFET parameter extraction

    Science.gov (United States)

    Karatsori, T. A.; Theodorou, C. G.; Ioannidis, E. G.; Haendler, S.; Josse, E.; Dimitriadis, C. A.; Ghibaudo, G.

    2015-09-01

    A new full gate voltage range methodology using a Lambert W function based inversion charge model, for extracting the electrical parameters in FDSOI nano-MOSFET devices, has been developed. Split capacitance-voltage measurements carried out on 14 nm technology FDSOI devices show that the inversion charge variation with gate voltage can be well described by a Lambert W function. Based on the drain current equation in the linear region including the inversion charge described by the Lambert function of gate voltage and the standard mobility equation enables five electrical MOSFET parameters to be extracted from experimental Id-Vg measurements (ideality factor, threshold voltage, low field mobility, first and second order mobility attenuation factors). The extracted parameters were compared with those extracted by the well-known Y-function in strong inversion region. The present methodology for extracting the electrical MOSFET parameters was verified over a wide range of channel lengths on nano-scale FDSOI devices, demonstrating its simplicity, accuracy and robustness.

  18. Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

    2017-12-15

    Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM

  19. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

    Directory of Open Access Journals (Sweden)

    Kishore Polireddy

    Full Text Available ABCB6 is a member of the adenosine triphosphate (ATP-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS, can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

  20. Supercritical Carbon Dioxide and Microwave-Assisted Extraction of Functional Lipophilic Compounds from Arthrospira platensis

    Science.gov (United States)

    Esquivel-Hernández, Diego A.; López, Víctor H.; Rodríguez-Rodríguez, José; Alemán-Nava, Gibrán S.; Cuéllar-Bermúdez, Sara P.; Rostro-Alanis, Magdalena; Parra-Saldívar, Roberto

    2016-01-01

    Arthrospira platensis biomass was used in order to obtain functional lipophilic compounds through green extraction technologies such as supercritical carbon dioxide fluid extraction (SFE) and microwave-assisted extraction (MAE). The temperature (T) factor was evaluated for MAE, while for SFE, pressure (P), temperature (T), and co-solvent (ethanol) (CS) were evaluated. The maximum extraction yield of the obtained oleoresin was (4.07% ± 0.14%) and (4.27% ± 0.10%) for SFE and MAE, respectively. Extracts were characterized by gas chromatography mass spectrometry (GC-MS) and gas chromatography flame ionization detector (GC-FID). The maximum contents of functional lipophilic compounds in the SFE and MAE extracts were: for carotenoids 283 ± 0.10 μg/g and 629 ± 0.13 μg/g, respectively; for tocopherols 5.01 ± 0.05 μg/g and 2.46 ± 0.09 μg/g, respectively; and for fatty acids 34.76 ± 0.08 mg/g and 15.88 ± 0.06 mg/g, respectively. In conclusion, the SFE process at P 450 bar, T 60 °C and CS 53.33% of CO2 produced the highest yield of tocopherols, carotenoids and fatty acids. The MAE process at 400 W and 50 °C gives the best extracts in terms of tocopherols and carotenoids. For yield and fatty acids, the MAE process at 400 W and 70 °C produced the highest values. Both SFE and MAE showed to be suitable green extraction technologies for obtaining functional lipophilic compounds from Arthrospira platensis. PMID:27164081

  1. Supercritical Carbon Dioxide and Microwave-Assisted Extraction of Functional Lipophilic Compounds from Arthrospira platensis

    Directory of Open Access Journals (Sweden)

    Diego A. Esquivel-Hernández

    2016-05-01

    Full Text Available Arthrospira platensis biomass was used in order to obtain functional lipophilic compounds through green extraction technologies such as supercritical carbon dioxide fluid extraction (SFE and microwave-assisted extraction (MAE. The temperature (T factor was evaluated for MAE, while for SFE, pressure (P, temperature (T, and co-solvent (ethanol (CS were evaluated. The maximum extraction yield of the obtained oleoresin was (4.07% ± 0.14% and (4.27% ± 0.10% for SFE and MAE, respectively. Extracts were characterized by gas chromatography mass spectrometry (GC-MS and gas chromatography flame ionization detector (GC-FID. The maximum contents of functional lipophilic compounds in the SFE and MAE extracts were: for carotenoids 283 ± 0.10 μg/g and 629 ± 0.13 μg/g, respectively; for tocopherols 5.01 ± 0.05 μg/g and 2.46 ± 0.09 μg/g, respectively; and for fatty acids 34.76 ± 0.08 mg/g and 15.88 ± 0.06 mg/g, respectively. In conclusion, the SFE process at P 450 bar, T 60 °C and CS 53.33% of CO2 produced the highest yield of tocopherols, carotenoids and fatty acids. The MAE process at 400 W and 50 °C gives the best extracts in terms of tocopherols and carotenoids. For yield and fatty acids, the MAE process at 400 W and 70 °C produced the highest values. Both SFE and MAE showed to be suitable green extraction technologies for obtaining functional lipophilic compounds from Arthrospira platensis.

  2. Soy-Leaf Extract Exerts Atheroprotective Effects via Modulation of Krüppel-Like Factor 2 and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    Jong-Min Han

    2017-02-01

    Full Text Available Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL in human umbilical vein endothelial cells (HUVECs and high-cholesterol diet (HCD-fed low-density lipoprotein receptor deficient (LDLR−/− mice. ESL induced the expression of Krüppel-like factor 2 (KLF2, an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS, and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α-stimulated HUVECs but also in 7-ketocholesterol (7-KC-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR−/− mice by 46% (p < 0.01 compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1, TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9, and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced atherosclerosis effectively.

  3. Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats.

    Science.gov (United States)

    Sahu, Surajit; Ray, Koushik; Yogendra Kumar, M S; Gupta, Shilpa; Kauser, Hina; Kumar, Sanjeev; Mishra, Kshipra; Panjwani, Usha

    2012-07-15

    The present study was performed to investigate the effects of Valeriana wallichi (VW) aqueous root extract on sleep-wake profile and level of brain monoamines on Sprague-Dawley rats. Electrodes and transmitters were implanted to record EEG and EMG in freely moving condition and the changes were recorded telemetrically after oral administration of VW in the doses of 100, 200 and 300 mg/kg body weight. Sleep latency was decreased and duration of non-rapid eye movement (NREM) sleep was increased in a dose dependent manner. A significant decrease of sleep latency and duration of wakefulness were observed with VW at doses of 200 and 300 mg/kg. Duration of NREM sleep as well as duration of total sleep was increased significantly after treatment with VW at the doses of 200 and 300 mg/kg. VW also increased EEG slow wave activity during NREM sleep at the doses of 200 and 300 mg/kg. Level of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and hydroxy indole acetic acid (HIAA) were measured in frontal cortex and brain stem after VW treatment at the dose of 200mg/kg. NE and 5HT level were decreased significantly in both frontal cortex and brain stem. DA and HIAA level significantly decreased only in cortex. DOPAC level was not changed in any brain region studied. In conclusion it can be said that VW water extract has a sleep quality improving effect which may be dependent upon levels of monoamines in cortex and brainstem. Copyright © 2012 Elsevier GmbH. All rights reserved.

  4. The relative efficacy of functional and developmental cranial modules for reconstructing global human population history.

    Science.gov (United States)

    von Cramon-Taubadel, Noreen

    2011-09-01

    This study tests the relative efficacy of human cranial modules, defined on the basis of developmental and functional criteria, for reconstructing neutral genetic population history. Specifically, two hypotheses were tested: 1) The "basicranial hypothesis" predicts that the endochondrally ossifying basicranium will be more reliable for reconstructing population history than intramembranously ossifying regions of the human cranium. This is based on the assumption that early ossification of the basicranium and its distinct functional constraints produce a cranial structure that is relatively immune to non-neutral evolutionary forces. 2) The "single function hypothesis" predicts that cranial regions associated with a single (sensory) function are less reliable indicators of neutral genetic history. Here the prediction is based on the logic that complex, multi-functional, integrated cranial regions are less likely toexhibit homoplasy and, therefore, provide a more accurate morphological proxy for genetic relationships. The congruence between craniometric affinity matrices and neutral genetic population matrices based on autosomal microsatellite and classical markers was assessed using a series of Mantel and Dow-Cheverud tests. The results did not support the predictions of the "basicranial hypothesis," as the endochondrally ossifying basicranium was not significantly more congruent with the genetic data than intramembraneously ossifying modules. Moreover, although the results provided some support for the "single function hypothesis," defining cranial modules on the basis of anatomical or functional complexity did not provide a consistent means of predicting their phylogenetic efficacy. These results have important implications for building an accurate inference model of cranial evolution in the human fossil record. 2011 Wiley-Liss, Inc.

  5. Functional brain asymmetry, attentional modulation, and interhemispheric transfer in boys with Tourette syndrome

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Lundervold, Arvid; Grüner, Renate

    2007-01-01

    on the right ear stimulus in the dichotic listening situation is thought to involve the same prefrontal attentional and executive functions that are involved in the suppression of tics, whereas, performance when focusing attention on the left ear stimulus additionally involves a callosal transfer...... to shift attention normally when instructed to focus on the right ear stimulus. When instructed to focus attention on the left ear stimulus, however, performance deteriorated in the TS group. Correlations with CC area further supported the hypothesized presence of deviant callosal functioning in the TS......We tested the hypothesis that children with Tourette syndrome (TS) would exhibit aberrant brain lateralization compared to a healthy control (HC) group in an attention-modulation version of a verbal dichotic listening task using consonant-vowel syllables. The modulation of attention to focus...

  6. Carpobrotus edulis methanol extract inhibits the MDR efflux pumps, enhances killing of phagocytosed S. aureus and promotes immune modulation.

    Science.gov (United States)

    Ordway, Diane; Hohmann, Judit; Viveiros, Miguel; Viveiros, Antonio; Molnar, Joseph; Leandro, Clara; Arroz, Maria Jorge; Gracio, Maria Amelia; Amaral, Leonard

    2003-05-01

    Although alkaloids from the family Aizoaceae have anticancer activity, species of this family have received little attention. Because these alkaloids also exhibit properties normally associated with compounds that have activity at the level of the plasma membrane, a methanol extract of Carpobrotus edulis, a common plant found along the Portuguese coast, was studied for properties normally associated with plasma membrane active compounds. The results of this study show that the extract is non-toxic at concentrations that inhibit a verapamil sensitive efflux pump of L5178 mouse T cell lymphoma cell line thereby rendering these multi-drug resistant cells susceptible to anticancer drugs. These non-toxic concentrations also prime THP-1 human monocyte-derived macrophages to kill ingested Staphylococcus aureus and to promote the release of lymphokines associated with cellular immune functions. The extract also induces the proliferation of THP-1 cells within 1 day of exposure to quantities normally associated with phytohaemagglutinin. The potential role of the compound(s) isolated from this plant in cancer biology is intriguing and is currently under investigation. It is supposed that the resistance modifier and immunomodulatory effect of this plant extract can be exploited in the experimental chemotherapy of cancer and bacterial or viral infections. Copyright 2003 John Wiley & Sons, Ltd.

  7. Macleaya cordata Extract Decreased Diarrhea Score and Enhanced Intestinal Barrier Function in Growing Piglets

    Directory of Open Access Journals (Sweden)

    Gang Liu

    2016-01-01

    Full Text Available Macleaya cordata extract is of great scientific and practical interest to researchers, due to its antimicrobial and anti-inflammatory responses within experimental animals. This study was designed to determine the diarrhea score and innate immunity of growing piglets after they had received Macleaya cordata extract supplements. A total of 240 growing pigs were randomly assigned to one of three dietary treatments, with 8 replicates per treatment and 10 piglets per replicate. All pigs received a basal diet containing similar amounts of nutrients. The three treatments were a control (no additive, an antibiotic (200 mg/kg colistin, and the Macleaya cordata extract supplement group (40 mg/kg Macleaya cordata extract. The diarrhea score was calculated after D 28. The jejunal samples were obtained from five piglets selected randomly from each treatment on D 28. In comparison with the control group, the dietary Macleaya cordata extract and colistin group demonstrated a substantially decreased diarrhea score. The introduction of Macleaya cordata extract supplements to the diet significantly increased volumes of ZO-1 and claudin-1, particularly in comparison with the pigs in the control group (P<0.05. The findings indicate that Macleaya cordata extract does enhance intestinal barrier function in growing piglets and that it could be used as a viable substitute for antibiotics.

  8. Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

    Science.gov (United States)

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

  9. Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

    Science.gov (United States)

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

  10. Sesame seed lignans: potent physiological modulators and possible ingredients in functional foods & nutraceuticals.

    Science.gov (United States)

    Kamal-Eldin, Afaf; Moazzami, Ali; Washi, Sidiga

    2011-01-01

    Sesame seed contains very high levels (up to 2.5%) of furofuran lignans with beneficial physiological activities, mainly sesamin, sesamolin, and sesaminol glucosides. Reported activities of sesame seed lignans include inter alias modulation of fatty acid metabolism, inhibition of cholesterol absorption and biosynthesis, antioxidant and vitamin E-sparing effects, hypotensive effects, improvement of liver functions in connection with alcohol metabolism, and antiaging effects. This review comprehends patents pertinent to the preparations and uses of sesame seed lignans in health promotion.

  11. Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice

    OpenAIRE

    Abad,Cesar Cavinato Cal; do Nascimento, Ademir Manuel; dos Santos, Leandro Eziquiel; Figueroa, Diego; Ramona, Pamella; Sartori, Michele; Scapini, Katia B.; Albuquerque, Oscar; Moraes-Silva,Ivana Cinthya; Coelho-J?nior, H?lio Jos?; Rodrigues,Bruno; Mostarda,Cristiano Teixeira; De Angelis, K?tia; Irigoyen, Maria Cl?udia

    2017-01-01

    The present study aimed to compare the effects of moderate-intensity continuous and high-intensity interval exercise training (ET) on exercise tolerance, cardiac morphometry and function, hemodynamic, and cardiac autonomic modulation in myocardial infarcted mice. Wild-type mice (WT) were divided into four groups: sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium infarction underwent to moderate-intensity continuous ET (MICT), and WT myocardium infarction underwent to hi...

  12. Efficient α, β-motif finder for identification of phenotype-related functional modules

    Directory of Open Access Journals (Sweden)

    Schmidt Matthew C

    2011-11-01

    Full Text Available Abstract Background Microbial communities in their natural environments exhibit phenotypes that can directly cause particular diseases, convert biomass or wastewater to energy, or degrade various environmental contaminants. Understanding how these communities realize specific phenotypic traits (e.g., carbon fixation, hydrogen production is critical for addressing health, bioremediation, or bioenergy problems. Results In this paper, we describe a graph-theoretical method for in silico prediction of the cellular subsystems that are related to the expression of a target phenotype. The proposed (α, β-motif finder approach allows for identification of these phenotype-related subsystems that, in addition to metabolic subsystems, could include their regulators, sensors, transporters, and even uncharacterized proteins. By comparing dozens of genome-scale networks of functionally associated proteins, our method efficiently identifies those statistically significant functional modules that are in at least α networks of phenotype-expressing organisms but appear in no more than β networks of organisms that do not exhibit the target phenotype. It has been shown via various experiments that the enumerated modules are indeed related to phenotype-expression when tested with different target phenotypes like hydrogen production, motility, aerobic respiration, and acid-tolerance. Conclusion Thus, we have proposed a methodology that can identify potential statistically significant phenotype-related functional modules. The functional module is modeled as an (α, β-clique, where α and β are two criteria introduced in this work. We also propose a novel network model, called the two-typed, divided network. The new network model and the criteria make the problem tractable even while very large networks are being compared. The code can be downloaded from http://www.freescience.org/cs/ABClique/

  13. Immunomodulatory effects of Santolina chamaecyparissus leaf extracts on human neutrophil functions.

    Science.gov (United States)

    Boudoukha, Chahra; Bouriche, Hamama; Ortega, Eduardo; Senator, Abderrahmane

    2016-01-01

    Santolina chamaecyparissus L. (Asteraceae) is an aromatic plant wide spread in the Mediterranean region. It is used in folk medicine for its anti-inflammatory properties. The effects of S. chamaecyparissus aqueous extract (SCAE) and polyphenolic extract (SCPE) on human polymorphonuclear neutrophil (PMN) degranulation, chemotaxis, phagocytosis, and microbicidal capacity were examined in vitro. Aqueous and polyphenolic extracts were prepared from S. chamaecyparissus leaves. The elastase release was used as a marker for measuring PMN degranulation, while chemotaxis was performed using a 48-microwell chemotaxis chamber. The phagocytosis and the microbicidal capacity were evaluated using fresh cultures of Candida albicans. The treatment of neutrophils with different concentrations (10-200 µg/ml) of SCAE and SCPE caused a significant (p functions support the anti-inflammatory activity and show new mechanisms of action and effectiveness of S. chamaecyparissus leaf extracts. This plant may be considered as an interesting source of anti-inflammatory and immunomodulatory agents.

  14. Functional Relations Modulate the Responsiveness to Affordances Despite the Impact of Conflicting Stimulus–Response Mappings

    Directory of Open Access Journals (Sweden)

    Roberta Vastano

    2017-11-01

    Full Text Available The study investigated how conflicting stimulus–response mappings influenced affordance processing given a manipulation of the functional relations. Participants performed a task involving consistent–inconsistent stimulus–response mappings: Implicit Relational Assessment Procedure (IRAP. They were instructed to confirm or to deny a relation between words and tool-objects (consistent blocks or to provide non-conventional responses (inconsistent blocks. The relations between stimuli could functionally match (e.g., Kitchen – Spatula or not (e.g., Kitchen – Hammer, as well as the spatial relations (e.g., a match or a mismatch between participants’ hand response and the tool-object orientation. The results showed faster reaction times (RTs when functional relations between stimuli matched both in consistent and inconsistent blocks. Differences in RTs and accuracy between consistent and inconsistent blocks were only found when the functional relation between stimuli matched. No modulation of the performance was observed for mismatching functional relations and spatial relations between blocks. These results support the hypothesis that the responsiveness to affordances is strongly modulated by matching functional relations, despite the impact of conflicting stimulus–response mappings.

  15. Functional Relations Modulate the Responsiveness to Affordances Despite the Impact of Conflicting Stimulus-Response Mappings.

    Science.gov (United States)

    Vastano, Roberta; Finn, Martin; Barnes-Holmes, Dermot

    2017-01-01

    The study investigated how conflicting stimulus-response mappings influenced affordance processing given a manipulation of the functional relations. Participants performed a task involving consistent-inconsistent stimulus-response mappings: Implicit Relational Assessment Procedure (IRAP). They were instructed to confirm or to deny a relation between words and tool-objects (consistent blocks) or to provide non-conventional responses (inconsistent blocks). The relations between stimuli could functionally match (e.g., Kitchen - Spatula) or not (e.g., Kitchen - Hammer), as well as the spatial relations (e.g., a match or a mismatch between participants' hand response and the tool-object orientation). The results showed faster reaction times (RTs) when functional relations between stimuli matched both in consistent and inconsistent blocks. Differences in RTs and accuracy between consistent and inconsistent blocks were only found when the functional relation between stimuli matched. No modulation of the performance was observed for mismatching functional relations and spatial relations between blocks. These results support the hypothesis that the responsiveness to affordances is strongly modulated by matching functional relations, despite the impact of conflicting stimulus-response mappings.

  16. Functional Relations Modulate the Responsiveness to Affordances Despite the Impact of Conflicting Stimulus–Response Mappings

    Science.gov (United States)

    Vastano, Roberta; Finn, Martin; Barnes-Holmes, Dermot

    2017-01-01

    The study investigated how conflicting stimulus–response mappings influenced affordance processing given a manipulation of the functional relations. Participants performed a task involving consistent–inconsistent stimulus–response mappings: Implicit Relational Assessment Procedure (IRAP). They were instructed to confirm or to deny a relation between words and tool-objects (consistent blocks) or to provide non-conventional responses (inconsistent blocks). The relations between stimuli could functionally match (e.g., Kitchen – Spatula) or not (e.g., Kitchen – Hammer), as well as the spatial relations (e.g., a match or a mismatch between participants’ hand response and the tool-object orientation). The results showed faster reaction times (RTs) when functional relations between stimuli matched both in consistent and inconsistent blocks. Differences in RTs and accuracy between consistent and inconsistent blocks were only found when the functional relation between stimuli matched. No modulation of the performance was observed for mismatching functional relations and spatial relations between blocks. These results support the hypothesis that the responsiveness to affordances is strongly modulated by matching functional relations, despite the impact of conflicting stimulus–response mappings. PMID:29163319

  17. Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.

    Science.gov (United States)

    Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

    2016-06-15

    Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A Novel Method to Detect Functional microRNA Regulatory Modules by Bicliques Merging.

    Science.gov (United States)

    Liang, Cheng; Li, Yue; Luo, Jiawei

    2016-01-01

    MicroRNAs (miRNAs) are post-transcriptional regulators that repress the expression of their targets. They are known to work cooperatively with genes and play important roles in numerous cellular processes. Identification of miRNA regulatory modules (MRMs) would aid deciphering the combinatorial effects derived from the many-to-many regulatory relationships in complex cellular systems. Here, we develop an effective method called BiCliques Merging (BCM) to predict MRMs based on bicliques merging. By integrating the miRNA/mRNA expression profiles from The Cancer Genome Atlas (TCGA) with the computational target predictions, we construct a weighted miRNA regulatory network for module discovery. The maximal bicliques detected in the network are statistically evaluated and filtered accordingly. We then employed a greedy-based strategy to iteratively merge the remaining bicliques according to their overlaps together with edge weights and the gene-gene interactions. Comparing with existing methods on two cancer datasets from TCGA, we showed that the modules identified by our method are more densely connected and functionally enriched. Moreover, our predicted modules are more enriched for miRNA families and the miRNA-mRNA pairs within the modules are more negatively correlated. Finally, several potential prognostic modules are revealed by Kaplan-Meier survival analysis and breast cancer subtype analysis. BCM is implemented in Java and available for download in the supplementary materials, which can be found on the Computer Society Digital Library at http://doi.ieeecomputersociety.org/10.1109/ TCBB.2015.2462370.

  19. Effects of aqueous extract of Musa paradisiaca root on testicular function parameters of male rats.

    Science.gov (United States)

    Yakubu, Musa Toyin; Oyeyipo, Theo Oyetayo; Quadri, Ayodeji Luqman; Akanji, Musbau Adewumi

    2013-01-01

    There is an age-long claim that the Musa paradisiaca root is used to manage reproductive dysfunction, most especially sexual dysfunction (as an aphrodisiac), but there are no data in the open scientific literature that have refuted or supported this claim and the effects of M. paradisiaca root on the testes. Therefore, this study was aimed at investigating the effect of oral administration of the aqueous extract of M. paradisiaca root on the testicular function parameters of male rat testes. Sexually matured male albino rats (138.67±5.29 g) were randomly assigned into four groups, A, B, C, and D, that respectively received 0.5 mL (3.6 mL/kg body weight) of distilled water and 25, 50, and 100 mg/kg body weight of the extract, orally, once daily, for 14 days. The extract significantly increased (pparadisiaca root extract at doses of 25, 50, and 100 mg/kg body weight enhanced the testosterone-dependent normal functioning of the testes. Overall, the aqueous extract of M. paradisiaca stimulated the normal functioning of the testes and exhibited both androgenic and anabolic properties. The results may explain the rationale behind the folkloric beneficial effect of the plant in the management of reproductive dysfunction.

  20. NCS-1 associates with adenosine A2A receptors and modulates receptor function

    Directory of Open Access Journals (Sweden)

    Gemma eNavarro

    2012-04-01

    Full Text Available Modulation of G protein-coupled receptor (GPCR signalling by local changes in intracellular calcium concentration is an established function of Calmodulin which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with calmodulin targets with different functional outcome. In the present study we aimed to investigate if a target of calmodulin – the A2A adenosine receptor, is able to associate with two other neuronal calcium binding proteins, namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer and co-immunoprecipitation experiments we show the existence of A2A - NCS-1 complexes in living cells whereas caldendrin did not associate with A2A receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A2A receptor intracellular signalling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signalling.

  1. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  2. Evolution of the class C GPCR Venus flytrap modules involved positive selected functional divergence.

    Science.gov (United States)

    Cao, Jianhua; Huang, Siluo; Qian, Ji; Huang, Jinlin; Jin, Li; Su, Zhixi; Yang, Ji; Liu, Jianfeng

    2009-03-27

    Class C G protein-coupled receptors (GPCRs) represent a distinct group of the GPCR family, which structurally possess a characteristically distinct extracellular domain inclusive of the Venus flytrap module (VFTM). The VFTMs of the class C GPCRs is responsible for ligand recognition and binding, and share sequence similarity with bacterial periplasmic amino acid binding proteins (PBPs). An extensive phylogenetic investigation of the VFTMs was conducted by analyzing for functional divergence and testing for positive selection for five typical groups of the class C GPCRs. The altered selective constraints were determined to identify the sites that had undergone functional divergence via positive selection. In order to structurally demonstrate the pattern changes during the evolutionary process, three-dimensional (3D) structures of the GPCR VFTMs were modelled and reconstructed from ancestral VFTMs. Our results show that the altered selective constraints in the VFTMs of class C GPCRs are statistically significant. This implies that functional divergence played a key role in characterizing the functions of the VFTMs after gene duplication events. Meanwhile, positive selection is involved in the evolutionary process and drove the functional divergence of the VFTMs. Our results also reveal that three continuous duplication events occurred in order to shape the evolutionary topology of class C GPCRs. The five groups of the class C GPCRs have essentially different sites involved in functional divergence, which would have shaped the specific structures and functions of the VFTMs. Taken together, our results show that functional divergence involved positive selection and is partially responsible for the evolutionary patterns of the class C GPCR VFTMs. The sites involved in functional divergence will provide more clues and candidates for further research on structural-function relationships of these modules as well as shedding light on the activation mechanism of the class C

  3. Evolution of the class C GPCR Venus flytrap modules involved positive selected functional divergence

    Directory of Open Access Journals (Sweden)

    Su Zhixi

    2009-03-01

    Full Text Available Abstract Background Class C G protein-coupled receptors (GPCRs represent a distinct group of the GPCR family, which structurally possess a characteristically distinct extracellular domain inclusive of the Venus flytrap module (VFTM. The VFTMs of the class C GPCRs is responsible for ligand recognition and binding, and share sequence similarity with bacterial periplasmic amino acid binding proteins (PBPs. An extensive phylogenetic investigation of the VFTMs was conducted by analyzing for functional divergence and testing for positive selection for five typical groups of the class C GPCRs. The altered selective constraints were determined to identify the sites that had undergone functional divergence via positive selection. In order to structurally demonstrate the pattern changes during the evolutionary process, three-dimensional (3D structures of the GPCR VFTMs were modelled and reconstructed from ancestral VFTMs. Results Our results show that the altered selective constraints in the VFTMs of class C GPCRs are statistically significant. This implies that functional divergence played a key role in characterizing the functions of the VFTMs after gene duplication events. Meanwhile, positive selection is involved in the evolutionary process and drove the functional divergence of the VFTMs. Our results also reveal that three continuous duplication events occurred in order to shape the evolutionary topology of class C GPCRs. The five groups of the class C GPCRs have essentially different sites involved in functional divergence, which would have shaped the specific structures and functions of the VFTMs. Conclusion Taken together, our results show that functional divergence involved positive selection and is partially responsible for the evolutionary patterns of the class C GPCR VFTMs. The sites involved in functional divergence will provide more clues and candidates for further research on structural-function relationships of these modules as well as

  4. Data-driven haemodynamic response function extraction using Fourier-wavelet regularised deconvolution

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    Roerdink Jos BTM

    2008-04-01

    Full Text Available Abstract Background We present a simple, data-driven method to extract haemodynamic response functions (HRF from functional magnetic resonance imaging (fMRI time series, based on the Fourier-wavelet regularised deconvolution (ForWaRD technique. HRF data are required for many fMRI applications, such as defining region-specific HRFs, effciently representing a general HRF, or comparing subject-specific HRFs. Results ForWaRD is applied to fMRI time signals, after removing low-frequency trends by a wavelet-based method, and the output of ForWaRD is a time series of volumes, containing the HRF in each voxel. Compared to more complex methods, this extraction algorithm requires few assumptions (separability of signal and noise in the frequency and wavelet domains and the general linear model and it is fast (HRF extraction from a single fMRI data set takes about the same time as spatial resampling. The extraction method is tested on simulated event-related activation signals, contaminated with noise from a time series of real MRI images. An application for HRF data is demonstrated in a simple event-related experiment: data are extracted from a region with significant effects of interest in a first time series. A continuous-time HRF is obtained by fitting a nonlinear function to the discrete HRF coeffcients, and is then used to analyse a later time series. Conclusion With the parameters used in this paper, the extraction method presented here is very robust to changes in signal properties. Comparison of analyses with fitted HRFs and with a canonical HRF shows that a subject-specific, regional HRF significantly improves detection power. Sensitivity and specificity increase not only in the region from which the HRFs are extracted, but also in other regions of interest.

  5. Extraction (DSX from Erigeron breviscapus modulates outward potassium currents in rat retinal ganglion cells

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    Shuo Yin

    2015-12-01

    Full Text Available AIM: To investigate the effect of DSX, an active component extracted from Erigeron breviscapus, on the voltage-gated outward K+ channel currents in rat retinal ganglion cells (RGCs by using electrophysiological method, and to explore the possible mechanisms of DSX on optic nerve protection. METHODS: Outward K+ currents were recorded by using whole-cell patch-clamp techniques on acutely isolated rat RGCs. Outward K+ currents were induced by a series of depolarizing voltage pulses from a holding potential of -70 mV to +20 mV in an increment of 10 mV. RESULTS: Extracellular application of DSX voltage-dependently suppressed both the steady-state and peak current amplitudes of outward K+ currents in rat RGCs. Furthermore, DSX reversibly and dose-dependently inhibited the amplitudes of outward K+ currents of the cells. At +20 mV membrane potential DSX at the concentrations of 0.02 g/L and 0.05 g/L showed no significant effects on the currents. In contrast, DSX at higher concentrations (0.1 g/L, 0.2 g/L and 0.5 g/L significantly suppressed the current amplitudes. CONCLUSION: These results suggest that DSX reversibly and dose-dependently suppress outward K+ channel currents in rat RGCs, which may be one of the possible mechanisms underlying Erigeron breviscapus prevents vision loss and RGC damage caused by glaucoma.

  6. The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

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    Marcel Stark

    2014-01-01

    Full Text Available The standardized Ginkgo biloba extract EGb 761 has well-described antioxidative activities and effects on different cytoprotective signaling pathways. Consequently, a potential use of EGb 761 in neurodegenerative diseases has been proposed. A common characteristic feature of a variety of such disorders is the pathologic formation of protein aggregates, suggesting a crucial role for protein homeostasis. In this study, we show that EGb 761 increased the catalytic activity of the proteasome and enhanced protein degradation in cultured cells. We further investigated this effect in a cellular model of Huntington’s disease (HD by employing cells expressing pathologic variants of a polyglutamine protein (polyQ protein. We show that EGb 761 affected these cells by (i increasing proteasome activity and (ii inducing a more efficient degradation of aggregation-prone proteins. These results demonstrate a novel activity of EGb 761 on protein aggregates by enhancing proteasomal protein degradation, suggesting a therapeutic use in neurodegenerative disorders with a disturbed protein homeostasis.

  7. Degradation of sulfated polysaccharide extracted from algal Laminaria japonica and its modulation on calcium oxalate crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang Jianming, E-mail: toyjm@jnu.edu.cn [Department of Chemistry, Jinan University, Guangzhou 510632 (China); Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632 (China); Wang Miao; Lu Peng; Tan Jin [Department of Chemistry, Jinan University, Guangzhou 510632 (China); Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632 (China)

    2010-08-30

    Sulfated polysaccharide (LPS) extracted from alga Laminaria japonica was degraded by hydrogen peroxide (H{sub 2}O{sub 2}). The average molecular weight of LPS was apparently decreased from 172,000 to 9550 after degradation, while the proportion of sulfate groups (-OSO{sub 3}{sup -}) and carboxylic groups (-COO{sup -}) in the molecular chains of LPS were slightly decreased from 4.5% and 5.20% to 3.9% and 4.64%, respectively. The effects of degraded and natural LPS on formation of calcium oxalate (CaOxa) crystals were investigated in vitro using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), zeta-potential, and atomic absorption spectroscopy. LPS could increase the concentration of soluble Ca{sup 2+} ions in the solution, decrease the weight of precipitated CaOxa, and increase the negative value of zeta-potential of CaOxa crystals. LPS also inhibits the formation of thermodynamically stable calcium oxalate monohydrate (COM) crystals, while inducing and stabilizing metastable calcium oxalate dihydrate (COD) crystals. These results suggested that both degraded and natural LPS could decrease CaOxa crystallization, but the inhibition efficiency of the degraded LPS was clearly superior to that of the natural LPS. We expected this investigation would provide encouragement for further exploration into new drugs for the prevention and treatment of urolithiasis.

  8. A charge-pump 60kV modulator for the ISOLDE target extraction voltage

    CERN Document Server

    Barlow, R A; Fowler, A; Gaudillet, H; Gharsa, T; Schipper, J

    2015-01-01

    The ISOLDE facility at CERN provides radioactive ion beams to a number of experimental stations. These ions are produced by a metal target, floating at 60 kV, which is impacted by a 1.4 GeV high intensity proton beam. The ions are then accelerated by a grounded extraction electrode to 60 keV, before transport to the experimental area. During proton beam impact extremely high ionisation of the volume around the target gives rise to significant leakage current which results in loss of charge on the effective target capacitance of approximately 6 nF. If short life-time isotopes are to be studied, the 60 kV must be re-established within a maximum of 10 ms. Recharging the target capacitance to 60 kV and to the required stability of better than 10-4 precludes a direct charging system and an alternative method of re-establishing the 60 kV is used. The present system [1], in operation since 1991, employs a resonant circuit which is triggered 35 µs prior to beam impact. This circuit transfers the charge on the effec...

  9. Bayesian extraction of the parton distribution amplitude from the Bethe-Salpeter wave function

    Science.gov (United States)

    Gao, Fei; Chang, Lei; Liu, Yu-xin

    2017-07-01

    We propose a new numerical method to compute the parton distribution amplitude (PDA) from the Euclidean Bethe-Salpeter wave function. The essential step is to extract the weight function in the Nakanishi representation of the Bethe-Salpeter wave function in Euclidean space, which is an ill-posed inversion problem, via the maximum entropy method (MEM). The Nakanishi weight function as well as the corresponding light-front parton distribution amplitude (PDA) can be well determined. We confirm prior work on PDA computations, which was based on different methods.

  10. Bayesian extraction of the parton distribution amplitude from the Bethe–Salpeter wave function

    Directory of Open Access Journals (Sweden)

    Fei Gao

    2017-07-01

    Full Text Available We propose a new numerical method to compute the parton distribution amplitude (PDA from the Euclidean Bethe–Salpeter wave function. The essential step is to extract the weight function in the Nakanishi representation of the Bethe–Salpeter wave function in Euclidean space, which is an ill-posed inversion problem, via the maximum entropy method (MEM. The Nakanishi weight function as well as the corresponding light-front parton distribution amplitude (PDA can be well determined. We confirm prior work on PDA computations, which was based on different methods.

  11. Efficient blood flow visualization using flowline extraction and opacity modulation based on vascular structure analysis.

    Science.gov (United States)

    Kwon, Ohjae; Lee, Jeongjin; Kim, Bohyoung; Shin, Juneseuk; Shin, Yeong-Gil

    2017-03-01

    With the recent advances regarding the acquisition and simulation of blood flow data, blood flow visualization has been widely used in medical imaging for the diagnosis and treatment of pathological vessels. In this paper, we present a novel method for the visualization of the blood flow in vascular structures. The vessel inlet or outlet is first identified using the orthogonality metric between the normal vectors of the flow velocity and vessel surface. Then, seed points are generated on the identified inlet or outlet by Poisson disk sampling. Therefore, it is possible to achieve the automatic seeding that leads to a consistent and faster flow depiction by skipping the manual location of a seeding plane for the initiation of the line integration. In addition, the early terminated line integration in the thin curved vessels is resolved through the adaptive application of the tracing direction that is based on the flow direction at each seed point. Based on the observation that blood flow usually follows the vessel track, the representative flowline for each branch is defined by the vessel centerline. Then, the flowlines are rendered through an opacity assignment according to the similarity between their shape and the vessel centerline. Therefore, the flowlines that are similar to the vessel centerline are shown transparently, while the different ones are shown opaquely. Accordingly, the opacity modulation method enables the flowlines with an unusual flow pattern to appear more noticeable, while the visual clutter and line occlusion are minimized. Finally, Hue-Saturation-Value color coding is employed for the simultaneous exhibition of flow attributes such as local speed and residence time. The experiment results show that the proposed technique is suitable for the depiction of the blood flow in vascular structures. The proposed approach is applicable to many kinds of tubular structures with embedded flow information. Copyright © 2017 Elsevier Ltd. All rights

  12. Evaluation of endoscopic vein extraction on structural and functional viability of saphenous vein endothelium

    OpenAIRE

    Hussaini, Bader E; Lu, Xiu-Gui; Wolfe, J Alan; Thatte, Hemant S

    2011-01-01

    Abstract Objectives Endothelial injury during harvest influences graft patency post CABG. We have previously shown that endoscopic harvest causes structural and functional damage to the saphenous vein (SV) endothelium. However, causes of such injury may depend on the extraction technique. In order to assess this supposition, we evaluated the effect of VirtuoSaph endoscopic SV harvesting technique (VsEVH) on structural and functional viability of SV endothelium using multiphoton imaging, bioch...

  13. Cichorium intybus root extract: A "vitamin D-like" active ingredient to improve skin barrier function.

    Science.gov (United States)

    Maia Campos, P M B G; G Mercurio, D; O Melo, M; Closs-Gonthier, B

    2017-02-01

    During the aging process, the human skin suffers many alterations including dryness, skin barrier function damage. The skin barrier function is important to the prevention of skin alterations and maintenance of homeostasis. So, the objective of this study was to assess the clinical efficacy on skin barrier function of Cichorium intybus root extract in cosmetic formulations with or without UV filters. Fifty women, aged between 45 and 60 years, were divided into two groups. One group received vehicle formulations containing UV filters, and the other group received formulations without UV filters. Both groups received a formulation containing the extract and the vehicle. The formulations were applied twice daily to the upper arms after washing with sodium lauryl sulphate. Transepidermal water loss (TEWL) and skin microrelief were evaluated before and after a 14- and 28-day period of treatment. The control regions and regions where the vehicles were applied showed an increase in the TEWL. For the formulations containing the extract, decreased TEWL and improved microrelief were observed when compared to the vehicle and control areas after a 28-day period. In conclusion, Cichorium intybus root extract showed protective and restructuring effects on the skin and stands out as an innovative ingredient to improve skin barrier function.

  14. Extraction, composition, and functional properties of dried alfalfa (Medicago sativa L.) leaf protein

    Science.gov (United States)

    Alfalfa, traditionally used for animal feed, has attracted attention as a potential feedstock for biofuels and the viability of the process would be enhanced by co-products with value-added uses. This study describes extraction of protein from dried alfalfa leaves and the functional properties of th...

  15. Characteristics of extraction and functionality of protein from tomato pomace produced with different industrial processing methods

    Science.gov (United States)

    The seeds from tomato pomace, a by-product of tomato processing, contains valuable but underutilized protein with unique functional properties. The objectives of this research were to study the impact of industrial hot and cold break tomato processing on protein extraction from defatted tomato seeds...

  16. Reconfigurable optical interleaver modules with tunable wavelength transfer matrix function using polymer photonics lightwave circuits.

    Science.gov (United States)

    Chen, Changming; Niu, Xiaoyan; Han, Chao; Shi, Zuosen; Wang, Xinbin; Sun, Xiaoqiang; Wang, Fei; Cui, Zhanchen; Zhang, Daming

    2014-08-25

    A transparent reconfigurable optical interleaver module composed of cascaded AWGs-based wavelength-channel-selector/interleaver monolithically integrated with multimode interference (MMI) variable optical attenuators (VOAs) and Mach-Zehnder interferometer (MZI) switch arrays was designed and fabricated using polymer photonic lightwave circuits. Highly fluorinated photopolymer and grafting modified organic-inorganic hybrid material were synthesized as the waveguide core and caldding, respectively. Thermo-optic (TO) tunable wavelength transfer matrix (WTM) function of the module can be achieved for optical routing network. The one-chip transmission loss is ~ 6 dB and crosstalk is less than ~25 dB for transverse-magnetic (TM) mode. The crosstalk and extinction ratio of the MMI VOAs were measured as -15.2 dB and 17.5 dB with driving current 8 mA, respectively. The modulation depth of the TO switches is obtained as ~18.2 dB with 2.2 V bias. Proposed novel interleaver module could be well suited for DWDM optical communication systems.

  17. Modulation of adipogenesis and glucose uptake by Curcuma longa extract in 3T3L1 and L6 cell lines - An in vitro study

    Directory of Open Access Journals (Sweden)

    A. Prathapan

    2012-05-01

    Full Text Available Objective: To evaluate the effects of ethyl acetate extract of Curcuma longa against modulation of glucose uptake and adipogenesis in cell line models. Methods: We used 3T3L1 and L6 cells to investigate cytotoxicity, glucose uptake with 2-NBDG as probe and adipogenesis. All the analysis was done with flowcytometry. Results: The results showed that the extract did not possess any significant glucose uptake activity but it exhibited significant adipocyte differentiation potential. Conclusions: Ethyl acetate extract of Curcuma longa exhibits significant antiadipogenesis and can be used as an effective drug for the treatment of obesity and other associated complications.

  18. Functional role for cortical-striatal circuitry in modulating alcohol self-administration.

    Science.gov (United States)

    Jaramillo, Anel A; Randall, Patrick A; Stewart, Spencer; Fortino, Brayden; Van Voorhies, Kalynn; Besheer, Joyce

    2018-03-01

    The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4D i -Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC→AcbC or IC→AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC→AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC→AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effects of Geum urbanum L. root extracts and its constituents on polymorphonuclear leucocytes functions. Significance in periodontal diseases.

    Science.gov (United States)

    Granica, Sebastian; Kłębowska, Agnieszka; Kosiński, Michał; Piwowarski, Jakub P; Dudek, Marta K; Kaźmierski, Sławomir; Kiss, Anna K

    2016-07-21

    containing the highest level of gemin A, have exerted similar but weaker activity. The modulating effect on the neutrophils function of extracts, and its main constituent gemin A, support the traditional use of this plant material in cavity inflammation including mucositis, gingivitis and periodontosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Papaya (Carica papaya) leaf methanolic extract modulates in vitro rumen methanogenesis and rumen biohydrogenation.

    Science.gov (United States)

    Jafari, Saeid; Goh, Yong M; Rajion, Mohamed A; Jahromi, Mohammad F; Ahmad, Yusof H; Ebrahimi, Mahdi

    2017-02-01

    Papaya leaf methanolic extract (PLE) at concentrations of 0 (CON), 5 (LLE), 10 (MLE) and 15 (HLE) mg/250 mg dry matter (DM) with 30 mL buffered rumen fluid were incubated for 24 h to identify its effect on in vitro ruminal methanogenesis and ruminal biohydrogenation (BH). Total gas production was not affected (P > 0.05) by addition of PLE compared to the CON at 24 h of incubation. Methane (CH 4 ) production (mL/250 mg DM) decreased (P < 0.05) with increasing levels of PLE. Acetate to propionate ratio was lower (P <0.05) in MLE (2.02) and HLE (1.93) compared to the CON (2.28). Supplementation of the diet with PLE significantly (P <0.05) decreased the rate of BH of C18:1n-9 (oleic acid; OA), C18:2n-6 (linoleic acid; LA), C18:3n-3 (linolenic acid; LNA) and C18 polyunsaturated fatty acids (PUFA) compared to CON after 24 h incubation, which resulted in higher concentrations of BH intermediates such as C18:1 t11 (vaccenic acid; VA), c9t11 conjugated LA (CLA) (rumenic acid; RA) and t10c12 CLA. Real-time PCR analysis indicated that the total bacteria, total protozoa, Butyrivibrio fibrisolvens and methanogen population in HLE decreased (P <0.05) compared to CON, but the total bacteria and B. fibrisolvens population were higher (P < 0.05) in CON compared to the PLE treatment groups. © 2016 Japanese Society of Animal Science.

  1. Modulation of murine intestinal immunity by Moringa oleifera extract in experimental hymenolepiasis nana.

    Science.gov (United States)

    Abdel-Latif, M; El-Shahawi, G; Aboelhadid, S M; Abdel-Tawab, H

    2017-04-06

    The potential therapeutic value of Moringa oleifera extract (MOE), due to its anti-inflammatory and anti-oxidant effects, has been reported previously. In this study, Hymenolepis nana antigen (HNA) in combination with MOE was used in immunization against H. nana infection. Adult worm and egg counts were taken, while histological changes in the intestine were observed. Mucosal mast (MMCs) and goblet cells (GCs) were stained with specific stains, while serum and intestinal IgA were assayed using enzyme-linked immunosorbent assay (ELISA). Reduced glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS) were assayed. Real-time polymerase chain reaction (PCR) was used for detection of mRNA expression in ileum tissue. The results demonstrated an improvement in the architecture of intestinal villi, decreased inducible nitric oxide synthase (iNOs) and TBARS, and increased GSH in HNA, MOE and MOE + HNA groups. In the same groups, an increase in GCs, mucin 2 (MUC2), interleukins (IL)-4, -5 and -9, and stem cell factor (SCF) versus a decrease in both interferon-gamma (IFN-γ) and transforming growth factor (TGF-β) expression appeared. HNA and MOE + HNA increased serum and intestinal IgA, respectively. MOE decreased MMCs and achieved the highest reductions in both adult worms and eggs. In conclusion, MOE could achieve protection against H. nana infections through decreased TGF-β, IFN-γ and MMC counts versus increased GC counts, T-helper cell type 2 (Th2) cytokines and IgA level.

  2. GROWTH MODULATING PROPERTIES OF POLYPHENOLIC APPLE POMACE EXTRACT ON FOOD ASSOCIATED MICROORGANISMS

    Directory of Open Access Journals (Sweden)

    Christopher Beermann

    2013-10-01

    Full Text Available Bacteriostatic effects of plant derived polyphenols are generally proposed for food protection against microbial spoiling. This study aimed at characterizing distinct growth modification and cell-lytic properties of an apple pomace extract (APE containing short-chain and long-chain PP on food spoiling and fermenting starter bacteria. APE contained 6.76 wt % PP, 0.46 wt % glucose, 1.69 wt % fructose, 1.26 wt % starch, 3.8 wt % sorbitol, and 0.64 wt % nitrogen with a pH-value of 4.1. APE caused growth modification of prominent bacterial food spoilers, yeasts, moulds and food fermenting starter bacteria was analyzed turbidometry (180° light absorption measurement at 600 nm wavelength. Cell-lytic activity of APE was measured by a SYTOX® Green fluorescence cell viability assay. APE 1.5 w/w % reduced the growth of gram-positive and gram-negative food spoiling bacteria in dose-dependent manner up to 35.00%. Bacillus subtilis growth was reduced up to 10.53% comparable to 1.01 µg/ mL ampicillin or 0.144 mg/ mL sulfamethoxazol. In contrast, the growth of several fermenting starter bacteria increased at 1.5 w/w % APE up to 167.65% whereas expansion of yeasts and moulds were unaffected. Neither specific cell-lytic activities of APE could be examined on gram-positive and gram-negative food spoiler nor food fermenting starter bacteria. This study indicates that APE is a bacteriostatic but not a cell-lytic agent against food spoiling bacteria. Instead, the growth of specific lactic acid bacteria was supported by APE. Therefore, APE might stabilize explicit food fermentation processes.

  3. Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2016-06-01

    Full Text Available We previously demonstrated that the organic extract of Spirulina platensis (SPE, an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β, but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.

  4. Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia-reperfusion injury.

    Science.gov (United States)

    Pan, Tai-Long; Wu, Tung-Ho; Wang, Pei-Wen; Leu, Yann-Lii; Sintupisut, Nardnisa; Huang, Chun-Hsun; Chang, Fang-Rong; Wu, Yang-Chang

    2013-08-01

    Hepatic ischemia-reperfusion (IR) injury is a common clinical problem and ROS may be a contributing factor on IR injury. The current study evaluates the potential protective effect of saffron ethanol extract (SEE) in a rat model upon hepatic IR injury. Caspases 3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) results showed increased cell death in the IR samples; reversely, minor apoptosis was detected in the SEE/IR group. Pretreatment with SEE significantly restored the content of antioxidant enzymes (SOD1 and catalase) and remarkably inhibited the intracellular ROS concentration in terms of reducing p47phox translocation. Proteome tools revealed that 20 proteins were significantly modulated in protein intensity between IR and SEE/IR groups. Particularly, SEE administration could attenuate the carbonylation level of several chaperone proteins. Network analysis suggested that saffron extract could alleviate IR-induced ER stress and protein ubiquitination, which finally lead to cell apoptosis. Taken together, SEE could reduce hepatic IR injury through modulating protein oxidation and our results might help to develop novel therapeutic strategies against ROS-caused diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Chemically functionalized single-walled carbon nanotube films modulate the morpho-functional and proliferative characteristics of astrocytes.

    Science.gov (United States)

    Gottipati, Manoj K; Samuelson, Josheua J; Kalinina, Irina; Bekyarova, Elena; Haddon, Robert C; Parpura, Vladimir

    2013-09-11

    We used single-walled carbon nanotube (CNT) films to modulate the morpho-functional and proliferative characteristics of astrocytes. When plated on the CNT films of various thicknesses, astrocytes grow bigger and rounder in shape with a decrease in the immunoreactivity of glial fibrillary acidic protein along with an increase in their proliferation, changes associated with the dedifferentiation of astrocytes in culture. Thus, CNT films, as a coating material for electrodes used in brain machine interface, could reduce astrogliosis around the site of implantation.

  6. Development of a Kelp-type Structure Module in a Coastal Ocean Model to Assess the Hydrodynamic Impact of Seawater Uranium Extraction Technology

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Taiping; Khangaonkar, Tarang; Long, Wen; Gill, Gary A.

    2014-02-07

    In recent years, with the rapid growth of global energy demand, the interest in extracting uranium from seawater for nuclear energy has been renewed. While extracting seawater uranium is not yet commercially viable, it serves as a “backstop” to the conventional uranium resources and provides an essentially unlimited supply of uranium resource. With recent advances in seawater uranium extraction technology, extracting uranium from seawater could be economically feasible when the extraction devices are deployed at a large scale (e.g., several hundred km2). There is concern however that the large scale deployment of adsorbent farms could result in potential impacts to the hydrodynamic flow field in an oceanic setting. In this study, a kelp-type structure module was incorporated into a coastal ocean model to simulate the blockage effect of uranium extraction devices on the flow field. The module was quantitatively validated against laboratory flume experiments for both velocity and turbulence profiles. The model-data comparison showed an overall good agreement and validated the approach of applying the model to assess the potential hydrodynamic impact of uranium extraction devices or other underwater structures in coastal oceans.

  7. Coffea arabica Seed Extract Stimulate the Cellular Immune Function and Cyclophosphamide-induced Immunosuppression in Mice

    Science.gov (United States)

    Rafiul Haque, Mohammad; Ansari, Shahid Hussain; Rashikh, Azhar

    2013-01-01

    In this study, we investigate the immunostimulatory effects of alcoholic extract of the coffee seed on cell-mediated immune response and cyclophosphamide-induced (CP) immunosuppressed mice. The assessment of cellular immune function was carried out by the measurement of delayed-type hypersensitivity (DTH) response. According to the literature survey, cyclophosphamide has only suppressing effect on the lymphoid organ, white blood cell (WBC) and other parts of humoral immunity. Humoral immunity was assessed by the hemagglutination antibody titre. Mice were treated with three doses of extract (50, 150 and 250 mg/Kg body weight per os). Relative organ weight and WBC counts were also studied in these animals. At doses of 50 and 150, a significant increase (p < 0.05) in relative organ weight of spleen and thymus was observed but there was no effect on kidney and liver weights. WBC counts was also increased significantly (p < 0.001) in all doses of the plant extract. Coffea arabica extract elicited a significant (p < 0.001) increase in the DTH response at doses of 50 and 150 mg/Kg, but the change at higher dose of 250 mg/Kg was not statistically significant. In the HT test, plant extract also showed modulatory effect at all doses groups. Over all, coffee seed showed the stimulatory effect on cellular immune function and cyclophosphamide induced immunosuppression in mice. PMID:24250577

  8. Green Extraction from Pomegranate Marcs for the Production of Functional Foods and Cosmetics.

    Science.gov (United States)

    Boggia, Raffaella; Turrini, Federica; Villa, Carla; Lacapra, Chiara; Zunin, Paola; Parodi, Brunella

    2016-10-18

    The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still edible, they are usually discharged during juice production and, thus, they represent a great challenge in an eco-sustainable industrial context. Green technologies, such as ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), have been employed to convert these organic residues into recycled products with high added value. UAE and MAE were used both in parallel and in series in order to make a comparison and to ensure exhaustive extractions, respectively. Water, as an environmentally friendly extraction solvent, has been employed. The results were compared with those ones coming from a conventional extraction. The most promising extract, in terms of total polyphenol yield and radical scavenging activity, has been tested both as a potential natural additive and as a functional ingredient after its incorporation in a real food model and in a real cosmetic matrix, respectively. This study represents a proposal to the agro-alimentary sector given the general need of environmental "responsible care".

  9. Green Extraction from Pomegranate Marcs for the Production of Functional Foods and Cosmetics

    Directory of Open Access Journals (Sweden)

    Raffaella Boggia

    2016-10-01

    Full Text Available The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp and aril residues. Even if they are still edible, they are usually discharged during juice production and, thus, they represent a great challenge in an eco-sustainable industrial context. Green technologies, such as ultrasound assisted extraction (UAE and microwave assisted extraction (MAE, have been employed to convert these organic residues into recycled products with high added value. UAE and MAE were used both in parallel and in series in order to make a comparison and to ensure exhaustive extractions, respectively. Water, as an environmentally friendly extraction solvent, has been employed. The results were compared with those ones coming from a conventional extraction. The most promising extract, in terms of total polyphenol yield and radical scavenging activity, has been tested both as a potential natural additive and as a functional ingredient after its incorporation in a real food model and in a real cosmetic matrix, respectively. This study represents a proposal to the agro-alimentary sector given the general need of environmental “responsible care”.

  10. Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation

    Science.gov (United States)

    Holst, Sebastian C.; Müller, Thomas; Valomon, Amandine; Seebauer, Britta; Berger, Wolfgang; Landolt, Hans-Peter

    2017-01-01

    Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans. PMID:28393838

  11. Electrical synapses between AII amacrine cells in the retina: Function and modulation.

    Science.gov (United States)

    Hartveit, Espen; Veruki, Margaret Lin

    2012-12-03

    Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on the recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca(2+) dynamics. This article is part of a Special Issue entitled Electrical Synapses. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Modulation of p-glycoprotein transport function at the blood-brain barrier.

    Science.gov (United States)

    Bauer, Björn; Hartz, Anika M S; Fricker, Gert; Miller, David S

    2005-02-01

    The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which p-glycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of p-glycoprotein substrates.

  13. Feeding of the water extract from Ganoderma lingzhi to rats modulates secondary bile acids, intestinal microflora, mucins, and propionate important to colon cancer.

    Science.gov (United States)

    Yang, Yongshou; Nirmagustina, Dwi Eva; Kumrungsee, Thanutchaporn; Okazaki, Yukako; Tomotake, Hiroyuki; Kato, Norihisa

    2017-09-01

    Consumption of reishi mushroom has been reported to prevent colon carcinogenesis in rodents, although the underlying mechanisms remain unclear. To investigate this effect, rats were fed a high-fat diet supplemented with 5% water extract from either the reishi mushroom (Ganoderma lingzhi) (WGL) or the auto-digested reishi G. lingzhi (AWGL) for three weeks. Both extracts markedly reduced fecal secondary bile acids, such as lithocholic acid and deoxycholic acid (colon carcinogens). These extracts reduced the numbers of Clostridium coccoides and Clostridium leptum (secondary bile acids-producing bacteria) in a per g of cecal digesta. Fecal mucins and cecal propionate were significantly elevated by both extracts, and fecal IgA was significantly elevated by WGL, but not by AWGL. These results suggest that the reishi extracts have an impact on colon luminal health by modulating secondary bile acids, microflora, mucins, and propionate that related to colon cancer.

  14. Aptamer-functionalized Fe3 O4 magnetic nanoparticles as a solid-phase extraction adsorbent for the selective extraction of berberine from Cortex phellodendri.

    Science.gov (United States)

    Jiang, Ling-Feng; Chen, Bo-Cheng; Chen, Ben; Li, Xue-Jian; Liao, Hai-Lin; Zhang, Wen-Yan; Wu, Lin

    2017-07-01

    The extraction adsorbent was fabricated by immobilizing the highly specific recognition and binding of aptamer onto the surface of Fe3 O4 magnetic nanoparticles, which not only acted as recognition elements to recognize and capture the target molecule berberine from the extract of Cortex phellodendri, but also could favor the rapid separation and purification of the bound berberine by using an external magnet. The developed solid-phase extraction method in this work was useful for the selective extraction and determination of berberine in Cortex phellodendri extracts. Various conditions such as the amount of aptamer-functionalized Fe3 O4 magnetic nanoparticles, extraction time, temperature, pH value, Mg2+ concentration, elution time and solvent were optimized for the solid-phase extraction of berberine. Under optimal conditions, the purity of berberine extracted from Cortex phellodendri was as high as 98.7% compared with that of 4.85% in the extract, indicating that aptamer-functionalized Fe3 O4 magnetic nanoparticles-based solid-phase extraction method was very effective for berberine enrichment and separation from a complex herb extract. The applicability and reliability of the developed solid-phase extraction method were demonstrated by separating berberine from nine different concentrations of one Cortex phellodendri extract. The relative recoveries of the spiked solutions of all the samples were between 95.4 and 111.3%, with relative standard deviations ranging between 0.57 and 1.85%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Modulation of the multidrug efflux pump EmrD-3 from Vibrio cholerae by Allium sativum extract and the bioactive agent allyl sulfide plus synergistic enhancement of antimicrobial susceptibility by A. sativum extract.

    Science.gov (United States)

    Bruns, Merissa M; Kakarla, Prathusha; Floyd, Jared T; Mukherjee, Mun Mun; Ponce, Robert C; Garcia, John A; Ranaweera, Indrika; Sanford, Leslie M; Hernandez, Alberto J; Willmon, T Mark; Tolson, Grace L; Varela, Manuel F

    2017-04-21

    The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.

  16. Using sub-resolution features for self-compensation of the modulation transfer function in remote sensing.

    Science.gov (United States)

    Li, Jin; Liu, Zilong; Liu, Fengdeng

    2017-02-20

    Space smart optical orbiting payloads integrated with attitude and position (SSPIAP) are emerging as an essential tool that is extensively used in microsatellites. The on-orbit imaging link of SSPIAPs includes atmospheric disturbances, defocusing, and relative motion, and other noises, thereby resulting in low modulation transfer function (MTF) and poor image quality. The introduction of MTF compensations has pushed the limits of optical imaging, enabling high-resolution on-orbit dynamic imaging. However, the external targets for compensating MTF are limited by space and time because the availability and access to external targets are infrequently easy when a remote sensor is working on-orbit. Here, a new and robust MTF self-compensation method for a SSPIAP is proposed. In comparison with conventional methods with external targets, this method utilizes multiple natural sub-resolution features (SRFs), occupying several pixels on a uniform background, as observation targets which makes MTFC more maneuverable, robust and authentic. A mathematical morphology algorithm is used to extract SRFs. Moreover, the method relies on a regularization total variation energy function, a sparse prior framework, to invert the MTF. Experimental measurements confirm that the proposed method is effective and convenient to implement. This technique does not rely on specific external targets to compensate the MTF, making it potentially suitable for on-orbit dynamic long-range imaging.

  17. A NEW METHOD FOR EXTRACTING SPIN-DEPENDENT NEUTRON STRUCTURE FUNCTIONS FROM NUCLEAR DATA

    Energy Technology Data Exchange (ETDEWEB)

    Kahn, Y.F.; Melnitchouk, W.

    2009-01-01

    High-energy electrons are currently the best probes of the internal structure of nucleons (protons and neutrons). By collecting data on electrons scattering off light nuclei, such as deuterium and helium, one can extract structure functions (SFs), which encode information about the quarks that make up the nucleon. Spin-dependent SFs, which depend on the relative polarization of the electron beam and the target nucleus, encode quark spins. Proton SFs can be measured directly from electron-proton scattering, but those of the neutron must be extracted from proton data and deuterium or helium-3 data because free neutron targets do not exist. At present, there is no reliable method for accurately determining spin-dependent neutron SFs in the low-momentum-transfer regime, where nucleon resonances are prominent and the functions are not smooth. The focus of this study was to develop a new method for extracting spin-dependent neutron SFs from nuclear data. An approximate convolution formula for nuclear SFs reduces the problem to an integral equation, for which a recursive solution method was designed. The method was then applied to recent data from proton and deuterium scattering experiments to perform a preliminary extraction of spin-dependent neutron SFs in the resonance region. The extraction method was found to reliably converge for arbitrary test functions, and the validity of the extraction from data was verifi ed using a Bjorken integral, which relates integrals of SFs to a known quantity. This new information on neutron structure could be used to assess quark-hadron duality for the neutron, which requires detailed knowledge of SFs in all kinematic regimes.

  18. Lipoproteins as modulators of atherothrombosis: From endothelial function to primary and secondary coagulation.

    Science.gov (United States)

    Ouweneel, Amber B; Van Eck, Miranda

    2016-07-01

    Atherothrombosis is a complication of atherosclerosis that causes acute cardiovascular events such as myocardial infarction and stroke. Circulating lipid levels are highly correlated with atherosclerotic plaque development. In addition, experimental evidence suggests that lipids also directly influence thrombosis and influence the risk and the outcome of acute cardiovascular events. Plasma lipoproteins influence three aspects important to atherothrombosis: endothelial function, platelet aggregation (primary coagulation) and secondary coagulation. Overall, VLDL, LDL and oxLDL promote thrombus formation, whereas HDL shows antithrombotic actions. In this review we will address the current knowledge about modulation of atherothrombosis by lipoproteins, summarizing findings from in vitro and in vivo animal studies, as well as from observational and interventional studies in humans. We will conclude with future perspectives for lipid modulation in the prevention of atherothrombosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Effects of Pomegranate Extract Supplementation on Cardiovascular Risk Factors and Physical Function in Hemodialysis Patients.

    Science.gov (United States)

    Wu, Pei-Tzu; Fitschen, Peter J; Kistler, Brandon M; Jeong, Jin Hee; Chung, Hae Ryong; Aviram, Michael; Phillips, Shane A; Fernhall, Bo; Wilund, Kenneth R

    2015-09-01

    The purpose of this study was to evaluate the effects of oral supplementation with pomegranate extract on cardiovascular risk, physical function, oxidative stress, and inflammation in hemodialysis (HD) patients. Thirty-three HD subjects were randomized to the pomegranate (POM) or placebo (CON) group. Patients in POM ingested a 1000 mg capsule of a purified pomegranate polyphenol extract 7 days/week for 6 months. Individuals in CON ingested a noncaloric placebo capsule using the same protocol. Measurements were conducted at baseline and repeated 6 months following the start of the intervention. Brachial blood pressure (BP) was obtained using an automatic digital BP monitor. Cardiovascular risk was assessed using ultrasound and arterial tonometry. Blood samples were collected for the measurements of circulating markers of inflammation, oxidative stress, and antioxidant capacity. Muscle strength and physical function were assessed by isokinetic dynamometry, a validated shuttle walk test, and a battery of tests to assess functional fitness. Systolic blood pressure and diastolic blood pressure were reduced by 24 ± 13.7 and 10 ± 5.3 mmHg, respectively, in POM (P pomegranate supplementation had no effect on other markers of cardiovascular disease risk, inflammation and oxidative stress, or measures of physical function and muscle strength. While pomegranate extract supplementation may reduce BP and increase the antioxidant activity in HD patients, it does not improve other markers of cardiovascular risk, physical function, or muscle strength.

  20. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

    Directory of Open Access Journals (Sweden)

    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  1. A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Minakshi Rana

    2016-07-01

    Full Text Available The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L. enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa extract (CMCE. CMCE (1 or 10 µg/mL; 14 h significantly decreased LPS (50-100 ng/mL induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100 and 300 mg/kg; 10 days p.o. pre-treated and LPS (10 mg/kg challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1β, nitrite, aortic iNOS expression and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3 and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia.

  2. Chemical Composition and Some Functional Properties of Beef Lung Protein Concentrate Extracted by Alkaline Method

    Directory of Open Access Journals (Sweden)

    Khotibul Umam Al Awwaly

    2017-03-01

    Full Text Available This research was carried out to examine the functional properties of beef lung protein concentrates. The extraction was performed as a function of pH and time. The pI method was applied in the precipitation of proteins from beef lung. Beef lung protein concentrates contained 85.13% protein. The functional properties of the protein concentrates were compared to those of some commercial ingredients as whey protein concentrates, and casein. Protein from beef lung exhibited better foaming property than casein and better emulsifying property than whey protein. The use of beef lung proteins appears to be an interesting opportunity to obtain added value slaughterhouse by-products.

  3. Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

    Science.gov (United States)

    Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

    2016-07-01

    The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

  4. Peroxisome proliferator-activated receptor α ligands and modulators from dietary compounds: Types, screening methods and functions.

    Science.gov (United States)

    Yang, Haixia; Xiao, Lei; Wang, Nanping

    2017-04-01

    Peroxisome proliferator-activated receptor α (PPARα) plays a key role in lipid metabolism and glucose homeostasis and a crucial role in the prevention and treatment of metabolic diseases. Natural dietary compounds, including nutrients and phytochemicals, are PPARα ligands or modulators. High-throughput screening assays have been developed to screen for PPARα ligands and modulators in our diet. In the present review, we discuss recent advances in our knowledge of PPARα, including its structure, function, and ligand and modulator screening assays, and summarize the different types of dietary PPARα ligands and modulators. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  5. A mammalian nervous system-specific plasma membrane proteasome complex that modulates neuronal function

    Science.gov (United States)

    Ramachandran, Kapil V.; Margolis, Seth S.

    2017-01-01

    In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It remains unclear how proteasomes can acutely regulate such processes, as this is inconsistent with their canonical role in proteostasis. Here, we made the discovery of a mammalian nervous system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is tightly associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of this membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked extracellular peptide production and attenuated neuronal activity-induced calcium signaling. Moreover, membrane proteasome-derived peptides are sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes primarily function to maintain proteostasis, and highlight a form of neuronal communication through a membrane proteasome complex. PMID:28287632

  6. Functional brain asymmetry, attentional modulation, and interhemispheric transfer in boys with Tourette syndrome

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Lundervold, Arvid; Grüner, Renate

    2007-01-01

    on the right ear stimulus in the dichotic listening situation is thought to involve the same prefrontal attentional and executive functions that are involved in the suppression of tics, whereas, performance when focusing attention on the left ear stimulus additionally involves a callosal transfer...... of information. In light of presumed disturbances in transfer of information across the corpus callosum, we hypothesized that children with TS would, however, have difficulty modulating the functional lateralization that ensues through a shift of attention to the left side. This hypothesis was tested...... by exploring the correlations between CC size and left ear score in the forced-left condition. Twenty boys with TS were compared with 20 age- and handedness-matched healthy boys. Results indicated similar performance in the TS and HC groups for lateralization of hemispheric function. TS subjects were also able...

  7. Age-related decline in brain resources modulates genetic effects on cognitive functioning

    Directory of Open Access Journals (Sweden)

    Ulman Lindenberger

    2008-12-01

    Full Text Available Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging.Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008, who reported that the effects of the Catechol-O-Methyltransferase (COMT gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed.

  8. Morinda citrifolia L. fruit extracts modulates H2O2-induced oxidative stress in human liposarcoma SW872 cells.

    Science.gov (United States)

    Ruhomally, Z; Somanah, J; Bahorun, T; Neergheen-Bhujun, V S

    2016-07-01

    Morinda citrifolia L. commonly known as noni is used by the pharmaceutical and cosmetic industries due to the plethora of pharmacological activities of its metabolites. In Mauritius, the fruits of M. citrifolia are used in folk medicine against a number of indications. The present study aimed at evaluating the antioxidant activity of ripe and unripe noni fruit at both biochemical and cellular levels. Using an array of established assay systems, the fruit antioxidant propensity was assessed in terms of its radical scavenging, iron reducing and metal chelating potentials. Ascorbic acid, total phenolic and total flavonoid contents of the fruits were also determined. The ascorbic acid content of ripe noni was 76.24 ± 1.13 mg/100 g while total phenolics of ripe and unripe fruit extracts were 748.40 ± 8.85 μg and 770.34 ± 2.27 μg GAE g(-1) FW respectively. Both the ripe and unripe extracts of M. citrifolia were potent scavengers of nitric oxide, superoxide and hydroxyl radicals. The ferric reducing capacity ranged from 11.26 ± 0.33 to 11.90 ± 0.20 mM Fe(2+) g(-1) FW while the IC50 values for the iron (II) chelating power were 0.50 ± 0.01 and 1.74 ± 0.01 g FW/mL for the ripe and unripe fruit extracts respectively. Cellular studies additionally demonstrated that noni were able to dose-dependently counteract accumulation of reactive oxygen species (ROS)-induced oxidative stress, a potential obesogenic factor within human liposarcoma SW872 cells as well as significantly restore cell death within the concentration range of 0.106-0.813 g/mL. Results reported herein suggest noni as an interesting source of prophylactic antioxidants modulated by its polyphenol composition.

  9. Catechol-O-Methyltransferase Val158Met Polymorphism Modulates Gray Matter Volume and Functional Connectivity of the Default Mode Network

    Science.gov (United States)

    Tian, Tian; Qin, Wen; Liu, Bing; Wang, Dawei; Wang, Junping; Jiang, Tianzi; Yu, Chunshui

    2013-01-01

    The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype × gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial superior frontal gyrus (mSFG) was found only in male Val/Val subjects. The rsFC analysis revealed that both the PCC and mSFG were functionally correlated with brain regions of the default mode network (DMN). Both of these regions showed decreased rsFCs with different parts of the frontopolar cortex of the DMN in Val/Val individuals than Met carriers. Our findings suggest that the COMT Val158Met polymorphism modulates both the structure and functional connectivity within the DMN and that gender interactions should be considered in studies of the effect of this genetic variant, especially those involving prefrontal morphology. PMID:24147141

  10. Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats

    Directory of Open Access Journals (Sweden)

    Haw-Wen Chen

    2013-01-01

    Full Text Available Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0–12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.

  11. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    Science.gov (United States)

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-03-01

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  12. Calibration of Modulation Transfer Function of Surface Profilometers with 1D and 2D Binary Pseudo-random Array Standards

    Energy Technology Data Exchange (ETDEWEB)

    Yashchuk, Valeriy V.; McKinney, Wayne R.; Takacs, Peter Z.

    2008-05-19

    We suggest and describe the use of a binary pseudo-random grating as a standard test surface for calibration of the modulation transfer function of microscopes. Results from calibration of a MicromapTM-570 interferometric microscope are presented.

  13. Modulation of immune function by a modified bovine whey protein concentrate.

    Science.gov (United States)

    Cross, M L; Gill, H S

    1999-08-01

    The commercial preparation of dairy foodstuffs generates large volumes of by-products, many of which have as yet undocumented effects on mammalian immune function. In the present report, a modified whey protein concentrate (mWPC), derived as a by-product from the commercial manufacture of cheese, was tested for its ability to modulate murine immune function in vitro. The mWPC suppressed T and B lymphocyte proliferative responses to mitogens in a dose-dependent fashion. The mWPC also suppressed alloantigen-induced lymphocyte proliferation during a mixed leucocyte reaction, but showed no suppressive effect against IL-2-sustained proliferation of mitogen-activated T cell blasts. Other indices of lymphocyte activation, such as cytokine secretion and the formation of activated (CD25+) T cell blasts, were suppressed by the mWPC, suggesting that the mode of suppression may be to inhibit the lymphocyte activation process. Enzymatic digestion by pepsin and pancreatin, under physiologically realistic conditions in vitro, ablated the immunomodulatory function of the mWPC. These results are discussed in relation to the potential development of complex-mixture dairy products into health-modulating products.

  14. Continuous Descending Modulation of the Spinal Cord Revealed by Functional MRI.

    Directory of Open Access Journals (Sweden)

    Patrick W Stroman

    Full Text Available Spontaneous variations in spinal cord activity may arise from regulation of any of a number of functions including sensory, motor, and autonomic control. Here, we use functional MRI (fMRI of healthy participants to identify properties of blood oxygenation-level dependent (BOLD variations in the spinal cord in response to knowledge that either a noxious stimulus is impending, or that no stimulus is to be expected. Expectation of a noxious stimulus, or no stimulus, is shown to have a significant effect on wide-spread BOLD signal variations in the spinal cord over the entire time period of the fMRI acquisition. Coordination of BOLD responses between/within spinal cord and brainstem regions are also influenced by this knowledge. We provide evidence that such signal variations are the result of continuous descending modulation of spinal cord function. BOLD signal variations in response to noxious stimulation of the hand are also shown, as in previous studies. The observation of both continuous and reactive BOLD responses to emotional/cognitive factors and noxious peripheral stimulation may have important implications, not only for our understanding of endogenous pain modulation, but also in showing that spinal cord activity is under continuous regulatory control.

  15. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function.

    Science.gov (United States)

    Ottman, Noora; Reunanen, Justus; Meijerink, Marjolein; Pietilä, Taija E; Kainulainen, Veera; Klievink, Judith; Huuskonen, Laura; Aalvink, Steven; Skurnik, Mikael; Boeren, Sjef; Satokari, Reetta; Mercenier, Annick; Palva, Airi; Smidt, Hauke; de Vos, Willem M; Belzer, Clara

    2017-01-01

    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function.

  16. Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

    Science.gov (United States)

    Curado, Marco; Fritsch, Brita; Reis, Janine

    2016-02-04

    Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

  17. Determination of Lateral Modulation Apodization Functions Using a Regularized, Weighted Least Squares Estimation

    Directory of Open Access Journals (Sweden)

    Chikayoshi Sumi

    2010-01-01

    Full Text Available Recently, work in this group has focused on the lateral cosine modulation method (LCM which can be used for next-generation ultrasound (US echo imaging and tissue displacement vector/strain tensor measurements (blood, soft tissues, etc.. For instance, in US echo imaging, a high lateral spatial resolution as well as a high axial spatial resolution can be obtained, and in tissue displacement vector measurements, accurate measurements of lateral tissue displacements as well as of axial tissue displacements can be realized. For an optimal determination of an apodization function for the LCM method, the regularized, weighted minimum-norm least squares (WMNLSs estimation method is presented in this study. For designed Gaussian-type point spread functions (PSFs with lateral modulation as an example, the regularized WMNLS estimation in simulations yields better approximations of the designed PSFs having wider lateral bandwidths than a Fraunhofer approximation and a singular-value decomposition (SVD. The usefulness of the regularized WMNLS estimation for the determination of apodization functions is demonstrated.

  18. Effects of Aqueous Stem Extract of Massularia Acuminata on Some Liver Function Indices of Male Rats

    Directory of Open Access Journals (Sweden)

    Musa Toyin Yakubu

    2012-09-01

    Full Text Available Background: Massularia acuminata has been claimed to be used in managingseveral ailments in folk medicine and in some instances substantiated withscientific data. This however has been without recourse to its safety. Therefore,aqueous stem extract of M. acuminata was evaluated for its effects on somefunction indices of the liver of male rats.Methods: Sixty, male rats were grouped into 4 (A, B, C and D such that Group A(control was orally administered 1cm3 of distilled water while those in groups B, Cand D received orally 1 cm3 of extract corresponding to 250, 500 and 1000 mg/kgbody weight respectively. Some biochemical parameters of liver function wereevaluated in the animals after 1, 7 and 21 daily doses.Results: The extract significantly decreased (P<0.05 the activity of alkalinephosphatase in the liver of rats throughout the experimental period. This decreasewas accompanied by corresponding increase in the serum enzyme. In contrast, allthe doses of the extract increased the activities of both the AST and ALT in the liverand serum aspartate aminotransferase and alanine aminotransferase as well asthe concentrations of serum total bilirubin, protein and albumin.Conclusion: This study has revealed that the aqueous stem extract of Massulariaacuminata at the doses of 250-1000 mg/kg body weight hampered the normalfunctioning of the liver of male rats and is therefore not safe for oral consumption atthe doses investigated.

  19. Direct effects of Vaccinium myrtillus L. fruit extracts on rat heart mitochondrial functions.

    Science.gov (United States)

    Trumbeckaitė, S; Burdulis, D; Raudonė, L; Liobikas, J; Toleikis, A; Janulis, V

    2013-04-01

    In this study, the direct influence of bilberry (Vaccinium myrtillus) fruit extracts (aqueous and ethanolic) rich in anthocyanins on the oxidative phosphorylation of isolated rat heart mitochondria was investigated in vitro. Higher concentrations of bilberry extracts concentration-dependently inhibited mitochondrial state 3 respiration (by 23%-61%) with pyruvate plus malate, mildly (by 1.2- to 1.3-fold) uncoupled the oxidative phosphorylation, and increased (by 30%-87%) the state 4 respiration rate in the presence of exogenous cytochrome c. Succinate oxidation was less affected. Pure anthocyanins, the main components of used extracts, malvidin-3-glucoside, malvidin-3-galactoside, and cyanidin-3-galactoside, had no effect on oxidation of pyruvate plus malate. A statistically significant decrease in H2 O2 production by mitochondria was found in the presence of bilberry fruit extracts. Our findings show that bilberry fruit anthocyanin-rich extracts possess direct effects on rat heart mitochondrial function in vitro. These findings give the first insights into the mechanism(s) of their action on cellular energy metabolism. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Modulating Function-Based Method for Parameter and Source Estimation of Partial Differential Equations

    KAUST Repository

    Asiri, Sharefa M.

    2017-10-08

    Partial Differential Equations (PDEs) are commonly used to model complex systems that arise for example in biology, engineering, chemistry, and elsewhere. The parameters (or coefficients) and the source of PDE models are often unknown and are estimated from available measurements. Despite its importance, solving the estimation problem is mathematically and numerically challenging and especially when the measurements are corrupted by noise, which is often the case. Various methods have been proposed to solve estimation problems in PDEs which can be classified into optimization methods and recursive methods. The optimization methods are usually heavy computationally, especially when the number of unknowns is large. In addition, they are sensitive to the initial guess and stop condition, and they suffer from the lack of robustness to noise. Recursive methods, such as observer-based approaches, are limited by their dependence on some structural properties such as observability and identifiability which might be lost when approximating the PDE numerically. Moreover, most of these methods provide asymptotic estimates which might not be useful for control applications for example. An alternative non-asymptotic approach with less computational burden has been proposed in engineering fields based on the so-called modulating functions. In this dissertation, we propose to mathematically and numerically analyze the modulating functions based approaches. We also propose to extend these approaches to different situations. The contributions of this thesis are as follows. (i) Provide a mathematical analysis of the modulating function-based method (MFBM) which includes: its well-posedness, statistical properties, and estimation errors. (ii) Provide a numerical analysis of the MFBM through some estimation problems, and study the sensitivity of the method to the modulating functions\\' parameters. (iii) Propose an effective algorithm for selecting the method\\'s design parameters

  1. Security camera resolution measurements: Horizontal TV lines versus modulation transfer function measurements.

    Energy Technology Data Exchange (ETDEWEB)

    Birch, Gabriel Carisle [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Griffin, John Clark [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    The horizontal television lines (HTVL) metric has been the primary quantity used by division 6000 related to camera resolution for high consequence security systems. This document shows HTVL measurements are fundamen- tally insufficient as a metric to determine camera resolution, and propose a quantitative, standards based methodology by measuring the camera system modulation transfer function (MTF), the most common and accepted metric of res- olution in the optical science community. Because HTVL calculations are easily misinterpreted or poorly defined, we present several scenarios in which HTVL is frequently reported, and discuss their problems. The MTF metric is discussed, and scenarios are presented with calculations showing the application of such a metric.

  2. Modulation Transfer Function of a Gaussian Beam Based on the Generalized Modified Atmospheric Spectrum

    Directory of Open Access Journals (Sweden)

    Chao Gao

    2016-01-01

    Full Text Available This paper investigates the modulation transfer function of a Gaussian beam propagating through a horizontal path in weak-fluctuation non-Kolmogorov turbulence. Mathematical expressions are obtained based on the generalized modified atmospheric spectrum, which includes the spectral power law value of non-Kolmogorov turbulence, the finite inner and outer scales of turbulence, and other optical parameters of the Gaussian beam. The numerical results indicate that the atmospheric turbulence would produce less negative effects on the wireless optical communication system with an increase in the inner scale of turbulence. Additionally, the increased outer scale of turbulence makes a Gaussian beam influenced more seriously by the atmospheric turbulence.

  3. Work function modulation and thermal stability of reduced graphene oxide gate electrodes in MOS devices.

    Science.gov (United States)

    Misra, Abhishek; Kalita, Hemen; Kottantharayil, Anil

    2014-01-22

    Work function (WF) tuning of the contact electrodes is a key requirement in several device technologies, including organic photovoltaics (OPVs), organic light-emitting diodes (OLEDs), and complementary metal oxide semiconductor (CMOS) transistors. Here, we demonstrate that the WF of the gate electrode in an MOS structure can be modulated from 4.35 eV (n-type metal) to 5.28 eV (p-type metal) by sandwiching different thicknesses of reduced graphene oxide (rGO) layers between top contact metals and gate dielectric SiO2. The WF of the gate electrode shows strong dependence on the rGO thickness and is seen to be nearly independent of the contact metals used. The observed WF modulation is attributed to the different amounts of oxygen concentrations in different thicknesses of rGO layers. Importantly, this oxygen concentration can also be varied by the reduction extent of the graphene oxide as experimentally demonstrated. The results are verified by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses. The obtained WF values are thermally stable up to 800 °C. At further high temperatures, diffusion of metal through the rGO sheets is the main cause for WF instability, as confirmed by cross-sectional high-resolution transmission electron microscopy analysis. These findings are not limited to MOS devices, and the WF modulation technique has the potential for applications in other technologies such as OLEDs and OPVs involving graphene as conducting electrodes.

  4. Elucidation of the mechanism of the regulatory function of the Ig1 module of the fibroblast growth factor receptor 1

    DEFF Research Database (Denmark)

    Kiselyov, Vladislav; Kochoyan, Artur; Poulsen, Flemming

    2006-01-01

    The extracellular part of the fibroblast growth factor (FGF) receptor (FGFR) consists of up to three Ig modules (Ig1-Ig3), in which the Ig2 and Ig3 modules determine affinity and specificity for FGF and heparin. The FGFR isoforms lacking the Ig1 module have higher affinity for FGF and heparin than...... the triple Ig-module isoforms, suggesting that the Ig1 module is involved in the regulation of the FGFR-ligand interaction. We show here by surface plasmon resonance and NMR analyses that the Ig1 module binds to the Ig2 module, and identify by NMR the binding sites involved in the Ig1-Ig2 interaction....... The identified binding site in the Ig2 module was found to be in the area of the FGF-Ig2 and Ig2-heparin contact sites, thus providing direct structural evidence that the Ig1 module functions as a competitive autoinhibitor of the FGFR-ligand interaction. Furthermore, the Ig1 binding site of the Ig2 module...

  5. Safety assessment of Syzygium aromaticum flower bud (clove) extract with respect to testicular function in mice.

    Science.gov (United States)

    Mishra, Raghav Kumar; Singh, Shio Kumar

    2008-10-01

    The flower buds of Syzygium aromaticum (clove), a common food flavor, have been used as indigenous medicine for the treatment of male sexual disorders in Asian countries. However, the possible mechanism(s) by which it acts at testicular level remain obscure. Therefore, to investigate its effect on testicular function, chronic oral exposure of hexane extract of flower buds of Syzygium aromaticum in three doses (15 mg, 30 mg, and 60 mg/kg BW) were evaluated for a single spermatogenic cycle (35 days) in Parkes (P) strain mice. The treatment did not induce systemic toxicity at the doses tested. Lower dose (15 mg) of the extract increased the activities of Delta(5) 3 beta-HSD and 17 beta-HSD, and serum level of testosterone. The higher doses (30 and 60 mg) of extract inhibited these parameters and induced non-uniform degenerative changes in the seminiferous tubules associated with decrease in daily sperm production and depletion of 1C (round and elongated spermatids) population. Taken together these results suggest biphasic action of hexane extract of Syzygium aromaticum flower bud on testicular function, thereby advocating a cautious use of the flower bud as an aphrodisiac in indigenous systems of medicine in Asian countries.

  6. Modulation of human muscle spindle discharge by arterial pulsations - functional effects and consequences

    NARCIS (Netherlands)

    Birznieks, I.; Boonstra, T.W.; Macefield, V.G.

    2012-01-01

    Arterial pulsations are known to modulate muscle spindle firing; however, the physiological significance of such synchronised modulation has not been investigated. Unitary recordings were made from 75 human muscle spindle afferents innervating the pretibial muscles. The modulation of muscle spindle

  7. Origin of heart rate variability and turbulence: an appraisal of autonomic modulation of cardiovascular function.

    Directory of Open Access Journals (Sweden)

    Federico eLombardi

    2011-12-01

    Full Text Available Assessment of autonomic modulation of sinus node by non-invasive techniques has provided relevant clinical information in patients with several cardiac and non-cardiac diseases and has facilitated the appraisal of neural regulatory mechanisms in normal and diseased subjects. The finding that even during resting conditions the heart period changes on a beat to beat basis and that after a premature ventricular beat there are small variations in RR interval whose measurements may be utilised to evaluate the autonomic modulation of sinus node, has provided unprecedented clinical and pathophysiological information. Heart rate variability (HRV and Heart Rate Turbulence (HRT have been extensively utilised in the clinical setting. To explain the negative predictive value of a reduced HRV it was determined that overall HRV was largely dependent on vagal mechanisms and that a reduction in HRV could reflect an increased sympathetic and a reduced vagal modulation of sinus node; i.e. an autonomic alteration favouring cardiac electrical instability. This initial interpretation was challenged by several findings indicating a greater complexity of the relationship between neural input and sinus node responsiveness as well as the possible interference with non-neural mechanisms.Under controlled conditions, however, the computation of low and high frequency components and of their ratio seems capable of providing adequate information on sympatho-vagal balance in normal subjects as well as in most patients with a preserved left ventricular function, thus providing a unique tool to investigate neural control mechanisms. Analysis on non-linear dynamics of HRV has also been utilised to describe the fractal like characteristic of the variability signal and proven effective to identify patients at risk for sudden cardiac death. A reduction on HRT parameters reflecting reduced baroreflex sensitivity as a likely result of a reduced vagal and of an increased sympathetic

  8. Membrane proteins bind lipids selectively to modulate their structure and function.

    Science.gov (United States)

    Laganowsky, Arthur; Reading, Eamonn; Allison, Timothy M; Ulmschneider, Martin B; Degiacomi, Matteo T; Baldwin, Andrew J; Robinson, Carol V

    2014-06-05

    Previous studies have established that the folding, structure and function of membrane proteins are influenced by their lipid environments and that lipids can bind to specific sites, for example, in potassium channels. Fundamental questions remain however regarding the extent of membrane protein selectivity towards lipids. Here we report a mass spectrometry approach designed to determine the selectivity of lipid binding to membrane protein complexes. We investigate the mechanosensitive channel of large conductance (MscL) from Mycobacterium tuberculosis and aquaporin Z (AqpZ) and the ammonia channel (AmtB) from Escherichia coli, using ion mobility mass spectrometry (IM-MS), which reports gas-phase collision cross-sections. We demonstrate that folded conformations of membrane protein complexes can exist in the gas phase. By resolving lipid-bound states, we then rank bound lipids on the basis of their ability to resist gas phase unfolding and thereby stabilize membrane protein structure. Lipids bind non-selectively and with high avidity to MscL, all imparting comparable stability; however, the highest-ranking lipid is phosphatidylinositol phosphate, in line with its proposed functional role in mechanosensation. AqpZ is also stabilized by many lipids, with cardiolipin imparting the most significant resistance to unfolding. Subsequently, through functional assays we show that cardiolipin modulates AqpZ function. Similar experiments identify AmtB as being highly selective for phosphatidylglycerol, prompting us to obtain an X-ray structure in this lipid membrane-like environment. The 2.3 Å resolution structure, when compared with others obtained without lipid bound, reveals distinct conformational changes that re-position AmtB residues to interact with the lipid bilayer. Our results demonstrate that resistance to unfolding correlates with specific lipid-binding events, enabling a distinction to be made between lipids that merely bind from those that modulate membrane

  9. Functionalization of single-walled carbon nanotubes with silver nanoparticles using Tecoma stans leaf extract

    Science.gov (United States)

    Vivekanandhan, S.; Venkateswarlu, M.; Carnahan, D.; Misra, M.; Mohanty, A. K.; Satyanarayana, N.

    2012-04-01

    Bioreduction mechanism of Tecoma stans leaf extract for the extracellular synthesis of silver nanoparticles was investigated using ultraviolet-visible spectroscopy (UV-vis). Nanostructure of the bio synthesized silver particles was confirmed by transmission electron microscopic (TEM) analysis. Crystalline cubic phase of the synthesized silver nanoparticles was confirmed by X-ray diffraction (XRD) technique. Observed rapid reduction behavior of Tecoma stans leaf extract was effectively explored for the functionalization of single-walled carbon nanotubes (SWCNT) with silver nanoparticles. Scanning electron microscopic (SEM) and TEM characterization confirmed the functionalization of single walled carbon nanotubes with the silver nanoparticles and the size of silver nanoparticles were found to be in the range of ∼5-10 nm.

  10. Effects of water extract of Curcuma longa (L.) roots on immunity and telomerase function.

    Science.gov (United States)

    Pan, Min-Hsiung; Wu, Jia-Ching; Ho, Chi-Tang; Badmaev, Vladimir

    2017-05-12

    Background Immunity and Longevity Methods A water extract of Curcuma longa (L.) [vern. Turmeric] roots (TurmericImmune™) standardized for a minimum 20 % of turmeric polysaccharides ukonan A, B, C and D was evaluated for its biological properties in in vitro tissue culture studies. Results The water extract of turmeric (TurP) exhibited induced-nitric oxide (NO) production in RAW264.7 macrophages. These results suggested the immunomodulatory effects of TurP. In addition, the polysaccharides up-regulated function of telomerase reverse transcriptase (TERT) equally to the phenolic compound from turmeric, curcumin. Conclusions The ukonan family of polysaccharides may assist in promoting cellular immune responses, tissue repair and lifespan by enhancing immune response and telomere function.

  11. Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression.

    Science.gov (United States)

    Liu, Jun; Fang, Jiliang; Wang, Zengjian; Rong, Peijing; Hong, Yang; Fan, Yangyang; Wang, Xiaoling; Park, Joel; Jin, Yu; Liu, Chunhong; Zhu, Bing; Kong, Jian

    2016-11-15

    The amygdala is a key region in emotion processing, and studies have suggested that amygdala-frontal functional connectivity deficits could be modulated by antidepressants in major depressive disorder (MDD). Transcutaneous vagus nerve stimulation (tVNS), a non-invasive, peripheral neuromodulation method at the ear, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism underlying tVNS treatment of depression has not been fully investigated. In this study, we investigated how tVNS can modulate the amygdala-lateral prefrontal network resting state functional connectivity (rsFC) in mild or moderate major depressive disorder (MDD) patients. Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments for four weeks. Resting state fMRI scans were applied before and after treatments. After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) scores were reduced significantly in the tVNS group as compared with the sham tVNS group. The rsFC in the tVNS group between the right amygdala and left dorsolateral prefrontal cortex was increased compared with sham tVNS. All the rsFC increases were also associated with HAMD reduction as well as reductions in the anxiety and retardation HAMD subscales. tVNS can significantly modulate the amygdala-lateral prefrontal rsFC of MDD patients; our results provide insights into the brain mechanism of tVNS treatment for MDD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. topPTM: a new module of dbPTM for identifying functional post-translational modifications in transmembrane proteins.

    Science.gov (United States)

    Su, Min-Gang; Huang, Kai-Yao; Lu, Cheng-Tsung; Kao, Hui-Ju; Chang, Ya-Han; Lee, Tzong-Yi

    2014-01-01

    Transmembrane (TM) proteins have crucial roles in various cellular processes. The location of post-translational modifications (PTMs) on TM proteins is associated with their functional roles in various cellular processes. Given the importance of PTMs in the functioning of TM proteins, this study developed topPTM (available online at http://topPTM.cse.yzu.edu.tw), a new dbPTM module that provides a public resource for identifying the functional PTM sites on TM proteins with structural topology. Experimentally verified TM topology data were integrated from TMPad, TOPDB, PDBTM and OPM. In addition to the PTMs obtained from dbPTM, experimentally verified PTM sites were manually extracted from research articles by text mining. In an attempt to provide a full investigation of PTM sites on TM proteins, all UniProtKB protein entries containing annotations related to membrane localization and TM topology were considered potential TM proteins. Two effective tools were then used to annotate the structural topology of the potential TM proteins. The TM topology of TM proteins is represented by graphical visualization, as well as by the PTM sites. To delineate the structural correlation between the PTM sites and TM topologies, the tertiary structure of PTM sites on TM proteins was visualized by Jmol program. Given the support of research articles by manual curation and the investigation of domain-domain interactions in Protein Data Bank, 1347 PTM substrate sites are associated with protein-protein interactions for 773 TM proteins. The database content is regularly updated on publication of new data by continuous surveys of research articles and available resources.

  13. Modulation rate transfer functions from four species of stranded odontocete (Stenella longirostris, Feresa attenuata, Globicephala melas, and Mesoplodon densirostris).

    Science.gov (United States)

    Smith, Adam B; Pacini, Aude F; Nachtigall, Paul E

    2018-01-19

    Odontocete marine mammals explore the environment by rapidly producing echolocation signals and receiving the corresponding echoes, which likewise return at very rapid rates. Thus, it is important that the auditory system has a high temporal resolution to effectively process and extract relevant information from click echoes. This study used auditory evoked potential methods to investigate auditory temporal resolution of individuals from four different odontocete species, including a spinner dolphin (Stenella longirostris), pygmy killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas), and Blainville's beaked whale (Mesoplodon densirostris). Each individual had previously stranded and was undergoing rehabilitation. Auditory Brainstem Responses (ABRs) were elicited via acoustic stimuli consisting of a train of broadband tone pulses presented at rates between 300 and 2000 Hz. Similar to other studied species, modulation rate transfer functions (MRTFs) of the studied individuals followed the shape of a low-pass filter, with the ability to process acoustic stimuli at presentation rates up to and exceeding 1250 Hz. Auditory integration times estimated from the bandwidths of the MRTFs ranged between 250 and 333 µs. The results support the hypothesis that high temporal resolution is conserved throughout the diverse range of odontocete species.

  14. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    Science.gov (United States)

    Febo, Marcelo; Ferris, Craig F

    2014-09-11

    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Modulation of function in a minimalist heme-binding membrane protein.

    Science.gov (United States)

    Shinde, Sandip; Cordova, Jeanine M; Woodrum, Brian W; Ghirlanda, Giovanna

    2012-04-01

    De novo designed heme-binding proteins have been used successfully to recapitulate features of natural hemoproteins. This approach has now been extended to membrane-soluble model proteins. Our group designed a functional hemoprotein, ME1, by engineering a bishistidine binding site into a natural membrane protein, glycophorin A (Cordova et al. in J Am Chem Soc 129:512-518, 2007). ME1 binds iron(III) protoporphyrin IX with submicromolar affinity, has a redox potential of -128 mV, and displays peroxidase activity. Here, we show the effect of aromatic residues in modulating the redox potential in the context of a membrane-soluble model system. We designed aromatic interactions with the heme through a single-point mutant, G25F, in which a phenylalanine is designed to dock against the porphyrin ring. This mutation results in roughly tenfold tighter binding to iron(III) protoporphyrin IX (K(d,app) = 6.5 × 10(-8) M), and lowers the redox potential of the cofactor to -172 mV. This work demonstrates that specific design features aimed at controlling the properties of bound cofactors can be introduced in a minimalist membrane hemoprotein model. The ability to modulate the redox potential of cofactors embedded in artificial membrane proteins is crucial for the design of electron transfer chains across membranes in functional photosynthetic devices. © SBIC 2012

  16. Comparison of approaches and artefacts in the measurement of detector modulation transfer functions

    Energy Technology Data Exchange (ETDEWEB)

    Boothroyd, C.B., E-mail: ChrisBoothroyd@cantab.net [Ernst Ruska-Centre and Peter Grünberg Institute, Forschungszentrum Jülich, D-52425 Jülich (Germany); Kasama, T. [Center for Electron Nanoscopy, Technical University of Denmark, DK-2800 Kongens Lyngby (Denmark); Dunin-Borkowski, R.E. [Ernst Ruska-Centre and Peter Grünberg Institute, Forschungszentrum Jülich, D-52425 Jülich (Germany)

    2013-06-15

    In order to investigate the reproducibility of measurements of transmission electron microscope detector modulation transfer functions (MTFs) we measure the MTF of a charge-coupled device (CCD) camera using five different methods. MTFs derived from a sharp edge, a circular aperture and electron holographic interference fringes are found to agree closely with one other. The difficulty of obtaining accurate measurements of MTFs and the potential of using focused electron probes to make direct measurements of MTFs is discussed. We highlight the sensitivity of image contrast after deconvolution to small differences in the measured MTF. - Highlights: ► The modulation transfer function (MTF) of a CCD camera is measured using five different methods. ► Only methods that involve the use of a sharp aperture or holographic interference fringes work well. ► The use of a focused spot promises to be the best method in the future if it can be focused small enough. ► Apparently small errors in the measurement of the MTF can have a large effect on deconvoluted images. ► MTFs must be measured accurately if images are to be compared quantitatively with simulations.

  17. Analogy of transistor function with modulating photonic band gap in electromagnetically induced grating.

    Science.gov (United States)

    Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng

    2015-09-09

    Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing.

  18. Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function.

    Directory of Open Access Journals (Sweden)

    Kasra Hassani

    Full Text Available Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS during transmission from the sandfly vector (ambient temperature, 25-26°C to the mammalian host (37°C. We have observed that this TS induces a rapid and dramatic increase in protein release from Leishmania mexicana (cutaneous leishmaniasis within 4 h. Proteomic identification of the TS-induced secreted proteins revealed 72 proteins, the majority of which lack a signal peptide and are thus thought to be secreted via nonconventional mechanisms. Interestingly, this protein release is accompanied by alterations in parasite morphology including an augmentation in the budding of exovesicles from its surface. Here we show that the exoproteome of L. mexicana upon TS induces cleavage and activation of the host protein tyrosine phosphatases, specifically SHP-1 and PTP1-B, in a murine bone-marrow-derived macrophage cell line. Furthermore, translocation of prominent inflammatory transcription factors, namely NF-κB and AP-1 is altered. The exoproteome also caused inhibition of nitric oxide production, a crucial leishmanicidal function of the macrophage. Overall, our results provide strong evidence that within early moments of interaction with the mammalian host, L. mexicana rapidly releases proteins and exovesicles that modulate signalling and function of the macrophage. These modulations can result in attenuation of the inflammatory response and deactivation of the macrophage aiding the parasite in the establishment of infection.

  19. An extensive investigation of work function modulated trapezoidal recessed channel MOSFET

    Science.gov (United States)

    Lenka, Annada Shankar; Mishra, Sikha; Mishra, Satyaranjan; Bhanja, Urmila; Mishra, Guru Prasad

    2017-11-01

    The concept of silicon on insulator (SOI) and grooved gate help to lessen the short channel effects (SCEs). Again the work function modulation along the metal gate gives a better drain current due to the uniform electric field along the channel. So all these concepts are combined and used in the proposed MOSFET structure for more improved performance. In this work, trapezoidal recessed channel silicon on insulator (TRC-SOI) MOSFET and work function modulated trapezoidal recessed channel silicon on insulator (WFM-TRC-SOI) MOSFET are compared with DC and RF parameters and later linearity of both the devices is tested. An analytical model is formulated by using a 2-D Poisson's equation and develops a compact equation for threshold voltage using minimum surface potential. In this work we analyze the effect of negative junction depth and the corner angle on various device parameters such as minimum surface potential, sub-threshold slope (SS), drain induced barrier lowering (DIBL) and threshold voltage. The analysis interprets that the switching performance of WFM-TRC-SOI MOSFET surpasses TRC-SOI MOSFET in terms of high Ion/Ioff ratio and also the proposed structure can minimize the short channel effects (SCEs) in RF application. The validity of proposed model has been verified with simulation result performed on Sentaurus TCAD device simulator.

  20. Effects of chronic administration of ethanolic extract of kolanut (Cola nitida) and caffeine on vascular function.

    Science.gov (United States)

    Salahdeen, H M; Omoaghe, A O; Isehunwa, G O; Murtala, B A; Alada, A R A

    2014-03-01

    Kolanut (Cola nitida) is consumed in virtually every part of the world. The caffeine content of kolanut is scarce and the number of investigations studying the health benefits of kolanut is negligible compared to coffee. The present study was designed to identify the caffeine content of kolanut and evaluate the effect of its chronic consumption on cardiovascular functions in rats. The caffeine content of kolanut was determined by Gas chromatography-mass spectrometry (GC-MS). Wistar albino rats were divided into four groups (10 Rats/group). Kolanut extract (11.9 mg/kg), caffeine extracted from kolanut (7.5 mg/kg), decaffeinated of kolanut extract (6 mg/kg) and distilled water (control) was administered orally to each group for six-weeks. Effect of treatment on body weight, blood pressure and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) of the aortic rings was assessed. The total caffeine content of kolanut extract was found to be 51% and it was 96% pure from GC-MS analysis. Chronic consumption of kolanut and caffeine significantly (p caffeine significantly (p caffeine also significantly (p Caffeine and kolanut consumption reduced the relaxation response to both acetylcholine and sodium nitroprusside. Atropine and L-NAME considerably inhibit the ACh-induced relaxation of the rat aortic ring suggesting the involvement of cholinergic mechanism. However, indomethacin (10(-4)M) also attenuated the ACh response indicating involvement of protanoids. The results suggest that treatment with both kolanut extract and caffeine had similar characteristics between the two groups with no significant differences in the ACh-induced relaxation of thering suggesting that the action of kolanut extract is due to its caffeine content.

  1. Development of a Kelp-Type Structure Module in a Coastal Ocean Model to Assess the Hydrodynamic Impact of Seawater Uranium Extraction Technology

    Directory of Open Access Journals (Sweden)

    Taiping Wang

    2014-02-01

    Full Text Available With the rapid growth of global energy demand, interest in extracting uranium from seawater for nuclear energy has been renewed. While extracting seawater uranium is not yet commercially viable, it serves as a “backstop” to the conventional uranium resources and provides an essentially unlimited supply of uranium resource. With recent technology advances, extracting uranium from seawater could be economically feasible only when the extraction devices are deployed at a large scale (e.g., several hundred km2. There is concern however that the large scale deployment of adsorbent farms could result in potential impacts to the hydrodynamic flow field in an oceanic setting. In this study, a kelp-type structure module based on the classic momentum sink approach was incorporated into a coastal ocean model to simulate the blockage effect of a farm of passive uranium extraction devices on the flow field. The module was quantitatively validated against laboratory flume experiments for both velocity and turbulence profiles.Model results suggest that the reduction in ambient currents could range from 4% to 10% using adsorbent farm dimensions and mooring densities previously described in the literature and with typical drag coefficients.

  2. Modulation of Functional Connectivity in Auditory-Motor Networks in Musicians Compared with Nonmusicians.

    Science.gov (United States)

    Palomar-García, María-Ángeles; Zatorre, Robert J; Ventura-Campos, Noelia; Bueichekú, Elisenda; Ávila, César

    2017-05-01

    Correlation of spontaneous fluctuations at rest between anatomically distinct brain areas are proposed to reflect the profile of individual a priori cognitive biases, coded as synaptic efficacies in cortical networks. Here, we investigate functional connectivity at rest (rs-FC) in musicians and nonmusicians to test for differences in auditory, motor, and audiomotor connectivity. As expected, musicians had stronger rs-FC between the right auditory cortex (AC) and the right ventral premotor cortex than nonmusicians, and this stronger rs-FC was greater in musicians with more years of practice. We also found reduced rs-FC between the motor areas that control both hands in musicians compared with nonmusicians, which was more evident in the musicians whose instrument required bimanual coordination and as a function of hours of practice. Finally, we replicated previous morphometric data to show an increased volume in the right AC in musicians, which was greater in those with earlier musical training, and that this anatomic feature was in turn related to greater rs-FC between auditory and motor systems. These results show that functional coupling within the motor system and between motor and auditory areas is modulated as a function of musical training, suggesting a link between anatomic and functional brain features. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Extracting the Green's function of attenuating heterogeneous acoustic media from uncorrelated waves.

    Science.gov (United States)

    Snieder, Roel

    2007-05-01

    The Green's function of acoustic or elastic wave propagation can, for loss-less media, be retrieved by correlating the wave field that is excited by random sources and is recorded at two locations. Here the generalization of this idea to attenuating acoustic waves in an inhomogeneous medium is addressed, and it is shown that the Green's function can be retrieved from waves that are excited throughout the volume by spatially uncorrelated injection sources with a power spectrum that is proportional to the local dissipation rate. For a finite volume, one needs both volume sources and sources at the bounding surface for the extraction of the Green's functions. For the special case of a homogeneous attenuating medium defined over a finite volume, the phase and geometrical spreading of the Green's function is correctly retrieved when the volume sources are ignored, but the attenuation is not.

  4. An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

    Science.gov (United States)

    Shin, In Sik; Lee, Mee Young; Lim, Hye Sun; Ha, Hyekyung; Seo, Chang Seob; Kim, Jong-Choon; Shin, Hyeun Kyoo

    2012-01-01

    Crataegus pinnatifida (Chinese hawthorn) has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE) on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP)-9, and other factors, using an ovalbumin (OVA)-induced murine asthma model. Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA) assays. Lung tissue sections 4 µm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility of CPEE as a therapeutic drug for allergic asthma.

  5. An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

    Directory of Open Access Journals (Sweden)

    In Sik Shin

    Full Text Available BACKGROUND: Crataegus pinnatifida (Chinese hawthorn has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP-9, and other factors, using an ovalbumin (OVA-induced murine asthma model. METHODS/PRINCIPAL FINDING: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF was collected 48 h after the final OVA challenge. Levels of interleukin (IL-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA assays. Lung tissue sections 4 µm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. CONCLUSIONS: These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility

  6. Ibogaine and a total alkaloidal extract of Voacanga africana modulate neuronal excitability and synaptic transmission in the rat parabrachial nucleus in vitro.

    Science.gov (United States)

    Kombian, S B; Saleh, T M; Fiagbe, N I; Chen, X; Akabutu, J J; Buolamwini, J K; Pittman, Q J

    1997-01-01

    Ibogaine is a natural alkaloid of Voacanga africana that is effective in the treatment of withdrawal symptoms and craving in drug addicts. As the synaptic and cellular basis of ibogaine's actions are not well understood, this study tested the hypothesis that ibogaine and Voacanga africana extract modulate neuronal excitability and synaptic transmission in the parabrachial nucleus using the nystatin perforated patch-recording technique. Ibogaine and Voacanga africana extract dose dependently, reversibly, and consistently attenuate evoked excitatory synaptic currents recorded in parabrachial neurons. The ED50 of ibogaine's effect is 5 microM, while that of Voacanga africana extract is 170 micrograms/ml. At higher concentrations, ibogaine and Voacanga africana extract induce inward currents or depolarization that are accompanied by increases in evoked and spontaneous firing rate. The depolarization or inward current is also accompanied by an increase in input resistance and reverses polarity around 0 mV. The depolarization and synaptic depression were blocked by the dopamine receptor antagonist haloperidol. These results indicate that ibogaine and Voacanga africana extract 1) depolarize parabrachial neurons with increased excitability and firing rate; 2) depress non-NMDA receptor-mediated fast synaptic transmission; 3) involve dopamine receptor activation in their actions. These results further reveal that the Voacanga africana extract has one-hundredth the activity of ibogaine in depressing synaptic responses. Thus, ibogaine and Voacanga africana extract may produce their central effects by altering dopaminergic and glutamatergic processes.

  7. Spray-drying microencapsulation of synergistic antioxidant mushroom extracts and their use as functional food ingredients.

    Science.gov (United States)

    Ribeiro, Andreia; Ruphuy, Gabriela; Lopes, José Carlos; Dias, Madalena Maria; Barros, Lillian; Barreiro, Filomena; Ferreira, Isabel C F R

    2015-12-01

    In this work, hydroalcoholic extracts of two mushrooms species, Suillus luteus (L.: Fries) (Sl) and Coprinopsis atramentaria (Bull.) (Ca), were studied for their synergistic antioxidant effect and their viability as functional food ingredients tested by incorporation into a food matrix (cottage cheese). In a first step, the individual extracts and a combination of both, showing synergistic effects (Sl:Ca, 1:1), were microencapsulated by spray-drying using maltodextrin as the encapsulating material. The incorporation of free extracts resulted in products with a higher initial antioxidant activity (t0) but declining after 7 days (t7), which was associated with their degradation. However, the cottage cheese enriched with the microencapsulated extracts, that have revealed a lower activity at the initial time, showed an increase at t7. This improvement can be explained by an effective protection provided by the microspheres together with a sustained release. Analyses performed on the studied cottage cheese samples showed the maintenance of the nutritional properties and no colour modifications were noticed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function

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    Xiao-Hui He

    2017-11-01

    Full Text Available Objective: To study the regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function. Methods: Osteoblasts MG-63 were cultured and divided into borosilicate group and control group that were treated with the culture medium containing borosilicate bioglass extract and the culture medium without extract respectively. After 24 h of treatment, the cell proliferation activity as well as the expression of proliferation activity markers, Wnt signaling pathway molecules and PI3K/ AKT signaling pathway molecules was measured. Results: After 24 h of treatment, MTT cell viability of borosilicate group was significantly higher than that of control group, and ALP, OC, OPN, COL-I, Runx2, Wnt1, Wnt3a, β-catenin, LRP5, LRP6, p-PI3K, p-AKT, Bcl-2 and BMP protein expression in cells were significantly higher than those of control group. Conclusion: Borosilicate bioglass extract can enhance the proliferation activity of osteoblasts by activating Wnt pathway and PI3K/AKT pathway.

  9. Achyrocline satureioides (Lam. D.C. Hydroalcoholic Extract Inhibits Neutrophil Functions Related to Innate Host Defense

    Directory of Open Access Journals (Sweden)

    Eric Diego Barioni

    2013-01-01

    Full Text Available Achyrocline satureioides (Lam. D.C. is a herb native to South America, and its inflorescences are popularly employed to treat inflammatory diseases. Here, the effects of the in vivo actions of the hydroalcoholic extract obtained from inflorescences of A. satureioides on neutrophil trafficking into inflamed tissue were investigated. Male Wistar rats were orally treated with A. satureioides extract, and inflammation was induced one hour later by lipopolysaccharide injection into the subcutaneous tissue. The number of leukocytes and the amount of chemotactic mediators were quantified in the inflammatory exudate, and adhesion molecule and toll-like receptor 4 (TLR-4 expressions and phorbol-myristate-acetate- (PMA- stimulated oxidative burst were quantified in circulating neutrophils. Leukocyte-endothelial interactions were quantified in the mesentery tissue. Enzymes and tissue morphology of the liver and kidney were evaluated. Treatment with A. satureioides extract reduced neutrophil influx and secretion of leukotriene B4 and CINC-1 in the exudates, the number of rolling and adhered leukocytes in the mesentery postcapillary venules, neutrophil L-selectin, β2-integrin and TLR-4 expression, and oxidative burst, but did not cause an alteration in the morphology and activities of liver and kidney. Together, the data show that A. satureioides extract inhibits neutrophil functions related to the innate response and does not cause systemic toxicity.

  10. Canarium ovatum Engl. (Pili exocarp crude extract as functional food colorant incorporated in yogurt developed product

    Directory of Open Access Journals (Sweden)

    Aril-dela Cruz, J.V.,

    2017-09-01

    Full Text Available Canarium ovatum Engl. (Pili, a locally grown plant in the Philippines, bears highly pigmented fruits. In this research study, the deeply pigmented fruit exocarp was evaluated for phytochemical contents, functional properties and possible application to yogurt as a colorant. Spectrophotometric analysis of the extract revealed high phenolic and flavonoid content, particularly anthocyanins (17.5 mg CE/g DW of the sample. The pigment extract also exhibited potential antioxidant activities as determined by DPPH and FRAP assays and did not show any inhibitory activity against gut normal flora, Escherichia coli, but also failed to express cytotoxic activity against HCT116 colon cancer cell line. Stability tests showed decreased redness with increasing temperature or pH. The pigment exhibited excellent color retention in yogurt during the two-week storage at 4oC. Sensory evaluation showed a slight difference in over-all acceptability between natural and synthetic-colored yogurt. Thus, Pili exocarp extract can be used as a functional food colorant in yogurt.

  11. Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb.

    Science.gov (United States)

    Kuzmina, Alona; Krasnopolsky, Simona; Taube, Ran

    2017-05-27

    Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear. Here we revisit the contribution of SEC in early steps of HIV gene transcription. In the absence of Tat, the AF4/FMR2 Family member 4 (AFF4) of SEC efficiently activates HIV transcription, while gene activation by its homolog AFF1 is substantially lower. Differential recruitment to the HIV promoter and association with Human Polymerase-Associated Factor complex (PAFc) play key role in this functional distinction between AFF4 and AFF1. Moreover, while depletion of cyclin T1 expression has subtle effects on HIV gene transcription in the absence of Tat, knockout (KO) of AFF1, AFF4, or both proteins slightly repress this early step of viral transcription. Upon Tat expression, HIV transcription reaches optimal levels despite KO of AFF1 or AFF4 expression. However, double AFF1/AFF4 KO completely diminishes Tat trans-activation. Significantly, our results show that P-TEFb phosphorylates AFF4 and modulates SEC assembly, AFF1/4 dimerization and recruitment to the viral promoter. We conclude that SEC promotes both early steps of HIV transcription in the absence of Tat, as well as elongation of transcription, when Tat is expressed. Significantly, SEC functions are modulated by P-TEFb.

  12. Electro-acupuncture at different acupoints modulating the relative specific brain functional network

    Science.gov (United States)

    Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

    2010-11-01

    Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

  13. Response inhibition is modulated by functional cerebral asymmetries for facial expression perception

    Directory of Open Access Journals (Sweden)

    Sebastian eOcklenburg

    2013-11-01

    Full Text Available The efficacy of executive functions is critically modulated by information processing in earlier cognitive stages. For example, initial processing of verbal stimuli in the language-dominant left-hemisphere leads to more efficient response inhibition than initial processing of verbal stimuli in the non-dominant right hemisphere. However, it is unclear whether this organizational principle is specific for the language system, or a general principle that also applies to other types of lateralized cognition. To answer this question, we investigated the neurophysiological correlates of early attentional processes, facial expression perception and response inhibition during tachistoscopic presentation of facial ‘Go’ and ‘Nogo’ stimuli in the left and the right visual field. Participants committed fewer false alarms after Nogo-stimulus presentation in the left compared to the right visual field. This right-hemispheric asymmetry on the behavioral level was also reflected in the neurophysiological correlates of face perception, specifically in a right-sided asymmetry in the N170 amplitude. Moreover, the right-hemispheric dominance for facial expression processing also affected event-related potentials typically related to response inhibition, namely the Nogo-N2 and Nogo-P3. These findings show that an effect of hemispheric asymmetries in early information processing on the efficacy of higher cognitive functions is not limited to left-hemispheric language functions, but can be generalized to predominantly right-hemispheric functions.

  14. Effect of calyx capsule-ethanol extract Hibiscus sabdariffa L. on renal function of healthy volunteers

    Science.gov (United States)

    Harun, N.; Darmawan, E.; Nurani, L. H.

    2017-11-01

    Hibiscus sabdariffa contains flavonoid, triterpenoid, anthocyanin which function as immunostimulant. H. sabdariffa is considered safe for animal renal; nonetheless, there are known side effects of which need to be further investigated for human renal. This research aims to investigate the effect of calyx capsule-ethanol extract H. sabdariffa for renal function of healthy male and female for 30 days period by monitoring Scr and Clcr component in their blood samples. The method of this experimental research was by pre and post-treatment by involving 20 healthy volunteers who have met inclusion and exclusion criteria. The volunteers have completed the informed consent for this experiment. Furthermore, volunteers were divided into two groups (10 male and 10 female). Each group was given orally 500 mg of calyx capsule-ethanol extract H. sabdariffa per day for 30 days period. Blood tests were taken on day 0, day 30 after consuming the capsule and day 45 (15 days after the last day of capsule intake) in order to measure the Scr and Clcr concentration in the blood samples by using Jaffe dan Cockcroft-Gault method. The results of each sampling day were further analyzed statistically and compared using Repeated ANOVA dan Friedman test. The results suggest that there was a difference in the renal function on day 0, 30 and 45 samplings. However, there was no significant difference in Scr dan Clcr concentrations on female and male volunteers (p>0.05). Specifically, the type of gender affects Scr concentration (p0.05). In addition, age and Body Mass Index (BMI) does not affect Scr and Clcr concentrations (p>0.05). The side effects discovered through the monitoring increased in mixturition and bloatedness. Calyx capsule-ethanol extract H. sabdariffa does not affect on renal function of healthy volunteers.

  15. Parameters extraction for perovskite solar cells based on Lambert W-function

    Directory of Open Access Journals (Sweden)

    Ge Junyu

    2016-01-01

    Full Text Available The behaviors of the solar cells are decided by the device parameters. Thus, it is necessary to extract these parameters to achieve the optimal working condition. Because the five-parameter model of solar cells has the implicit equation of current-voltage relationship, it is difficult to obtain the parameters with conventional methods. In this work, an optimized method is presented to extract device parameters from the actual test data of photovoltaic cell. Based on Lambert W-function, explicit formulation of the model can be deduced. The proposed technique takes suitable method of selecting sample points, which are used to calculate the values of the model parameters. By comparing with the Quasi-Newton method, the results verify accuracy and reliability of this method.

  16. Effect of methanol leaf extract of Dalbergia saxatilis Hook.f (fabaceae on renal function

    Directory of Open Access Journals (Sweden)

    Fatima Ismail Hassan

    2016-11-01

    Full Text Available Objective: Dalbegia saxatilis (D.saxatilis is used as a decoction in traditional medicine for ailments such as cough, small pox, skin lesions, bronchial ailments and toothache. This study is aimed at evaluating the toxic effect of methanol leaf extract of D.saxatilis on renal function. Materials and Methods: Wistar rats of both sexes were divided into four groups of five: control animals (group 1 received distilled water 1 ml/kg while groups 2, 3 and 4 were given graded doses of the extract (250, 500 and 1000 mg/kg body weight, respectively daily for 28 days. Body weight changes were estimated by weighing the rats twice weekly using digital weighing balance. After 28 days, blood samples were obtained for evaluation of renal indices and the kidney was used for histopathology. Data were analysed using one–way and repeated measures ANOVA using SPSS version 20. Results: Significant weight increase in all groups were observed (p

  17. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals

    Science.gov (United States)

    Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen® to modulate functional responses of ne...

  18. Chemical composition of Artemisia annua L. leaves and antioxidant potential of extracts as a function of extraction solvents

    National Research Council Canada - National Science Library

    Iqbal, Shahid; Younas, Umer; Chan, Kim Wei; Zia-Ul-Haq, Muhammad; Ismail, Maznah

    2012-01-01

    This study was conducted to investigate the chemical and nutritional composition of Artemisia annua leaves in addition to determination of antioxidant potential of their extracts prepared in different solvents...

  19. Menthol Suppresses Nicotinic Acetylcholine Receptor Functioning in Sensory Neurons via Allosteric Modulation

    Science.gov (United States)

    Wilhelm, M.; Swandulla, D.

    2012-01-01

    In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (−) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC50 of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC50 value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs. PMID:22281529

  20. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    Science.gov (United States)

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A1 receptors with 2-chloro-N6-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1 receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis. PMID:22552934

  1. Effects of scintillator on the modulation transfer function (MTF) of a digital imaging system.

    Science.gov (United States)

    Farman, Taeko T; Vandre, Robert H; Pajak, John C; Miller, Stuart R; Lempicki, Alex; Farman, Allan G

    2005-05-01

    To investigate the effects of 2 components (scintillator and x-ray generator) in the imaging chain on the modulation transfer function (MTF) of a charge-coupled device (CCD) digital intraoral radiographic system. Three screens composed of 3 different scintillator materials, namely europium-doped lutetium oxide transparent optical ceramic (TOC), thallium-doped cesium iodide (CsI), and terbium-doped gadolinium oxysulfide (GOS), were compared. Each was used, in turn, in conjunction with a CCD detector having a pixel dimension of 19.5 mum. Two different x-ray generators were also used to evaluate this variable. MTF was investigated using the slanted slit method. The TOC provided a good modulation response for low and middle frequencies, reducing to 0 only at a high cutoff frequency. With CsI and GOS, the system MTF dropped to 0 at a lower cutoff frequency than was the case with TOC. Hence, TOC provided higher spatial resolution than the other 2 scintillators tested under the experimental conditions applied. The differences in MTF attributed to the scintillator type were proportional and consistent. Despite constant pixel dimensions, MTF was affected to a considerable degree by the scintillator applied and the x-ray generator used in conjunction with the same CCD imaging device. TOC shows potential as a possible replacement for CsI and GOS as a scintillator screen material for intraoral digital x-ray imaging using a solid-state detector, providing higher spatial resolution under the given experimental conditions.

  2. Modulated modularity clustering as an exploratory tool for functional genomic inference.

    Science.gov (United States)

    Stone, Eric A; Ayroles, Julien F

    2009-05-01

    In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC), seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity) that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation.

  3. Modulation of α power and functional connectivity during facial affect recognition.

    Science.gov (United States)

    Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

    2013-04-03

    Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

  4. GenoQuery: a new querying module for functional annotation in a genomic warehouse

    Science.gov (United States)

    Lemoine, Frédéric; Labedan, Bernard; Froidevaux, Christine

    2008-01-01

    Motivation: We have to cope with both a deluge of new genome sequences and a huge amount of data produced by high-throughput approaches used to exploit these genomic features. Crossing and comparing such heterogeneous and disparate data will help improving functional annotation of genomes. This requires designing elaborate integration systems such as warehouses for storing and querying these data. Results: We have designed a relational genomic warehouse with an original multi-layer architecture made of a databases layer and an entities layer. We describe a new querying module, GenoQuery, which is based on this architecture. We use the entities layer to define mixed queries. These mixed queries allow searching for instances of biological entities and their properties in the different databases, without specifying in which database they should be found. Accordingly, we further introduce the central notion of alternative queries. Such queries have the same meaning as the original mixed queries, while exploiting complementarities yielded by the various integrated databases of the warehouse. We explain how GenoQuery computes all the alternative queries of a given mixed query. We illustrate how useful this querying module is by means of a thorough example. Availability: http://www.lri.fr/~lemoine/GenoQuery/ Contact: chris@lri.fr, lemoine@lri.fr PMID:18586731

  5. Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling

    Directory of Open Access Journals (Sweden)

    Young Woo Kim

    2014-10-01

    Full Text Available Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption.

  6. 3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression.

    Science.gov (United States)

    Lewis, Phillip L; Green, Richard M; Shah, Ramille N

    2018-01-06

    Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds. An undifferentiated hepatocyte cell line (HUH7) demonstrated high viability and proliferation when seeded on 3D-printed scaffolds of two different geometries. However, hepatocyte specific functions (albumin secretion, CYP activity, and bile transport) increases in more interconnected 3D-printed gelatin cultures compared to a less interconnected geometry and to 2D controls. Additionally, we also illustrate the disparity between gene expression and protein function in simple 2D culture modes, and that recreation of a physiologically mimetic 3D environment is necessary to induce both expression and function of cultured hepatocytes. Three dimensional (3D) printing provides tissue engineers the ability spatially pattern cells and materials in precise geometries, however the biological effects of scaffold geometry on soft tissues such as the liver have not been rigorously investigated. In this manuscript, we describe a method to 3D print gelatin into well-defined repetitive geometries that show clear differences in biological effects on seeded hepatocytes. We show that a relatively simple and widely used biomaterial, such as gelatin, can significantly modulate biological processes when fabricated into specific 3D geometries. Furthermore, this study expands upon past research into hepatocyte aggregation by demonstrating how it can be manipulated to enhance protein function, and how function and expression may not precisely correlate in

  7. Computational discovery of transcriptional regulatory modules in fungal ribosome biogenesis genes reveals novel sequence and function patterns.

    Science.gov (United States)

    Martyanov, Viktor; Gross, Robert H

    2013-01-01

    Genes involved in ribosome biogenesis and assembly (RBA) are responsible for ribosome formation. In Saccharomyces cerevisiae, their transcription is regulated by two dissimilar DNA motifs. We were interested in analyzing conservation and divergence of RBA transcription regulation machinery throughout fungal evolution. We have identified orthologs of S. cerevisiae RBA genes in 39 species across fungal phylogeny and searched upstream regions of these gene sets for DNA sequences significantly similar to S. cerevisiae RBA regulatory motifs. In addition to confirming known motif arrangements comprising two different motifs in a set of S. cerevisiae close relatives or two instances of the same motif (that we refer to as modules), we have also discovered novel modules in a group of fungi closely related to Neurospora crassa. Despite a single nucleotide difference between consensus sequences of RBA motifs, modules associated with S, cerevisiae group and N. crassa group displayed consistently different characteristics with respect to preferred module organization and several other module properties. For a given species, we have found a correlation between the configuration of the RBA module and significant enrichment in a set of specific Gene Ontology biological processes. We have identified several likely new candidates for a role in ribosome biogenesis in S. cerevisiae based on the combined evidence of RBA module presence in the upstream regions, functional annotation information and microarray expression profiles. We believe that this approach will be useful in terms of generating hypotheses about functional roles of genes for which only fragmentary data from a single source are available.

  8. Computational discovery of transcriptional regulatory modules in fungal ribosome biogenesis genes reveals novel sequence and function patterns.

    Directory of Open Access Journals (Sweden)

    Viktor Martyanov

    Full Text Available Genes involved in ribosome biogenesis and assembly (RBA are responsible for ribosome formation. In Saccharomyces cerevisiae, their transcription is regulated by two dissimilar DNA motifs. We were interested in analyzing conservation and divergence of RBA transcription regulation machinery throughout fungal evolution. We have identified orthologs of S. cerevisiae RBA genes in 39 species across fungal phylogeny and searched upstream regions of these gene sets for DNA sequences significantly similar to S. cerevisiae RBA regulatory motifs. In addition to confirming known motif arrangements comprising two different motifs in a set of S. cerevisiae close relatives or two instances of the same motif (that we refer to as modules, we have also discovered novel modules in a group of fungi closely related to Neurospora crassa. Despite a single nucleotide difference between consensus sequences of RBA motifs, modules associated with S, cerevisiae group and N. crassa group displayed consistently different characteristics with respect to preferred module organization and several other module properties. For a given species, we have found a correlation between the configuration of the RBA module and significant enrichment in a set of specific Gene Ontology biological processes. We have identified several likely new candidates for a role in ribosome biogenesis in S. cerevisiae based on the combined evidence of RBA module presence in the upstream regions, functional annotation information and microarray expression profiles. We believe that this approach will be useful in terms of generating hypotheses about functional roles of genes for which only fragmentary data from a single source are available.

  9. Evaluation of endoscopic vein extraction on structural and functional viability of saphenous vein endothelium

    Directory of Open Access Journals (Sweden)

    Lu Xiu-Gui

    2011-06-01

    Full Text Available Abstract Objectives Endothelial injury during harvest influences graft patency post CABG. We have previously shown that endoscopic harvest causes structural and functional damage to the saphenous vein (SV endothelium. However, causes of such injury may depend on the extraction technique. In order to assess this supposition, we evaluated the effect of VirtuoSaph endoscopic SV harvesting technique (VsEVH on structural and functional viability of SV endothelium using multiphoton imaging, biochemical and immunofluorescence assays. Methods Nineteen patients scheduled for CABG were prospectively identified. Each underwent VsEVH for one portion and "No-touch" open SV harvesting (OSVH for another portion of the SV. A two cm segment from each portion was immersed in GALA conduit preservation solution and transported overnight to our lab for processing. The segments were labeled with fluorescent markers to quantify cell viability, calcium mobilization and generation of nitric oxide. Morphology, expression, localization and stability of endothelial caveolin, eNOS, von Willebrand factor and cadherin were evaluated using immunofluorescence, Western blot and multiphoton microscopy (MPM. Results Morphological, biochemical and immunofluorescence parameters of viability, structure and function were well preserved in VsEVH group as in OSVH group. However, tonic eNOS activity, agonist-dependent calcium mobilization and nitric oxide production were partially attenuated in the VsEVH group. Conclusions This study indicates that VirtuoSaph endoscopic SV harvesting technique preserves the structural and functional viability of SV endothelium, but may differentially attenuate the vasomotor function of the saphenous vein graft. Ultramini-Abstract Endoscopic extraction preserved the structure and function, but attenuated the calcium mobilization and nitric oxide generation in human SV endothelium.

  10. Spirodela polyrhiza extract modulates the activation of atopic dermatitis-related ion channels, Orai1 and TRPV3, and inhibits mast cell degranulation.

    Science.gov (United States)

    Nam, Joo Hyun; Jung, Hyo Won; Chin, Young-Won; Yang, Won-Mo; Bae, Hyo Sang; Kim, Woo Kyung

    2017-12-01

    Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash. The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated. The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100 μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100 μg/mL SH extract. SH extract (100 μg/mL) significantly inhibited Orai1 activity (63.8 ± 0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29 ± 0.05% at -100 mV) compared with the positive control 2-APB (100 μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14 ± 0.03, 2.56 ± 0.12 and 2.29 ± 0.08 mU/mg, respectively). Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.

  11. Acupuncture using laser needles modulates brain function: first evidence from functional transcranial Doppler sonography and functional magnetic resonance imaging.

    Science.gov (United States)

    Litscher, G; Rachbauer, D; Ropele, S; Wang, L; Schikora, D; Fazekas, F; Ebner, F

    2004-01-01

    Acupuncture using laser needles is a new totally painless stimulation method which has been described for the first time. This paper presents an experimental double-blind study in acupuncture research in healthy volunteers using a new optical stimulation method. We investigated 18 healthy volunteers (mean age +/- SD: 25.4 +/- 4.3 years; range: 21-30 years; 11 female, 7 male) in a randomized controlled cross-over trial using functional multidirectional transcranial ultrasound Doppler sonography (fTCD; n = 17) and performed functional magnetic resonance imaging (fMRI) in one volunteer. Stimulation of vision-related acupoints resulted in an increase of mean blood flow velocity in the posterior cerebral artery measured by fTCD [before stimulation (mean +/- SE): 42.2 +/- 2.5; during stimulation: 44.2 +/- 2.6; after stimulation: 42.3 +/- 2.4 cm/s, n.s.]. Mean blood flow velocity in the middle cerebral artery decreased insignificantly. Significant changes (p < 0.05) of brain activity were demonstrated in the occipital and frontal gyrus by fMRI. Optical stimulation using properly adjusted laser needles has the advantage that the stimulation cannot be felt by the patient (painless and no tactile stimulation) and the operator may also be unaware of whether the stimulation system is active. Therefore true double-blind studies in acupuncture research can be performed.

  12. The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants

    Directory of Open Access Journals (Sweden)

    Xiangmei Liu

    2016-09-01

    Full Text Available Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.

  13. An ATP-competitive inhibitor modulates the allosteric function of the HER3 pseudokinase

    Science.gov (United States)

    Littlefield, Peter; Moasser, Mark M.; Jura, Natalia

    2014-01-01

    The human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that lacks catalytic activity, but is essential for cellular homeostasis due to its ability to allosterically activate EGFR/HER2. Though catalytically inactive, HER3 binds ATP tightly, hinting at a possible role of the nucleotide-binding pocket in modulating HER3 function. We report a structure of the HER3 pseudokinase bound to the ATP-competitive inhibitor bosutinib. Previously solved structures show that bosutinib can potently interact with multiple kinase domain conformations. In complex with HER3, bosutinib binds to yet another conformation, which is nearly identical to that observed in the HER3/ATP complex. Interestingly, occupation of the ATP-binding site by bosutinib improves the ability of HER3 to act as an allosteric activator of EGFR in vitro by increasing the affinity of the HER3/EGFR heterodimer in a membrane-dependent manner. PMID:24656791

  14. The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation.

    Science.gov (United States)

    Bow, Eric W; Rimoldi, John M

    2016-01-01

    The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (-)-Δ(9)-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure-CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure-activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure-activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles.

  15. Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function

    Directory of Open Access Journals (Sweden)

    Oleg O. Glebov

    2017-03-01

    Full Text Available The active zone (AZ matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery. Conversely, patterned optogenetic stimulation of postsynaptic neurons retrogradely enhanced AZ clustering. In individual synapses, AZ clustering was inversely correlated with local VGCC recruitment and vesicle cycling. Acute actin depolymerization led to rapid (5 min nanoscale AZ matrix unclustering. We propose a model whereby neuronal activity modulates presynaptic function in a homeostatic manner by altering the clustering state of the AZ matrix.

  16. Numerical simulation of the modulation transfer function in planar InGaAs dense arrays

    Science.gov (United States)

    Bai, Lin; Xu, Yun; Jiang, Yu; Chen, Huamin; Wu, Haoyue; Zhang, Jiushuang; Song, Guofeng

    2017-09-01

    Three-dimensional simulation methodology has been used to evaluate the performance of lattice matched InGaAs/InP double layer planar heterointerface detector arrays. The device characteristics under optical illumination and dark conditions have been computed. The modulation transfer function (MTF) profiles have been calculated with varying device geometries and carrier dynamics. It is found that the p well diffusion radius and minority carrier recombination play important roles in the MTF behaviors of dense arrays. Moderate p well diffusion dimension should be used to balance the device performances between the dark current and MTF profile. Moreover, better MTF characteristic under low light condition can be achieved with higher quality material which has longer recombination lifetime. The influences of underlying mechanisms including photon generated carriers diffusion and carrier recombination processes have been discussed. These simulation methods and results should provide a useful tool for the evaluation and improvement of imaging power of InGaAs focal plane arrays.

  17. A miniature cadmium telluride detector module for continuous monitoring of left-ventricular function.

    Science.gov (United States)

    Hoffer, P B; Berger, H J; Steidley, J; Brendel, A F; Gottschalk, A; Zaret, B L

    1981-02-01

    The authors describe a miniature cadmium telluride (CdTe) detector module for continuous monitoring of ventricular function using an equilibrium radionuclide blood-pool label. The detector and collimator are small, light, and suitable for direct attachment to the chest wall. Clinical studies in 18 patients using a prototype system demonstrated reasonably good correlation with left-ventricular ejection fractions (LVEF) determined by first-pass studies performed with a multicrystal scintillation camera (r = 0.74) and gated equilibrium studies performed with a computerized sodium iodide (Nal) probe (r = 0.76). The CdTe device may prove to be useful in patients in intensive and coronary care units as well as in ambulatory patients.

  18. Evaluation of the modulation transfer function for computer tomography by using American Association Physics Medicine Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Won [Dept. of Radiology, Kyung Hee University Hospital at Gang-dong, Seoul (Korea, Republic of); Choi, Kwan Woo [Dept. of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Jeong, Hoi Woun [Dept. of Radiological Technology, Baekseok Culture University, Cheonan (Korea, Republic of); Jang, Seo Goo [Dept. of Medical Science, Soonchunhyang University, Asan (Korea, Republic of); Kwon, Kyung Tae [Dept. of Radiological Technology, Dongnam Health University, Suwon (Korea, Republic of); Son, Soon Yong [Dept. of Radiological Technology, Wonkwang Health Science University, Iksan (Korea, Republic of); Son, Jin Hyun; Min, Jung Whan [Dept. of Radiological Technology, Shingu University, Sungnam (Korea, Republic of)

    2016-06-15

    In clinical computed tomography (CT), regular quality assurance (QA) has been required. This study is to evaluate the MTF for analyzing the spatial resolution using AAPM phantom in CT exam. The dual source somatom definition flash (siemens healthcare, forchheim, Germany), the brilliance 64 (philips medical system Netherlands) and aquilion 64 (toshiba medical system, Japan) were used in this study. The quantitative evaluation was performed using the image J (wayne rasband national institutes of health, USA) and chart method which is measurement of modulation transfer function (MTF). In MTF evaluation, the spatial frequencies corresponding to the 50% MTF for the CT systems were 0.58, 0.28, and 0.59 mm-1, respectively and the 10% MTF for the CT systems were 1.63, 0.89, and 1.21 mm-1, respectively. This study could evaluate the characteristic of spatial resolution of MTF using chart method, suggesting the quantitative evaluation method using the data.

  19. Estimation of Multiple Point Sources for Linear Fractional Order Systems Using Modulating Functions

    KAUST Repository

    Belkhatir, Zehor

    2017-06-28

    This paper proposes an estimation algorithm for the characterization of multiple point inputs for linear fractional order systems. First, using polynomial modulating functions method and a suitable change of variables the problem of estimating the locations and the amplitudes of a multi-pointwise input is decoupled into two algebraic systems of equations. The first system is nonlinear and solves for the time locations iteratively, whereas the second system is linear and solves for the input’s amplitudes. Second, closed form formulas for both the time location and the amplitude are provided in the particular case of single point input. Finally, numerical examples are given to illustrate the performance of the proposed technique in both noise-free and noisy cases. The joint estimation of pointwise input and fractional differentiation orders is also presented. Furthermore, a discussion on the performance of the proposed algorithm is provided.

  20. Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes

    Science.gov (United States)

    Senbagavalli, P.; Hilda, J. Nancy; Ramanathan, V. D.; Kumaraswami, V.; Nutman, Thomas B.

    2012-01-01

    Circulating immune complexes (ICs) are associated with the pathogenesis of several diseases. Very little is known about the effect of ICs on the host immune response in patients with tuberculosis (TB). The effects of ICs isolated from patients with TB in modulating the release of calcium, cytokines, and granular proteins were studied in normal granulocytes, as were their chemotactic, phagocytic, and oxidative burst processes. ICs from TB patients induced decreased production of cytokines and platelet-activating factor (PAF) from normal granulocytes. ICs from TB patients also induced enhanced chemotaxis and phagocytosis but caused diminished oxidative burst. This was accompanied by an increased release in intracellular calcium. On the other hand, ICs from TB patients induced increased release of the granular proteins human neutrophil peptides 1 to 3 (HNP1–3). Thus, ICs from patients with TB exhibit a profound effect on granulocyte function with activation of certain effector mechanisms and dampening of others. PMID:23100480

  1. Dragon's Blood extract has antithrombotic properties, affecting platelet aggregation functions and anticoagulation activities.

    Science.gov (United States)

    Xin, Nian; Li, Yu-Juan; Li, Yan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Schlappi, Michael; Deng, Yu-Lin

    2011-05-17

    Dragon's Blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragon's Blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments. A rat/mouse thrombosis and blood stasis model was developed for this study, and EA and PB effects on thrombosis, platelet functions and blood coagulation activities were analyzed. It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on thrombosis (p<0.05), platelet aggregation function (p<0.01) and anticoagulation activity (p<0.05-0.01). The results obtained here showed that EA fraction from Dragon's Blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and anticoagulation activity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells.

    Science.gov (United States)

    Sparks, Avis E; Chen, Chiachen; Breslin, Mary B; Lan, Michael S

    2016-05-20

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells*

    Science.gov (United States)

    Sparks, Avis E.; Chen, Chiachen; Breslin, Mary B.; Lan, Michael S.

    2016-01-01

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity. PMID:27048654

  4. Ulipristal acetate modulates the expression and functions of activin a in leiomyoma cells.

    Science.gov (United States)

    Ciarmela, Pasquapina; Carrarelli, Patrizia; Islam, Md Soriful; Janjusevic, Milijana; Zupi, Errico; Tosti, Claudia; Castellucci, Mario; Petraglia, Felice

    2014-09-01

    Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age and represents the single most common indication for hysterectomy. A development of new treatments is necessary for a medical management, and in this direction, several hormonal drugs are under investigation. Ulipristal acetate (UPA; a selective progesterone receptor modulator) is considered as one of the most promising because progesterone has a critical role in development and growth of uterine leiomyoma. The effect of steroids is partly mediated by growth factors like activin A which increases extracellular matrix expression contributing to the growth of leiomyoma. The present study aimed to test whether UPA acts on leiomyoma cells affecting expression and functions of activin A system. Cultured myometrial and leiomyoma cells were treated with UPA, and messenger RNA (mRNA) expression levels of activin A (inhibin βA [INHBA] subunits), its binding proteins (follistatin [FST] and FST-related gene), and its receptors (activin receptor-like kinase 4 [ALK4], activin receptor type [ActR] II, and ActRIIB) were evaluated. The effect of UPA on activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells was also studied. Ulipristal acetate decreased INHBA, FST, ActRIIB, and Alk4 mRNA expressions in leiomyoma cultured cells. In addition, UPA was able to block the activin A-induced increase in fibronectin or VEGF-A mRNA expression in myometrial and in leiomyoma cultured cells. The present data show that UPA inhibits activin A expression and functions in leiomyoma cells, and this may represent a possible mechanism of action of the drug on uterine leiomyoma. © The Author(s) 2014.

  5. The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Laura Nocito

    Full Text Available Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB/acetoacetate (Acoc, reduced glutathione (GSH/oxidized glutathione (GSSG, and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(PH and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

  6. Detector level ABI spectral response function: FM4 analysis and comparison for different ABI modules

    Science.gov (United States)

    Efremova, Boryana; Pearlman, Aaron J.; Padula, Frank; Wu, Xiangqian

    2016-09-01

    A new generation of imaging instruments Advanced Baseline Imager (ABI) is to be launched aboard the Geostationary Operational Environmental Satellites - R Series (GOES-R). Four ABI flight modules (FM) are planned to be launched on GOES-R,S,T,U, the first one in the fall of 2016. Pre-launch testing is on-going for FM3 and FM4. ABI has 16 spectral channels, six in the visible/near infrared (VNIR 0.47 - 2.25 μm), and ten in the thermal infrared (TIR 3.9 - 13.3 μm) spectral regions, to be calibrated on-orbit by observing respectively a solar diffuser and a blackbody. Each channel has hundreds of detectors arranged in columns. Operationally one Analytic Generation of Spectral Response (ANGEN) function will be used to represent the spectral response function (SRF) of all detectors in a band. The Vendor conducted prelaunch end-to-end SRF testing to compare to ANGEN; detector specific SRF data was taken for: i) best detector selected (BDS) mode - for FM 2,3, and 4; and ii) all detectors (column mode) - for four spectral bands in FM3 and FM4. The GOES-R calibration working group (CWG) has independently used the SRF test data for FM2 and FM3 to study the potential impact of detector-to-detector SRF differences on the ABI detected Earth view radiances. In this paper we expand the CWG analysis to include the FM4 SRF test data - the results are in agreement with the Vendor analysis, and show excellent instrument performance and compare the detector-to-detector SRF differences and their potential impact on the detected Earth view radiances for all of the tested ABI modules.

  7. [A method of measuring presampled modulation transfer function using a rationalized approximation of geometrical edge slope].

    Science.gov (United States)

    Honda, Michitaka

    2014-04-01

    Several improvements were implemented in the edge method of presampled modulation transfer function measurements (MTFs). The estimation technique for edge angle was newly developed by applying an algorithm for principal components analysis. The error in the estimation was statistically confirmed to be less than 0.01 even in the presence of quantum noise. Secondly, the geometrical edge slope was approximated using a rationalized number, making it possible to obtain an oversampled edge response function (ESF) with equal intervals. Thirdly, the final MTFs were estimated using the average of multiple MTFs calculated for local areas. This averaging operation eliminates the errors caused by the rationalized approximation. Computer-simulated images were used to evaluate the accuracy of our method. The relative error between the estimated MTF and the theoretical MTF at the Nyquist frequency was less than 0.5% when the MTF was expressed as a sinc function. For MTFs representing an indirect detector and phase-contrast detector, good agreement was also observed for the estimated MTFs for each. The high accuracy of the MTF estimation was also confirmed, even for edge angles of around 10 degrees, which suggests the potential for simplification of the measurement conditions. The proposed method could be incorporated into an automated measurement technique using a software application.

  8. A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function.

    Science.gov (United States)

    Ramachandran, Kapil V; Margolis, Seth S

    2017-04-01

    In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It is unclear how proteasomes are able to acutely regulate such processes, as this action is inconsistent with their canonical role in proteostasis. Here we describe a mammalian nervous-system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is closely associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of the membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked the production of extracellular peptides and attenuated neuronal-activity-induced calcium signaling. Moreover, we observed that membrane-proteasome-derived peptides were sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes function primarily to maintain proteostasis, and highlight a form of neuronal communication that takes place through a membrane proteasome complex.

  9. Modulation of Intestinal Functions Following Mycotoxin Ingestion: Meta-Analysis of Published Experiments in Animals

    Science.gov (United States)

    Grenier, Bertrand; Applegate, Todd J.

    2013-01-01

    Mycotoxins are secondary metabolites of fungi that can cause serious health problems in animals, and may result in severe economic losses. Deleterious effects of these feed contaminants in animals are well documented, ranging from growth impairment, decreased resistance to pathogens, hepato- and nephrotoxicity to death. By contrast, data with regard to their impact on intestinal functions are more limited. However, intestinal cells are the first cells to be exposed to mycotoxins, and often at higher concentrations than other tissues. In addition, mycotoxins specifically target high protein turnover- and activated-cells, which are predominant in gut epithelium. Therefore, intestinal investigations have gained significant interest over the last decade, and some publications have demonstrated that mycotoxins are able to compromise several key functions of the gastrointestinal tract, including decreased surface area available for nutrient absorption, modulation of nutrient transporters, or loss of barrier function. In addition some mycotoxins facilitate persistence of intestinal pathogens and potentiate intestinal inflammation. By contrast, the effect of these fungal metabolites on the intestinal microbiota is largely unknown. This review focuses on mycotoxins which are of concern in terms of occurrence and toxicity, namely: aflatoxins, ochratoxin A and Fusarium toxins. Results from nearly 100 published experiments (in vitro, ex vivo and in vivo) were analyzed with a special attention to the doses used. PMID:23430606

  10. Accurate evaluation of modulation transfer function using the Fourier shift theorem

    Science.gov (United States)

    Kim, Yong Gwon; Ryu, Yeunchul

    2017-12-01

    Accurate determination of the line spread function (LSF) on the basis of the edge processing algorithm in X-ray imaging systems is one of the most basic procedures for evaluating the performance of such systems. Extensive research has been focused on algorithms for the precise or fast measurement of the LSF in digital X-ray systems. Most of the standard methods for evaluating the performance of an imaging system are based on a fully digitalized radiographic system or a film-based system. However, images obtained by computed radiography (CR), which converts a captured analog signal into a digital image through an analog-to-digital converting scanner, show the combined characteristics of analog and digital imaging systems. Fundamentally, the characteristics of digital imaging systems differ substantially from those of film imaging systems because of their different methods of acquiring and displaying image data. In addition, a system with both analog and digital component has characteristics that differ from those of both digital and analog systems. In this research, we present a new modulation transfer function (MTF) that mimics the existing MTF in terms of measurement but satisfies existing standard protocols through modification of the hypothesis contents. In the case of the LSF and the point spread function measured with a CR system, the developed edge algorithm shows better performance than the conventional methods. We also demonstrate the usefulness of this method in an actual measurement with a CR digital X-ray imaging system.

  11. p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

    Science.gov (United States)

    Deng, Wen; Zhou, Yuan; Tiwari, Agnes FY; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie LM; Guan, Xin-Yuan; Tsao, Sai Wah

    2015-01-01

    Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. PMID:25131797

  12. Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2.

    Science.gov (United States)

    Pflieger, Lance T; Dansithong, Warunee; Paul, Sharan; Scoles, Daniel R; Figueroa, Karla P; Meera, Pratap; Otis, Thomas S; Facelli, Julio C; Pulst, Stefan M

    2017-08-15

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice versus wild-type (WT) littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes. Our analysis revealed previously uncharacterized early and progressive abnormal patterning of cerebellar gene expression. Weighted Gene Coexpression Network Analysis revealed four gene modules that were significantly correlated with disease status, composed primarily of genes associated with GTPase signaling, calcium signaling and cell death. Of these genes, few overlapped with differentially expressed cerebellar genes that we identified in Atxn2-/- knockout mice versus WT littermates, suggesting that loss-of-function is not a significant component of disease pathology. We conclude that SCA2 is a disease characterized by gain of function for ATXN2. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Molecular basis for the electric field modulation of cytochrome C structure and function.

    Science.gov (United States)

    De Biase, Pablo M; Paggi, Damián Alvarez; Doctorovich, Fabio; Hildebrandt, Peter; Estrin, Dario A; Murgida, Daniel H; Marti, Marcelo A

    2009-11-11

    Cytochrome c (Cyt) is a small soluble heme protein with a hexacoordinated heme and functions as an electron shuttle in the mitochondria and in early events of apoptosis when released to the cytoplasm. Using molecular dynamics simulations, we show here that biologically relevant electric fields induce an increased mobility and structural distortion of key protein segments that leads to the detachment of the sixth axial ligand Met80 from the heme iron. This electric-field-induced conformational transition is energetically and entropically driven and leads to a pentacoordinated high spin heme that is characterized by a drastically lowered reduction potential as well as by an increased peroxidase activity. The simulations provide a detailed atomistic picture of the structural effects of the electric field on the structure of Cyt, which allows a sound interpretation of recent experimental results. The observed conformational change may modulate the electron transfer reactions of Cyt in the mitochondria and, furthermore, may constitute a switch from the redox function in the respiratory chain to the peroxidase function in the early events of apoptosis.

  14. Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats.

    Science.gov (United States)

    Pérez-Torres, Israel; Torres-Narváez, Juan Carlos; Pedraza-Chaverri, José; Rubio-Ruiz, María Esther; Díaz-Díaz, Eulises; Del Valle-Mondragón, Leonardo; Martínez-Memije, Raúl; Varela López, Elvira; Guarner-Lans, Verónica

    2016-10-26

    The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats (30% sucrose in drinking water from weaning) plus saline solution (MS + SS), control rats receiving AGE (C + AGE 125 mg/Kg/12 h) and MS rats with AGE (MS + AGE) were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p properties.

  15. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

    Science.gov (United States)

    Terao, Junji

    2017-09-01

    Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Interleukin-21 induces proliferation and modulates receptor expression and effector function in canine natural killer cells.

    Science.gov (United States)

    Shin, Dong-Jun; Lee, Soo-Hyeon; Park, Ji-Yun; Kim, Ju-Sun; Lee, Je-Jung; Suh, Guk-Hyun; Lee, Youn-Kyung; Cho, Duck; Kim, Sang-Ki

    2015-05-15

    Interleukin (IL)-21 is an important modulator of natural killer (NK) cell function. However, little is known about IL-21 function in canine NK cells because the phenotype of these cells remains undefined. In this study, we selectively expanded non-B and non-T large granular NK lymphocytes (CD3(-)CD21(-)CD5(-)CD4(-)TCRαβ(-)TCRγδ(-)) ex vivo from the peripheral blood mononuclear cells (PBMCs) of healthy dogs using a combination of IL-2, IL-15, and IL-21 in the presence of 100 Gy-irradiated K562 cells. We investigated the effects of varying the duration and timing of IL-21 treatment on stimulation of proliferation, expression of NK-related receptors, anti-tumor activity and production of interferon (IFN)-γ. The expanded NK cells in each treatment group became enlarged and highly granular after 21 days in culture. NK cells proliferated rapidly in response to activation by IL-21 for 3 weeks, and IL-21 was able to induce changes in the mRNA expression of NK cell-related receptors and enhance the effector function of NK cells in perforin- and granzyme-B-dependent manners. The duration, frequency and timing of IL-21 stimulation during culture affected the rate of proliferation, patterns of receptor expression, cytokine production, and anti-tumor activity. The optimal conditions for maximizing the IL-21-induced proliferation and effector function of NK cells in the presence of IL-2 and IL-15 were seen in cells treated with IL-21 for the first 7 days of culture but without any further IL-21 stimulation other than an additional 2-day treatment prior to harvesting on day 21. The results of this study suggest that synergistic interactions of IL-21 with IL-2 and IL-15 play an important role in the proliferation, receptor expression, and effector function of canine NK cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Atypical modulation of distant functional connectivity by cognitive state in children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Xiaozhen eYou

    2013-08-01

    Full Text Available We examined whether modulation of functional connectivity by cognitive state differed between pre-adolescent children with Autism Spectrum Disorders (ASD and age and IQ-matched control children. Children underwent functional magnetic resonance imaging (fMRI during two states, a resting state followed by a sustained attention task. A voxel-wise method was used to characterize functional connectivity at two levels, local (within a voxel’s 14 mm neighborhood and distant (outside of the voxel’s 14 mm neighborhood to the rest of the brain and regions exhibiting Group X State interaction were identified for both types of connectivity maps. Distant functional connectivity of regions in the left frontal lobe (dorsolateral [BA 11, 10]; supplementary motor area extending into dorsal anterior cingulate [BA 32/8]; and premotor [BA 6, 8, 9], right parietal lobe (paracentral lobule [BA 6 ]; angular gyrus [BA 39/40], and left posterior middle temporal cortex (BA 19/39 showed a Group X State interaction such that relative to the resting state, connectivity reduced (i.e., became focal in control children but increased (i.e., became diffuse in ASD children during the task state. Higher state-related increase in distant connectivity of left frontal and right angular gyrus predicted worse inattention in ASD children. Two graph theory measures (global efficiency and modularity were also sensitive to Group X State differences, with the magnitude of state-related change predicting inattention in the ASD children. Our results indicate that as ASD children transition from an unconstrained to a sustained attentional state, functional connectivity of frontal and parietal regions with the rest of the brain becomes more widespread in a manner that may be maladaptive as it was associated with attention problems in everyday life.

  18. Mental Task Classification Scheme Utilizing Correlation Coefficient Extracted from Interchannel Intrinsic Mode Function

    Directory of Open Access Journals (Sweden)

    Md. Mostafizur Rahman

    2017-01-01

    Full Text Available In view of recent increase of brain computer interface (BCI based applications, the importance of efficient classification of various mental tasks has increased prodigiously nowadays. In order to obtain effective classification, efficient feature extraction scheme is necessary, for which, in the proposed method, the interchannel relationship among electroencephalogram (EEG data is utilized. It is expected that the correlation obtained from different combination of channels will be different for different mental tasks, which can be exploited to extract distinctive feature. The empirical mode decomposition (EMD technique is employed on a test EEG signal obtained from a channel, which provides a number of intrinsic mode functions (IMFs, and correlation coefficient is extracted from interchannel IMF data. Simultaneously, different statistical features are also obtained from each IMF. Finally, the feature matrix is formed utilizing interchannel correlation features and intrachannel statistical features of the selected IMFs of EEG signal. Different kernels of the support vector machine (SVM classifier are used to carry out the classification task. An EEG dataset containing ten different combinations of five different mental tasks is utilized to demonstrate the classification performance and a very high level of accuracy is achieved by the proposed scheme compared to existing methods.

  19. EXTRACTION OF STRONTIUM(II BY CROWN ETHER: INSIGHTS FROM DENSITY FUNCTIONAL CALCULATION

    Directory of Open Access Journals (Sweden)

    Saprizal Hadisaputra

    2012-12-01

    Full Text Available The structures, energetic and thermodynamic parameters of crown ethers with different cavity size, electron donating/withdrawing substituent groups and donor atoms have been determined with density functional method at B3LYP level of theory in gas and solvent phase. Small core quasi-relativistic effective core potentials was used together with the accompanying SDD basis set for Sr2+ and DZP basis set was used for crown ether atoms. Natural bond orbital (NBO analysis was evaluated to characterize the distribution of electrons on the complexes. The interaction energy is well correlated with the values of Strontium charge after complexation, the second order interaction energies (E2 and HOMO-LUMO energy gab (∆Egab. The interaction energy and thermodynamics parameters in gas phase are reduced in solvent phase as the solvent molecules weaken the metal-crown ether interaction. The thermodynamic parameters indicated that less feasibility to extract Sr2+ ion directly from pure water without presence of organic solvent. The theoretical values of extraction energy for Sr(NO32 salt from aqueous solution in different organic solvent is validated by the experimental trend. This study would have strong contribution in planning the experiments to the design of specific host ligand and screening of solvent for extraction of metal ion.

  20. Disks solid phase extraction based polypyrrole functionalized core-shell nanofibers mat.

    Science.gov (United States)

    Qi, FeiFei; Li, XiaoQing; Yang, BiYi; Rong, Fei; Xu, Qian

    2015-11-01

    A novel disks solid phase extraction (SPE) based on polypyrrole (PPy) functionalized core-shell electrospun nanofibers mat was proposed. The performance of the established disks SPE technique was evaluated in the extraction of trace polar analytes from environmental water samples. Disulphonated (acid yellow 9) and monosulphonated azo dyes (acid orange 7 and metanil yellow) were selected as typical model analytes. Under the optimum conditions, detection limits were 0.15-0.3 μg/L for all target analytes and the enrichment coefficients were 106-121. The recoveries of sulfonated azo dyes added to typical environmental water samples were 87.6-112.3%, suggesting that the interferences of the sample matrix did not affect the enrichment. Compared with existing methods, the device in this study showed higher recovery, lower detection limit and better precision. Moreover, the miniaturized disks SPE technique for sample preparation is simple and fast, with significantly reduced sorbent bed mass (2.5 mg) and eluent volume (500 μL). These results indicate that PPy nanofibers mat-based disks SPE may be a promising device that can effectively extract the polar species in water samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2014-10-28

    In Thai traditional medicine, rhizomes of Kaempferia parviflora (KP) have been used for treating hypertension and for the promotion of longevity with good health and well being. Ageing is one of the most important risk factors for development of cardiovascular disease. To investigate whether a 6 weeks oral administration of a dichloromethane extract of fresh rhizomes of Kaempferia parviflora (KPD) had any effects on vascular functions, on the accumulation of lipid, as well as on any signs of gross organ toxicity in middle-aged rats. Fresh rhizomes of Kaempferia parviflora were first macerated twice with 95% ethanol to remove the dark color before extracting three times with 100% dichloromethane. The dichloromethane extract was evaporated under reduced pressure to obtain the dried Kaempferia parviflora dichloromethane extract (KPD). The rats were orally administered with the KPD at a dosage of 100mg/kg body weight, or with the same volume of the vehicle (tween 80, 0.2g: carboxy-methylcellulose sodium, 0.2g: distilled water 10 ml) once or twice a day for 6 weeks. Vascular functions were studied on isolated thoracic aorta and the mesenteric artery. The vascular eNOS enzyme was measured by Western blot analysis. Blood chemistry was measured by enzymatic methods. Liver cell lipid accumulation was measured using oil red O staining. A 6 weeks treatment of KPD once a day had no significant effects on any of the studied parameters. When the KPD was given twice a day, the contractile responses to phenylephrine of the thoracic aorta and mesenteric artery were lower than the vehicle control group, and this effect was abolished by N(G)-nitro-l-arginine or by removal of the vascular endothelium. Vasorelaxation to acetylcholine, but not to glyceryl trinitrate, by the thoracic aortic and mesenteric ring precontracted with phenylephrine was higher from the KPD treated rats than those from the vehicle control groups. Western blot analysis showed a higher quantity of thoracic- and

  2. Extraction of triazole fungicides in environmental waters utilizing poly (ionic liquid)-functionalized magnetic adsorbent.

    Science.gov (United States)

    Liu, Cheng; Liao, Yingmin; Huang, Xiaojia

    2017-11-17

    This work prepared a new poly (ionic liquid)-functionalized magnetic adsorbent (PFMA) for the extraction of triazole fungicides (TFs) in environmental waters prior to determination by high performance liquid chromatography/diode array detection (HPLC-DAD). A polymerizable ionic liquid, 1-methyl-3-allylimidazolium bis(trifluoromethylsulfonyl)imide was employed to copolymerize with divinylbenzene on the surface of modified magnetite to fabricate the PFMA. The morphology, spectroscopic and magnetic properties of the new adsorbent were investigated by different techniques. A series of key parameters that influence the extraction performance including the amount of PFMA, desorption solvent, adsorption and desorption time, sample pH value and ionic strength were optimized in detail. Under the optimum conditions, the prepared PFMA could extract targeted TFs effectively and quickly under the format of magnetic solid-phase extraction (MSPE). Satisfactory linearities were achieved in the range of 0.1-200.0μg/L for triadimenol and 0.05-200.0μg/L for other TFs with good coefficients of determination above 0.99 for all analytes. The limits of detection (S/N=3) and limits of quantification (S/N=10) for TFs were in the range of 0.0050-0.0078μg/L and 0.017-0.026μg/L, respectively. Environmental waters including lake, river and well waters were used to demonstrate the applicability of developed MSPE-HPLC-DAD method, and satisfactory recoveries and repeatability were obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism.

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    Han Chow Chua

    Full Text Available Extracts of the pepper plant kava (Piper methysticum are effective in alleviating anxiety in clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s of the pharmacologically active constituents, kavalactones have not been established. γ-Aminobutyric acid type A receptors (GABAARs are assumed to be the in vivo molecular target of kavalactones based on data from binding assays, but evidence in support of a direct interaction between kavalactones and GABAARs is scarce and equivocal. In this study, we characterised the functional properties of the major anxiolytic kavalactone, kavain at human recombinant α1β2, β2γ2L, αxβ2γ2L (x = 1, 2, 3 and 5, α1βxγ2L (x = 1, 2 and 3 and α4β2δ GABAARs expressed in Xenopus oocytes using the two-electrode voltage clamp technique. We found that kavain positively modulated all receptors regardless of the subunit composition, but the degree of enhancement was greater at α4β2δ than at α1β2γ2L GABAARs. The modulatory effect of kavain was unaffected by flumazenil, indicating that kavain did not enhance GABAARs via the classical benzodiazepine binding site. The β3N265M point mutation which has been previously shown to profoundly decrease anaesthetic sensitivity, also diminished kavain-mediated potentiation. To our knowledge, this study is the first report of the functional characteristics of a single kavalactone at distinct GABAAR subtypes, and presents the first experimental evidence in support of a direct interaction between a kavalactone and GABAARs.

  4. Aronia melanocarpa (chokeberry) polyphenol-rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice.

    Science.gov (United States)

    Kim, Bohkyung; Ku, Chai Siah; Pham, Tho X; Park, Youngki; Martin, Derek A; Xie, Liyang; Taheri, Rod; Lee, Jiyoung; Bolling, Bradley W

    2013-05-01

    We hypothesized that a polyphenol-rich chokeberry extract (CBE) would modulate hepatic lipid metabolism and improve antioxidant function in apolipoprotein E knockout (apoE(-/-)) mice. ApoE(-/-) mice were fed diets containing 15% fat with 0.2% cholesterol alone or supplemented with 0.005% or 0.05% CBE for 4 weeks. CBE polyphenol content was determined by the total phenols, 4-dimethylaminocinnamaldehyde, and ultra high-performance liquid chromatography-mass spectrometry methods. The 0.05% CBE diet provided mice with mean daily doses of 1.2 mg gallic acid equivalents of total phenols, 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins (as catechin-equivalents), and 0.02 mg flavonols. The 0.05% CBE group had 12% less plasma total cholesterol concentrations than the control. Despite the hypocholesterolemic effect of CBE, hepatic mRNA levels of low-density lipoprotein receptor, hydroxyl-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase in CBE-fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipid content or the hepatic expression of genes involved in lipogenesis and fatty acid β-oxidation such as fatty acid synthase, carnitine palmitoyltransferase 1 and acyl-CoA oxidase. Plasma paraoxonase and catalase activities were significantly increased in mice fed 0.05% CBE. Both CBE diets increased hepatic glutathione peroxidase (GPx) activity but the 0.05% CBE group had 24% less proximal intestine GPx activity relative to controls. Thus, dietary CBE lowered total cholesterol and improved plasma and hepatic antioxidant function at nutritionally-relevant doses in apoE(-/-) mice. Furthermore, the CBE cholesterol-lowering mechanism in apoE(-/-) mice was independent of hepatic expression of genes involved in cholesterol metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage

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    Fu-Chao Liu

    2012-10-01

    Full Text Available ABSTRACT:Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients inshock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK/ hemeoxygenase-1 (HO-1 pathway, activates estrogen receptor (ER, and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.

  6. Effect of Semecarpus anacardium Linn. nut milk extract on rat neutrophil functions in adjuvant arthritis.

    Science.gov (United States)

    Ramprasath, V R; Shanthi, P; Sachdanandam, P

    2006-01-01

    Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA) and various inflammatory conditions, by accumulation and liberation of active proteolytic enzymes. The effect of milk extract of Semecarpus anacardium Linn. nuts (SA) at a dosage of 150 mg kg(-1) body weight day(-1) for 14 days on adjuvant arthritis was studied to gain some insight into this intriguing disease in relation to neutrophil functions. The decreased phagocytic function of neutrophils (phagocytic index and avidity index) found in adjuvant arthritis was significantly increased by the administration of the drug SA. Increased levels of reactive oxygen species (superoxide radical, hydroxyl radical, H2O2 and myeloperoxidase), lysosomal enzymes (acid phosphatase and cathepsin D) and increased accumulation of neutrophils in the joints observed in adjuvant arthritic animals were reverted back to near normal levels by treatment with SA. The results of this study indicate that SA can be considered to be a good therapeutic agent for inflammation and arthritis.

  7. Evaluation of endoscopic vein extraction on structural and functional viability of saphenous vein endothelium.

    Science.gov (United States)

    Hussaini, Bader E; Lu, Xiu-Gui; Wolfe, J Alan; Thatte, Hemant S

    2011-06-10

    Endothelial injury during harvest influences graft patency post CABG. We have previously shown that endoscopic harvest causes structural and functional damage to the saphenous vein (SV) endothelium. However, causes of such injury may depend on the extraction technique. In order to assess this supposition, we evaluated the effect of VirtuoSaph endoscopic SV harvesting technique (VsEVH) on structural and functional viability of SV endothelium using multiphoton imaging, biochemical and immunofluorescence assays. Nineteen patients scheduled for CABG were prospectively identified. Each underwent VsEVH for one portion and "No-touch" open SV harvesting (OSVH) for another portion of the SV. A two cm segment from each portion was immersed in GALA conduit preservation solution and transported overnight to our lab for processing. The segments were labeled with fluorescent markers to quantify cell viability, calcium mobilization and generation of nitric oxide. Morphology, expression, localization and stability of endothelial caveolin, eNOS, von Willebrand factor and cadherin were evaluated using immunofluorescence, Western blot and multiphoton microscopy (MPM). Morphological, biochemical and immunofluorescence parameters of viability, structure and function were well preserved in VsEVH group as in OSVH group. However, tonic eNOS activity, agonist-dependent calcium mobilization and nitric oxide production were partially attenuated in the VsEVH group. This study indicates that VirtuoSaph endoscopic SV harvesting technique preserves the structural and functional viability of SV endothelium, but may differentially attenuate the vasomotor function of the saphenous vein graft.

  8. Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway.

    Science.gov (United States)

    Song, Pingping; Trajkovic, Katarina; Tsunemi, Taiji; Krainc, Dimitri

    2016-02-24

    Mutations in PARK2 (parkin), which encodes Parkin protein, an E3 ubiquitin ligase, are associated with autosomal recessive early-onset Parkinson's disease (PD). While several studies implicated Parkin in the regulation of mitophagy and proteasomal degradation, the precise mechanism leading to neurodegeneration upon Parkin loss of function remains incompletely understood. In this study, we found that Parkin modulates the endocytic pathway through the regulation of endosomal structure and function. We showed that loss of Parkin function led to decreased endosomal tubulation and membrane association of vesicle protein sorting 35 (VPS35) and sorting nexin 1 (SNX1), as well as decreased mannose 6 phosphate receptor (M6PR), suggesting the impairment of retromer pathway in Parkin-deficient cells. We also found increased formation of intraluminal vesicles coupled with enhanced release of exosomes in the presence of mutant Parkin. To elucidate the molecular mechanism of these alterations in the endocytic pathway in Parkin-deficient cells, we found that Parkin regulates the levels and activity of Rab7 by promoting its ubiquitination on lysine 38 residue. Both endogenous Rab7 in Parkin-deficient cells and overexpressed K38 R-Rab7 mutant displayed decreased effector binding and membrane association. Furthermore, overexpression of K38R-Rab7 in HEK293 cells phenocopied the increased secretion of exosomes observed in Parkin-deficient cells, suggesting that Rab7 deregulation may be at least partially responsible for the endocytic phenotype observed in Parkin-deficient cells. These findings establish a role for Parkin in regulating the endo-lysosomal pathway and retromer function and raise the possibility that alterations in these pathways contribute to the development of pathology in Parkin-linked Parkinson's disease. Copyright © 2016 the authors 0270-6474/16/362425-13$15.00/0.

  9. Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.

    Science.gov (United States)

    Lee, Soo Vin; Choi, Kyung Ha; Choi, Young Whan; Hong, Jin Woo; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-04-01

    Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral

  10. [The modulating effect of the horn extract from the saiga of different age on the organothypic lymphoid tissue culture].

    Science.gov (United States)

    Chalisova, N I; Romanov, O E; Morozova, P Iu; Balykina, N A; Lesniak, V V; Sukhonos, Iu A; Zhekalov, A N

    2009-01-01

    The horn extracts from the saiga of different age were used to investigate its effect on organotypic tissue culture of explants from the rat spleen. From 4 to 10 amino acids were detected in the different extract fractions. The horn extracts from the young saiga, at the effective concentration 1 ng/ml, showed stimulating effect in spleen tissue cultures as compared to the control explants. No effect of extracts from the old saiga was observed in tissue culture. Possibly, a stimulation of the cellular proliferation is due to the great amino acid content in saiga horn; however this phenomenon is decreased by the aging.

  11. Modulating functions-based method for parameters and source estimation in one-dimensional partial differential equations

    KAUST Repository

    Asiri, Sharefa M.

    2016-10-20

    In this paper, modulating functions-based method is proposed for estimating space–time-dependent unknowns in one-dimensional partial differential equations. The proposed method simplifies the problem into a system of algebraic equations linear in unknown parameters. The well-posedness of the modulating functions-based solution is proved. The wave and the fifth-order KdV equations are used as examples to show the effectiveness of the proposed method in both noise-free and noisy cases.

  12. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

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    Anna Bauer-Mehren

    Full Text Available BACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and

  13. Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A.; Sanz, Ferran; Furlong, Laura I.

    2011-01-01

    Background Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. Principal Findings We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. Conclusions For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors

  14. Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions.

    Science.gov (United States)

    Pan, Qunwen; Liu, Hua; Zheng, Chunyan; Zhao, Yuhui; Liao, Xiaorong; Wang, Yan; Chen, Yanfang; Zhao, Bin; Lazartigues, Eric; Yang, Yi; Ma, Xiaotang

    2016-01-01

    Purpose: Microvesicles (MV) can modulate the function of recipient cells by transferring their contents. Our previous study highlighted that MV released from tumor necrosis factor-α (TNF-α) plus serum deprivation (SD)-stimulated endothelial progenitor cells, induce detrimental effects on endothelial cells. In this study, we investigated the potential effects of endothelial MV (EMV) on proliferation, migration, and apoptosis of human brain vascular smooth cells (HBVSMC). Methods: EMV were prepared from human brain microvascular endothelial cells (HBMEC) cultured in a TNF-α plus SD medium. RNase-EMV were made by treating EMV with RNase A for RNA depletion. The proliferation, apoptosis and migration abilities of HBVSMC were determined after co-culture with EMV or RNase-EMV. The Mek1/2 inhibitor, PD0325901, was used for pathway analysis. Western blot was used for analyzing the proteins of Mek1/2, Erk1/2, phosphorylation Erk1/2, activated caspase-3 and Bcl-2. The level of miR-146a-5p was measured by qRT-PCR. Results: (1) EMV significantly promoted the proliferation and migration of HBVSMC. The effects were accompanied by an increase in Mek1/2 and p-Erk1/2, which could be abolished by PD0325901; (2) EMV decreased the apoptotic rate of HBVSMC by approximately 35%, which was accompanied by cleaved caspase-3 down-regulation and Bcl-2 up-regulation; (3) EMV increased miR-146a-5p level in HBVSMC by about 2-folds; (4) RNase-treated EMV were less effective than EMV on HBVSMC activities and miR-146a-5p expression. Conclusion: EMV generated under inflammation challenge can modulate HBVSMC function and fate via their carried RNA. This is associated with activation of theMek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation, during which miR-146a-5p may play an important role. The data suggest that EMV derived from inflammation-challenged endothelial cells are detrimental to HBVSMC homeostatic functions, highlighting potential novel therapeutic targets for vascular diseases.

  15. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-07-02

    The maintenance of extracellular Na{sup +} and Cl{sup -} concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na{sup +} and Cl{sup -} reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg{sup -1}·day{sup -1}, sc) and progesterone (OVP, 1.7 mg·kg{sup -1}·day{sup -1}, sc). We assessed Na{sup +} and Cl{sup -} fractional excretion (FE{sub Na{sup {sub +}}} and FE{sub Cl{sup {sub -}}}, respectively) and renal and plasma catecholamine release concentrations. FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen

  16. Modulating epigenetic mechanisms: the diverse functions of Ski during cortical development.

    Science.gov (United States)

    Baranek, Constanze; Atanasoski, Suzana

    2012-07-01

    In the developing forebrain, neural stem and progenitor cells generate a large variety of neurons with specific functions in the mature cortex. A central issue is to understand the roles of transcriptional networks and regulatory pathways that control these complex developmental processes. The proto-oncogene Ski is a transcriptional regulator linked to the human 1p36 deletion syndrome, which involves a set of phenotypes including nervous system defects. Ski shows a dynamic expression pattern during cortical development and, accordingly, the phenotype of Ski-deficient cortices is complex, involving altered cell cycle characteristics of neural progenitors, disturbed timing of neurogenesis and mis-specification of projection neurons. Ski is likely to play a role in various pathways by virtue of its ability to interact with a range of signaling molecules, thereby modulating transcriptional activity of corresponding target genes. Ski regulates proliferation and differentiation of various cell types, and more recent data from my laboratory demonstrates that Ski is also involved in the specification of cortical projection neurons. This Point-of-View elucidates the role of Ski as an essential linker between sequence-specific transcription factors and non-DNA binding cofactors with chromatin modifying activities. In particular, it puts forward the hypothesis that the diverse functions of Ski as a co-repressor might be related to its association with distinct HDAC-complexes.

  17. Mast Cell Subsets and Their Functional Modulation by the Acanthocheilonema viteae Product ES-62

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    Dimity H. Ball

    2013-01-01

    Full Text Available ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of FcεRI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune diseases, mast cells are important in fighting infection, wound healing, and resolving inflammation, reflecting that mast cells exhibit a phenotypic and functional plasticity. We have therefore characterised the differential functional responses to antigen (via FcεRI and LPS and their modulation by ES-62 of the mature peritoneal-derived mast cells (PDMC; serosal and those of the connective tissue-like mast cells (CTMC and the mucosal-like mast cells derived from bone marrow progenitors (BMMC as a first step to produce disease tissue-targeted therapeutics based on ES-62 action. All three mast cell populations were rendered hyporesponsive by ES-62 and whilst the mechanisms underlying such desensitisation have not been fully delineated, they reflect a downregulation of calcium and PKCα signalling. ES-62 also downregulated MyD88 and PKCδ in mucosal-type BMMC but not PDMC, the additional signals targeted in mucosal-type BMMC likely reflecting that these cells respond to antigen and LPS by degranulation and cytokine secretion whereas PDMC predominantly respond in a degranulation-based manner.

  18. Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

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    Barja-Fidalgo C.

    2005-01-01

    Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

  19. Honey Bee Allatostatins Target Galanin/Somatostatin-Like Receptors and Modulate Learning: A Conserved Function?

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    Elodie Urlacher

    Full Text Available Sequencing of the honeybee genome revealed many neuropeptides and putative neuropeptide receptors, yet functional characterization of these peptidic systems is scarce. In this study, we focus on allatostatins, which were first identified as inhibitors of juvenile hormone synthesis, but whose role in the adult honey bee (Apis mellifera brain remains to be determined. We characterize the bee allatostatin system, represented by two families: allatostatin A (Apime-ASTA and its receptor (Apime-ASTA-R; and C-type allatostatins (Apime-ASTC and Apime-ASTCC and their common receptor (Apime-ASTC-R. Apime-ASTA-R and Apime-ASTC-R are the receptors in bees most closely related to vertebrate galanin and somatostatin receptors, respectively. We examine the functional properties of the two honeybee receptors and show that they are transcriptionally expressed in the adult brain, including in brain centers known to be important for learning and memory processes. Thus we investigated the effects of exogenously applied allatostatins on appetitive olfactory learning in the bee. Our results show that allatostatins modulate learning in this insect, and provide important insights into the evolution of somatostatin/allatostatin signaling.

  20. Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

    Science.gov (United States)

    Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

    2017-09-01

    In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

  1. Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging.

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    Martin Ulrich

    Full Text Available Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area. Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes.

  2. The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions.

    Science.gov (United States)

    Won, Jung Hee; Park, Jung Sik; Ju, Hyun Hee; Kim, Soyeon; Suh-Kim, Haeyoung; Ghil, Sung Ho

    2008-05-01

    Heterotrimeric GTP-binding proteins (G proteins) mediate signal transduction generated by neurotransmitters and hormones. Go, a member of the Go/Gi family, is the most abundant heterotrimeric G protein in the brain. Most mechanistic analyses on Go activation demonstrate that its action is mediated by the Gbetagamma dimer; downstream effectors for its alpha subunit (Goalpha) have not been clearly defined. Here, we employ the yeast two-hybrid system to screen for Goalpha-interacting partners in a cDNA library from human fetal brain. The transcription factor promyelocytic leukemia zinc finger protein (PLZF) specifically bound to Goalpha. Interactions between PLZF and Goalpha were confirmed using in vitro and in vivo affinity binding assays. Activated Goalpha interacted directly with PLZF, and enhanced its function as a transcriptional and cell growth suppressor. Notably, PLZF activity was additionally promoted by the Go/ialpha-coupled cannabinoid receptor (CB) in HL60 cells endogenously expressing CB and PLZF. These results collectively suggest that Goalpha modulates the function of PLZF via direct interactions. Our novel findings provide insights into the diverse cellular roles of Goalpha and its coupled receptor.

  3. Dipole induced conductance modulation in chromophore-functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Zhao, Yuanchun; Huang, Changshui; Kim, Myungwoong; Gopalan, Padma; Eriksson, Mark

    2013-03-01

    Single-walled carbon nanotubes (SWNTs) are highly sensitive to local electrostatic environments, making SWNT field-effect transistors (FETs) of interest for a number of sensor applications and optoelectronic devices. Here we demonstrate a direct correlation between the conduction of SWNTs and their surrounding dipolar environments. We use azobenzene-based dipolar chromophores, Disperse Red 1 (DR1) and its derivatives to functionalize the sidewalls of SWNTs. The chromophores are coupled with a pyrenebutyric group for realizing noncovalent attachment and to attempt to direct their dipole moments. The functionalizing chromophores produce a dipole field that shifts the threshold voltage (Vth) of the nanotube FET. Under light illumination, these molecules isomerize from the ground trans state to the excited cis state, leading to a decrease of their dipole moments. This dipole moment change acts as an additional gate, causing a shift in Vth. Our results provide a new insight into the photogating mechanisms of the nanotube-chromophore hybrid devices, and they reveal the possibility to modulate optoelectronic properties of nanotube-hybrid devices by designing chromophores with required photosensitive features.

  4. Modulation of working memory function by motivation through loss-aversion.

    Science.gov (United States)

    Krawczyk, Daniel C; D'Esposito, Mark

    2013-04-01

    Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Copyright © 2011 Wiley Periodicals, Inc.

  5. Holographic Fabrication of Designed Functional Defect Lines in Photonic Crystal Lattice Using a Spatial Light Modulator

    Directory of Open Access Journals (Sweden)

    Jeffrey Lutkenhaus

    2016-04-01

    Full Text Available We report the holographic fabrication of designed defect lines in photonic crystal lattices through phase engineering using a spatial light modulator (SLM. The diffracted beams from the SLM not only carry the defect’s content but also the defect related phase-shifting information. The phase-shifting induced lattice shifting in photonic lattices around the defects in three-beam interference is less than the one produced by five-beam interference due to the alternating shifting in lattice in three beam interference. By designing the defect line at a 45 degree orientation and using three-beam interference, the defect orientation can be aligned with the background photonic lattice, and the shifting is only in one side of the defect line, in agreement with the theory. Finally, a new design for the integration of functional defect lines in a background phase pattern reduces the relative phase shift of the defect and utilizes the different diffraction efficiency between the defect line and background phase pattern. We demonstrate that the desired and functional defect lattice can be registered into the background lattice through the direct imaging of designed phase patterns.

  6. Subthalamic nucleus stimulation and levodopa modulate cardiovascular autonomic function in Parkinson's disease.

    Science.gov (United States)

    Li, Kai; Haase, Rocco; Rüdiger, Heinz; Reimann, Manja; Reichmann, Heinz; Wolz, Martin; Ziemssen, Tjalf

    2017-08-01

    We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six Parkinson's disease patients with bilateral subthalamic nucleus stimulation in a stable state were tested under stimulation off and dopaminergic medication off (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and stimulation on and medication (levodopa) on (ON-ON) conditions by recording continuously blood pressure, ECG, and respiration at rest, during metronomic deep breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses were performed by trigonometric regressive spectral analysis. Subthalamic nucleus stimulation and levodopa had multiple influences. (1) Systolic blood pressure during tilt-up was reduced by subthalamic nucleus stimulation, and then further by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different effects on sympathetic and parasympathetic regulations in Parkinson's disease. (3) Levodopa decreased baroreflex sensitivity and RR interval only in the orthostatic hypotension group, and had opposite effects on the non-orthostatic hypotension group. These findings indicate that subthalamic nucleus stimulation and levodopa have different effects on cardiovascular autonomic function in Parkinson's disease, which are modulated by the presence of orthostatic hypotension as well.

  7. The extracellular matrix modulates fibroblast phenotype and function in the infarcted myocardium

    Science.gov (United States)

    Dobaczewski, Marcin; de Haan, Judith J; Frangogiannis, Nikolaos G

    2012-01-01

    Cardiac fibroblasts are key cellular effectors of cardiac repair; their phenotype and function are modulated by interactions with extracellular matrix proteins. This review manuscript discusses the effects of the extracellular matrix on the inflammatory and reparative properties of fibroblasts in the infarcted myocardium. Early generation of matrix fragments in the infarct induces a pro-inflammatory and matrix-degrading fibroblast phenotype. Formation of a fibrin/fibronectin-rich provisional matrix serves as a conduit for migration of fibroblasts into the infarcted area. Induction of ED-A fibronectin and non-fibrillar collagens may contribute to myofibroblast transdifferentiation. Upregulation of matricellular proteins promotes transduction of growth factor and cytokine-mediated signals. As the scar matures, matrix cross-linking, clearance of matricellular proteins and reduced growth factor signaling cause deactivation and apoptosis of reparative infarct fibroblasts. Understanding the effects of matrix components on infarct fibroblasts may guide the design of peptides that reproduce, or inhibit, specific matricellular functions, attenuating adverse remodeling. PMID:22956156

  8. Modulation of Gut Microbiome Composition and Function in Experimental Colitis Treated with Sulfasalazine.

    Science.gov (United States)

    Zheng, Haihui; Chen, Mingyi; Li, Yuan; Wang, Yuanyuan; Wei, Lin; Liao, Ziqiong; Wang, Mengxia; Ma, Fangli; Liao, Qiongfeng; Xie, Zhiyong

    2017-01-01

    Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.

  9. Protein function prediction using text-based features extracted from the biomedical literature: the CAFA challenge.

    Science.gov (United States)

    Wong, Andrew; Shatkay, Hagit

    2013-01-01

    Advances in sequencing technology over the past decade have resulted in an abundance of sequenced proteins whose function is yet unknown. As such, computational systems that can automatically predict and annotate protein function are in demand. Most computational systems use features derived from protein sequence or protein structure to predict function. In an earlier work, we demonstrated the utility of biomedical literature as a source of text features for predicting protein subcellular location. We have also shown that the combination of text-based and sequence-based prediction improves the performance of location predictors. Following up on this work, for the Critical Assessment of Function Annotations (CAFA) Challenge, we developed a text-based system that aims to predict molecular function and biological process (using Gene Ontology terms) for unannotated proteins. In this paper, we present the preliminary work and evaluation that we performed for our system, as part of the CAFA challenge. We have developed a preliminary system that represents proteins using text-based features and predicts protein function using a k-nearest neighbour classifier (Text-KNN). We selected text features for our classifier by extracting key terms from biomedical abstracts based on their statistical properties. The system was trained and tested using 5-fold cross-validation over a dataset of 36,536 proteins. System performance was measured using the standard measures of precision, recall, F-measure and overall accuracy. The performance of our system was compared to two baseline classifiers: one that assigns function based solely on the prior distribution of protein function (Base-Prior) and one that assigns function based on sequence similarity (Base-Seq). The overall prediction accuracy of Text-KNN, Base-Prior, and Base-Seq for molecular function classes are 62%, 43%, and 58% while the overall accuracy for biological process classes are 17%, 11%, and 28% respectively. Results

  10. Protein Function Prediction using Text-based Features extracted from the Biomedical Literature: The CAFA Challenge

    Science.gov (United States)

    2013-01-01

    Background Advances in sequencing technology over the past decade have resulted in an abundance of sequenced proteins whose function is yet unknown. As such, computational systems that can automatically predict and annotate protein function are in demand. Most computational systems use features derived from protein sequence or protein structure to predict function. In an earlier work, we demonstrated the utility of biomedical literature as a source of text features for predicting protein subcellular location. We have also shown that the combination of text-based and sequence-based prediction improves the performance of location predictors. Following up on this work, for the Critical Assessment of Function Annotations (CAFA) Challenge, we developed a text-based system that aims to predict molecular function and biological process (using Gene Ontology terms) for unannotated proteins. In this paper, we present the preliminary work and evaluation that we performed for our system, as part of the CAFA challenge. Results We have developed a preliminary system that represents proteins using text-based features and predicts protein function using a k-nearest neighbour classifier (Text-KNN). We selected text features for our classifier by extracting key terms from biomedical abstracts based on their statistical properties. The system was trained and tested using 5-fold cross-validation over a dataset of 36,536 proteins. System performance was measured using the standard measures of precision, recall, F-measure and overall accuracy. The performance of our system was compared to two baseline classifiers: one that assigns function based solely on the prior distribution of protein function (Base-Prior) and one that assigns function based on sequence similarity (Base-Seq). The overall prediction accuracy of Text-KNN, Base-Prior, and Base-Seq for molecular function classes are 62%, 43%, and 58% while the overall accuracy for biological process classes are 17%, 11%, and 28

  11. Modulated modularity clustering as an exploratory tool for functional genomic inference.

    Directory of Open Access Journals (Sweden)

    Eric A Stone

    2009-05-01

    Full Text Available In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC, seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation.

  12. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  13. Role of architecture in the function and specificity of two Notch-regulated transcriptional enhancer modules.

    Science.gov (United States)

    Liu, Feng; Posakony, James W

    2012-07-01

    In Drosophila melanogaster, cis-regulatory modules that are activated by the Notch cell-cell signaling pathway all contain two types of transcription factor binding sites: those for the pathway's transducing factor Suppressor of Hairless [Su(H)] and those for one or more tissue- or cell type-specific factors called "local activators." The use of different "Su(H) plus local activator" motif combinations, or codes, is critical to ensure that only the correct subset of the broadly utilized Notch pathway's target genes are activated in each developmental context. However, much less is known about the role of enhancer "architecture"--the number, order, spacing, and orientation of its component transcription factor binding motifs--in determining the module's specificity. Here we investigate the relationship between architecture and function for two Notch-regulated enhancers with spatially distinct activities, each of which includes five high-affinity Su(H) sites. We find that the first, which is active specifically in the socket cells of external sensory organs, is largely resistant to perturbations of its architecture. By contrast, the second enhancer, active in the "non-SOP" cells of the proneural clusters from which neural precursors arise, is sensitive to even simple rearrangements of its transcription factor binding sites, responding with both loss of normal specificity and striking ectopic activity. Thus, diverse cryptic specificities can be inherent in an enhancer's particular combination of transcription factor binding motifs. We propose that for certain types of enhancer, architecture plays an essential role in determining specificity, not only by permitting factor-factor synergies necessary to generate the desired activity, but also by preventing other activator synergies that would otherwise lead to unwanted specificities.

  14. Hexane extract of Raphanus sativus L. roots inhibits cell proliferation and induces apoptosis in human cancer cells by modulating genes related to apoptotic pathway.

    Science.gov (United States)

    Beevi, Syed Sultan; Mangamoori, Lakshmi Narasu; Subathra, Murugan; Edula, Jyotheeswara Reddy

    2010-09-01

    Raphanus sativus, a common cruciferous vegetable has been attributed to possess a number of pharmacological and therapeutic properties. It has been used in indigenous system of medicine for the treatment of various human ailments in India. This present study evaluated the chemopreventive efficacy of different parts of R. sativus such as root, stem and leaves, extracted with solvents of varying polarity and investigated the molecular mechanism leading to growth arrest and apoptotic cell death in human cancer cell lines. Of the different parts, significant growth inhibitory effect was observed with hexane extract of R. sativus root. Analysis of hexane extract by GC-MS revealed the presence of several isothiocyanates (ITCs) such as 4-(methylthio)-3-butenyl isothiocyanate (MTBITC), 4-(methylthio)-3-butyl isothiocyanate (erucin), 4-methylpentyl isothiocyanate, 4-pentenyl isothiocyanate and sulforaphene. R. sativus root extract induced cell death both in p53 proficient and p53 deficient cell lines through induction of apoptotic signaling pathway regardless of the p53 status of cells. The molecular mechanisms underlying R. sativus-induced apoptosis may involve interactions among Bcl(2) family genes, as evidenced by up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes along with activation of Caspase-3. Our findings present the first evidence that hexane extract of R. sativus root exerts potential chemopreventive efficacy and induces apoptosis in cancer cell lines through modulation of genes involved in apoptotic signaling pathway.

  15. Modulation of rat and human cytochromes P450 involved in PhIP and 4-ABP activation by an aqueous extract of Phyllanthus orbicularis.

    Science.gov (United States)

    Ferrer, Mirle; Cristófol, Carles; Sánchez-Lamar, Angel; Fuentes, Jorge Luís; Barbé, Jordi; Llagostera, Montserrat

    2004-02-01

    Phyllanthus orbicularis HBK (Euphorbiaceae) is a medicinal plant, endemic to Cuba, whose aqueous extract has proven antimutagenic effects against hydrogen peroxide and some promutagenic aromatic amines (AAs), in addition to its antiviral properties. In this paper, antimutagenesis of this extract against two carcinogenic AAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 4-aminobiphenyl (4-ABP) has been studied. Liver microsomal fractions from both induced rats and humans were used to metabolise both procarcinogenic compounds in the Salmonella assay. The plant extract was effective in reducing the mutagenesis of these AAs, activated by both kinds of fractions. The optimal antimutagenic effect was obtained when both AAs were metabolised by human enzymes, with an almost total reduction of 4-ABP mutagenesis and a decrease of about 75% of PhIP mutagenicity. Mutagenicity of both AAs, activated by induced rat fraction, was only decreased by about 50%. Inhibition by plant extract of alkoxyresorufin O-dealkylation activities, dependent on CYP1A, of both fractions was determined. In accordance with the results obtained, the inhibition or modulation of CYP1A subfamily activities, and possibly of CYP1A2, is thought to be the main mechanism of antimutagenesis of the aqueous extract of Phyllanthus orbicularis against 4-ABP and PhIP.

  16. The use of 90% Aloe vera freeze drying as the modulator of collagen density in extraction socket of incicivus Cavia cobaya

    Directory of Open Access Journals (Sweden)

    Ester Arijani

    2008-06-01

    Full Text Available Wound healing is basically a complex process in which cellular and matrix act in concern to re-establish the integrity of injury tissues. This process can be simplified to be healing process consisted of haemostatic, inflammation, cell proliferation and tissue remodeling. The aimed of this research was to know the influence of freeze drying 90% Aloe vera application as mandible collagen density modulator in extraction socket of incisive Cavia cobaya. This research was done using Post Test Only Control Groups Design and Cavia cobaya as the sample. Six samples of each control group and 90% Aloe vera group applied to test each collagen density for three days and seven days. Then, the data was analyzed statistically using Mann Whitney with 5% significance rate. The result of the study indicates that administering 90% Aloe vera can accelerate the growth of collagen density in healing process of extraction socket. The conclusion is 90% Aloe vera can modulate the density of collageneous fiber in socket of extraction incicivus tooth wound of Cavia cobaya.

  17. MAE-FMD: multi-agent evolutionary method for functional module detection in protein-protein interaction networks.

    Science.gov (United States)

    Ji, Jun Zhong; Jiao, Lang; Yang, Cui Cui; Lv, Jia Wei; Zhang, Ai Dong

    2014-09-30

    Studies of functional modules in a Protein-Protein Interaction (PPI) network contribute greatly to the understanding of biological mechanisms. With the development of computing science, computational approaches have played an important role in detecting functional modules. We present a new approach using multi-agent evolution for detection of functional modules in PPI networks. The proposed approach consists of two stages: the solution construction for agents in a population and the evolutionary process of computational agents in a lattice environment, where each agent corresponds to a candidate solution to the detection problem of functional modules in a PPI network. First, the approach utilizes a connection-based encoding scheme to model an agent, and employs a random-walk behavior merged topological characteristics with functional information to construct a solution. Next, it applies several evolutionary operators, i.e., competition, crossover, and mutation, to realize information exchange among agents as well as solution evolution. Systematic experiments have been conducted on three benchmark testing sets of yeast networks. Experimental results show that the approach is more effective compared to several other existing algorithms. The algorithm has the characteristics of outstanding recall, F-measure, sensitivity and accuracy while keeping other competitive performances, so it can be applied to the biological study which requires high accuracy.

  18. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling.

    Science.gov (United States)

    Wang, Kai; Jin, Xiaolu; Chen, Yifan; Song, Zehe; Jiang, Xiasen; Hu, Fuliang; Conlon, Michael A; Topping, David L

    2016-05-07

    Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.

  19. Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

    LENUS (Irish Health Repository)

    Condron, Claire

    2010-08-01

    Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

  20. Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions.

    Science.gov (United States)

    Loers, Gabriele; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Chaudhury, Sidhartha; Wallqvist, Anders; Kaur, Gurcharan; Schachner, Melitta

    2016-01-01

    Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 α2,8-linked sialic acid residues, modulates development of the nervous system by enhancing cell migration, axon pathfinding, and synaptic targeting and by regulating differentiation of progenitor cells. PSA also functions in developing and adult immune systems and is a signature of many cancers. In this study we identified vinorelbine, a semi-synthetic third generation vinca alkaloid, and epirubicin, an anthracycline and 4'-epimer of doxorubicin, as PSA mimetics. Similar to PSA, vinorelbine and epirubicin bind to the PSA-specific monoclonal antibody 735 and compete with the bacterial analog of PSA, colominic acid in binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite outgrowth of cerebellar neurons via the neural cell adhesion molecule, via myristoylated alanine-rich C kinase substrate, and via fibroblast growth factor receptor, signaling through Erk pathways. Furthermore, the two compounds enhance process formation of Schwann cells and migration of cerebellar neurons in culture, and reduce migration of astrocytes after injury. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds vinorelbine and epirubicin, thus raising the possibility to re-target drugs used in treatment of cancers to nervous system repair. Vinorelbine and epirubicin, identified as PSA mimetics, enhance, like PSA, neuronal migration, neuritogenesis, and formation of Schwann cell processes, and reduce astrocytic migration. Ablating NCAM, inhibiting fibroblast growth factor (FGFR) receptor, or adding the effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) minimize the vinorelbine and epirubicin effects, indicating that they are true PSA mimetics triggering PSA-mediated functions. © 2015 International Society for Neurochemistry.

  1. Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

    Directory of Open Access Journals (Sweden)

    Matthew eBecker

    2015-01-01

    Full Text Available In addition to the disruption of neural function below spinal cord injuries (SCI, there also can be changes in neuronal properties above and below the lesion site. The relevance of these changes is generally unclear, but they must be understood if we are to provide rational interventions. Pharmacological approaches to improving locomotor function have been studied extensively, but it is still unclear what constitutes an optimal approach. Here, we have used the lamprey to compare the modulatory effects of 5-HT and lesion-induced changes in cellular and synaptic properties in unlesioned and lesioned animals. While analyses typically focus on the sub-lesion spinal cord, we have also examined effects above the lesion to see if there are changes here that could potentially contribute to the functional recovery.Cellular and synaptic properties differed in unlesioned and lesioned spinal cords and above and below the lesion site. The cellular and synaptic modulatory effects of 5-HT also differed in lesioned and unlesioned animals, again in region-specific ways above and below the lesion site. A role for 5-HT in promoting recovery was suggested by the potential for improvement in locomotor activity when 5-HT was applied to poorly recovered animals, and by the consistent failure of animals to recover when they were incubated in PCPA to deplete 5-HT. However, PCPA did not affect swimming in animals that had already recovered, suggesting a difference in 5-HT effects after lesioning. These results show changes in 5-HT modulation and cellular and synaptic properties after recovery from a spinal cord transection. Importantly, effects are not confined to the sub-lesion spinal cord but also occur above the lesion site. This suggests that the changes may not simply reflect compensatory responses to the loss of descending inputs, but reflect the need for co-ordinated changes above and below the lesion site. The changes in modulatory effects should be considered in

  2. Chemical characteristic and functional properties of arenga starch-taro (Colocasia esculanta L.) flour noodle with turmeric extracts addition

    Science.gov (United States)

    Ervika Rahayu N., H.; Ariani, Dini; Miftakhussolikhah, E., Maharani P.; Yudi, P.

    2017-01-01

    Arenga starch-taro (Colocasia esculanta L.) flour noodle is an alternative carbohydrate source made from 75% arenga starch and 25% taro flour, but it has a different color with commercial noodle product. The addition of natural color from turmeric may change the consumer preference and affect chemical characteristic and functional properties of noodle. This research aims to identify chemical characteristic and functional properties of arenga starch-taro flour noodle with turmeric extract addition. Extraction was performed using 5 variances of turmeric rhizome (0.06; 0.12; 0.18; 0.24; and 0.30 g (fresh weight/ml water). Then, noodle was made and chemical characteristic (proximate analysis) as well as functional properties (amylose, resistant starch, dietary fiber, antioxidant activity) were then evaluated. The result showed that addition of turmeric extract did not change protein, fat, carbohydrate, amylose, and resistant starch content significantly, while antioxidant activity was increased (23,41%) with addition of turmeric extract.

  3. Functional milk beverage fortified with phenolic compounds extracted from olive vegetation water, and fermented with functional lactic acid bacteria.

    Science.gov (United States)

    Servili, M; Rizzello, C G; Taticchi, A; Esposto, S; Urbani, S; Mazzacane, F; Di Maio, I; Selvaggini, R; Gobbetti, M; Di Cagno, R

    2011-05-14

    Functional milk beverages (FMB100 and FMB200) fortified with phenolic compounds (100 and 200mg/l) extracted from olive vegetable water, and fermented with γ-amino butyric acid (GABA)-producing (Lactobacillus plantarum C48) and autochthonous human gastro-intestinal (Lactobacillus paracasei 15N) lactic acid bacteria were manufactured. A milk beverage (MB), without addition of phenolic compounds, was used as the control. Except for a longer latency phase of FMB200, the three beverages showed an almost similar kinetic of acidification, consumption of lactose and synthesis of lactic acid. Apart from the beverage, Lb. plantarum C48 showed a decrease of ca. Log 2.52-2.24 cfu/ml during storage. The cell density of functional Lb. paracasei 15N remained always above the value of Log 8.0 cfu/ml. During fermentation, the total concentration of free amino acids markedly increased without significant (P > 0.05) differences between beverages. The concentration of GABA increased during fermentation and further storage (63.0 ± 0.6-67.0 ± 2.1mg/l) without significant (P > 0.05) differences between beverages. After fermentation, FMB100 and FMB200 showed the same phenolic composition of the phenol extract from olive vegetable water but a different ratio between 3,4-DHPEA and 3,4-DHPEA-EDA. During storage, the concentrations of 3,4-DHPEA-EDA, p-HPEA and verbascoside of both FMB100 and FMB200 decreased. Only the concentration of 3,4-DHPEA increased. As shown by SPME-GC-MS analysis, diactetyl, acetoin and, especially, acetaldehyde were the main volatile compounds found. The concentration of phenolic compounds does not interfere with the volatile composition. Sensory analyses based on triangle and paired comparison tests showed that phenolic compounds at the concentrations of 100 or 200mg/l were suitable for addition to functional milk beverages. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. The Program Manager’s Support System (PMSS). An Executive Overview and Descriptions of Functional Modules

    Science.gov (United States)

    1989-05-01

    50 Program Office Organization and Staffing Module 50 Expert Systems for Acquisition Strategies 51 Procurement Document Generator Module 51...PC; Z-248 50 trade-off analysis Program Office Organization PROS Develop PMO organization Prototype IBM-PC; Z-248 50 and Staffing charts, on board...prototype moduie. It requires a color graphics card. Program Office Organization and Staffing (PROS) Module The Program Office Organization and Staffing

  5. Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings

    DEFF Research Database (Denmark)

    Bader, Benjamin M; Steder, Anne; Klein, Anders Bue

    2017-01-01

    The numerous γ-aminobutyric acid type A receptor (GABAAR) subtypes are differentially expressed and mediate distinct functions at neuronal level. In this study we have investigated GABAAR-mediated modulation of the spontaneous activity patterns of primary neuronal networks from murine frontal...

  6. Event-rate manipulation and its effect on arousal modulation and response inhibition in adults with high functioning autism

    NARCIS (Netherlands)

    Raymaekers, R; van der Meere, J; Roeyers, H

    The aim of the current study was to evaluate arousal modulation and response inhibition in adults with high functioning autism (HFA). Using a go/no-go paradigm with varying presentation rate, it was found that performance efficiency (Mean RT, Standard Deviation of RT and Errors of Commission) in

  7. Dry olive leaf extract (DOLE down-regulates the progression of experimental immune-mediated diabetes by modulation of cytokine profile in the draining lymph nodes

    Directory of Open Access Journals (Sweden)

    Saksida Tamara

    2011-01-01

    Full Text Available We have recently demonstrated the beneficial effects of dry olive leaf extract (DOLE in two preclinical models of type 1 diabetes. Here we analyze the potential mechanisms underlying diabetes amelioration at the level of lymph node drainage. Treatment of C57BL/6 mice with DOLE during induction of diabetes with multiple low doses of streptozotocin (MLD-SZ modulated cytokine expression and production in pancreatic lymph node cells, thereby changing the balance between potentially pathogenic and down-regulating cytokines. These results support the immunoregulatory potential of DOLE which takes place at the level of lymph node drainage and preserves the target tissue from autoimmune attack.

  8. Cross-Language Competition is Modulated by Individual Differences in Executive Function: An Aging Study

    Directory of Open Access Journals (Sweden)

    Aruna Sudarshan

    2014-04-01

    Full Text Available Background: Accumulating evidence from empirical and clinical studies has shown evidence suggesting that lexical selection is more difficult when there is greater cross-language competition. These studies further suggest that higher cognitive mechanisms, particularly inhibitory control, may play a crucial role in the regulation of languages in the bilingual brain. An important implication of this finding is that the process of lexical selection in a bilingual context may be particularly difficult for older adults for whom a vast body of literature has demonstrated a decline in cognitive functions required for language processing and production. However, benefits in executive functions (EF conferred by life-long bilingualism may protect against age-related difficulties in language skills (1. Here, we sought to investigate whether older adults resolved within- and cross-language lexical competition differently from younger adults and whether factors such as word status (cognate and non-cognate word processing and individual differences in domain-general executive control modulated cross-language interference resolution. Methods: In a picture-word interference paradigm, French-English bilingual younger and older adults named cognate and non-cognate pictures in English while ignoring within- and cross-language auditory distractor words (at varying SOAs. The distractors exhibited three different relations to the cognate target picture (Cactus: semantic (Thorn or Épine, phonological (Canvas or Cahier (notebook and unrelated control (Soap or Meuble (furniture. An additional target-distractor relation was included for the non-cognate target pictures: phonological relation to the translation (Gâteau of the target (Cake – (Garden or Garçon (boy. Additionally, to evaluate whether cross-language interference is modulated by individual differences in executive control, a battery of EF tests was administered. To further imply causality to EF and

  9. Effect of Roselle calyces extract on the chemical and sensory properties of functional cupcakes

    Directory of Open Access Journals (Sweden)

    A.R. Abdel-Moemin

    2016-12-01

    Full Text Available Roselle calyces (RC are a major crop for export and used to make a common drink in Egypt. Dried RC are commercially available and appreciated to obtain concentrated extracts which might be used in the food and pharmaceutical industries for color and heath benefits. The objective of this research was to determine the chemical and the sensory properties of cupcakes formulated with Roselle calyces extract (RCE. Proximate analysis, anthocyanins, ascorbic acid, titrable acidity, % retaining of anthocyanins, color and sensory evaluations were done. RC cupcakes had high sensory scores (P < 0.05 compared to control cupcakes. The parameter a* was significantly red in the RC cupcakes compared to control cupcakes along with 77% retaining of anthocyanins. The consumption of 100 g of the RC cupcakes would provide 465 mg/100 g dry matter anthocyanin that is more than 2 folds of the minimum average of the daily intake of anthocyanins for Americans, along ∼1/3 of the daily dietary fiber intake to achieve fiber adequacy according to the Scientific Advisory Committee on Nutrition. RC cupcake can be a functional food and would have a “clean” label with cost effective advantage.

  10. In vitro functional properties of crude extracts and isolated compounds from banana pseudostem and rhizome.

    Science.gov (United States)

    Kandasamy, Saravanan; Ramu, Sasikala; Aradhya, Somaradhya Mallikarjuna

    2016-03-15

    Pseudostem and rhizome are the significant bio-waste generated (43.48%) from the banana plant post fruit harvest, which are usually left in the plantation or incinerated and wasted. Amounts used in production for consumption are negligible. However, the material has an important part to play in indigenous systems of medicine. Based on the huge volume of bio-waste generated and its traditional medicinal use, it is worth exploiting it as a source of natural bioactive compounds. In the current study, sequential extracts from banana pseudostem (BPS) and rhizome (BR), and isolated compounds including chlorogenic acid, 4-epicyclomusalenone and cycloeucalenol acetate, were tested for their antimicrobial activity, antiplatelet aggregation and cytotoxicity. Isolated compounds and crude extracts exhibited strong antimicrobial activity against a wide range of bacterial and fungal strains, platelet aggregation induced by collagen and cytotoxicity towards human liver cancer (HepG2) cells. Banana plant bio-waste, pseudostem and rhizome may serve as a potential source of multifunctional bioactive compounds and functional ingredient in food and other allied industries. © 2015 Society of Chemical Industry.

  11. Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio.

    Science.gov (United States)

    Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

    2015-07-16

    In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data. Published by Elsevier Ltd.

  12. A Decentralized Wireless Solution to Monitor and Diagnose PV Solar Module Performance Based on Symmetrized-Shifted Gompertz Functions.

    Science.gov (United States)

    Molina-García, Angel; Campelo, José Carlos; Blanc, Sara; Serrano, Juan José; García-Sánchez, Tania; Bueso, María C

    2015-07-29

    This paper proposes and assesses an integrated solution to monitor and diagnose photovoltaic (PV) solar modules based on a decentralized wireless sensor acquisition system. Both DC electrical variables and environmental data are collected at PV module level using low-cost and high-energy efficiency node sensors. Data is real-time processed locally and compared with expected PV module performances obtained by a PV module model based on symmetrized-shifted Gompertz functions (as previously developed and assessed by the authors). Sensor nodes send data to a centralized sink-computing module using a multi-hop wireless sensor network architecture. Such integration thus provides extensive analysis of PV installations, and avoids off-line tests or post-processing processes. In comparison with previous approaches, this solution is enhanced with a low-cost system and non-critical performance constraints, and it is suitable for extensive deployment in PV power plants. Moreover, it is easily implemented in existing PV installations, since no additional wiring is required. The system has been implemented and assessed in a Spanish PV power plant connected to the grid. Results and estimations of PV module performances are also included in the paper.

  13. Abdicating power for control: a precision timing strategy to modulate function of flight power muscles

    Science.gov (United States)

    Sponberg, S.; Daniel, T. L.

    2012-01-01

    Muscles driving rhythmic locomotion typically show strong dependence of power on the timing or phase of activation. This is particularly true in insects' main flight muscles, canonical examples of muscles thought to have a dedicated power function. However, in the moth (Manduca sexta), these muscles normally activate at a phase where the instantaneous slope of the power–phase curve is steep and well below maximum power. We provide four lines of evidence demonstrating that, contrary to the current paradigm, the moth's nervous system establishes significant control authority in these muscles through precise timing modulation: (i) left–right pairs of flight muscles normally fire precisely, within 0.5–0.6 ms of each other; (ii) during a yawing optomotor response, left—right muscle timing differences shift throughout a wider 8 ms timing window, enabling at least a 50 per cent left–right power differential; (iii) timing differences correlate with turning torque; and (iv) the downstroke power muscles alone causally account for 47 per cent of turning torque. To establish (iv), we altered muscle activation during intact behaviour by stimulating individual muscle potentials to impose left—right timing differences. Because many organisms also have muscles operating with high power–phase gains (Δpower/Δphase), this motor control strategy may be ubiquitous in locomotor systems. PMID:22833272

  14. Abdicating power for control: a precision timing strategy to modulate function of flight power muscles.

    Science.gov (United States)

    Sponberg, S; Daniel, T L

    2012-10-07

    Muscles driving rhythmic locomotion typically show strong dependence of power on the timing or phase of activation. This is particularly true in insects' main flight muscles, canonical examples of muscles thought to have a dedicated power function. However, in the moth (Manduca sexta), these muscles normally activate at a phase where the instantaneous slope of the power-phase curve is steep and well below maximum power. We provide four lines of evidence demonstrating that, contrary to the current paradigm, the moth's nervous system establishes significant control authority in these muscles through precise timing modulation: (i) left-right pairs of flight muscles normally fire precisely, within 0.5-0.6 ms of each other; (ii) during a yawing optomotor response, left-right muscle timing differences shift throughout a wider 8 ms timing window, enabling at least a 50 per cent left-right power differential; (iii) timing differences correlate with turning torque; and (iv) the downstroke power muscles alone causally account for 47 per cent of turning torque. To establish (iv), we altered muscle activation during intact behaviour by stimulating individual muscle potentials to impose left-right timing differences. Because many organisms also have muscles operating with high power-phase gains (Δ(power)/Δ(phase)), this motor control strategy may be ubiquitous in locomotor systems.

  15. Functional toxicogenomic profiling expands insight into modulators of formaldehyde toxicity in yeast

    Directory of Open Access Journals (Sweden)

    Matthew North

    2016-11-01

    Full Text Available Formaldehyde (FA is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

  16. Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions.

    Science.gov (United States)

    Akakabe, Yoshiki; Koide, Masahiro; Kitamura, Youhei; Matsuo, Kiyonari; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Miyata, Keishi; Oike, Yuichi; Ikeda, Koji

    2013-01-01

    Insulin resistance is closely associated with obesity and is one of the earliest symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis. Here we show that Ecscr (endothelial cell surface expressed chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane protein that regulates endothelial cell signalling, is highly expressed in white and brown adipose tissues, and regulates energy metabolism and glucose homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a normal chow show improved glucose tolerance and enhanced insulin sensitivity. We demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial nitric oxide synthase activation in endothelial cells, which increases insulin delivery into the skeletal muscle. Ecscr deletion also protects mice on a high-fat diet from obesity and obesity-related metabolic disorders by enhancing adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in endothelial cells impairs glucose tolerance and predisposes mice to diet-induced obesity. Our results suggest that the inactivation of Ecscr enhances insulin sensitivity and may represent a new therapeutic strategy for treating metabolic syndrome.

  17. Epigenetic modulators of monocytic function: implication for steady state and disease in the CNS .

    Directory of Open Access Journals (Sweden)

    F. Nina Papavasiliou

    2016-01-01

    Full Text Available Epigenetic alterations are necessary for the establishment of functional and phenotypic diversity in populations of immune cells of the monocytic lineage. The epigenetic status of individual genes at different time points defines their transcriptional responses throughout development and in response to environmental stimuli. Epigenetic states are defined at the level of DNA modifications, chromatin modifications, as well as at the level of RNA base changes through RNA editing. Drawing from lessons regarding the epigenome and epitranscriptome of cells of the monocytic lineage in the periphery, and from recently published RNAseq data deriving from brain-resident monocytes, we discuss the impact of modulation of these epigenetic states and how they affect processes important for the development of a healthy brain, as well as mechanisms of neurodegenerative disease and aging. An understanding of the varied brain responses and pathologies in light of these novel gene regulatory systems in monocytes will lead to important new insights in the understanding of the aging process and the treatment and diagnosis of neurodegenerative disease.

  18. Mechanisms of modulation of brain microvascular endothelial cells function by thrombin.

    Science.gov (United States)

    Brailoiu, Eugen; Shipsky, Megan M; Yan, Guang; Abood, Mary E; Brailoiu, G Cristina

    2017-02-15

    Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca(2+) concentration in RBMVEC via Ca(2+) release from endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors and Ca(2+) influx from extracellular space. Thrombin increases nitric oxide production; the effect is abolished by inhibition of the nitric oxide synthase or by antagonism of PAR1 receptors. In addition, thrombin increases mitochondrial and cytosolic reactive oxygen species production via PAR1-dependent mechanisms. Immunocytochemistry studies indicate that thrombin increases F-actin stress fibers, and disrupts the tight junctions. Thrombin increased the RBMVEC permeability assessed by a fluorescent flux assay. Taken together, our results indicate multiple mechanisms by which thrombin modulates the function of RBMVEC and may contribute to the blood-brain barrier dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    Directory of Open Access Journals (Sweden)

    Justin A. Roby

    2014-01-01

    Full Text Available Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV, Japanese encephalitis virus (JEV, yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA derived from the 3' untranslated region (UTR. sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.

  20. Role of adipokines signaling in the modulation of T cells function

    Directory of Open Access Journals (Sweden)

    Claudio eProcaccini

    2013-10-01

    Full Text Available The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, termed adipokines, which can be considered as the bridge between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events leading to metabolic syndrome, inflammatory and/or autoimmune conditions. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, modulation of immune responses, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism, and so on. This report aims to discuss some of the recent topics of adipocytokine research and their related signaling pathways, that may be of particular importance as could lead to effective therapeutic strategies for obesity-associated diseases.

  1. The Macrophage Galactose-Type C-Type Lectin (MGL Modulates Regulatory T Cell Functions.

    Directory of Open Access Journals (Sweden)

    Ilaria Grazia Zizzari

    Full Text Available Regulatory T cells (Tregs are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the immunosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.

  2. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme.

    Directory of Open Access Journals (Sweden)

    Stephanie A Ragland

    2017-09-01

    Full Text Available Lysozyme is a cornerstone of innate immunity. The canonical mechanism for bacterial killing by lysozyme occurs through the hydrolysis of cell wall peptidoglycan (PG. Conventional type (c-type lysozymes are also highly cationic and can kill certain bacteria independently of PG hydrolytic activity. Reflecting the ongoing arms race between host and invading microorganisms, both gram-positive and gram-negative bacteria have evolved mechanisms to thwart killing by lysozyme. In addition to its direct antimicrobial role, more recent evidence has shown that lysozyme modulates the host immune response to infection. The degradation and lysis of bacteria by lysozyme enhance the release of bacterial products, including PG, that activate pattern recognition receptors in host cells. Yet paradoxically, lysozyme is important for the resolution of inflammation at mucosal sites. This review will highlight recent advances in our understanding of the diverse mechanisms that bacteria use to protect themselves against lysozyme, the intriguing immunomodulatory function of lysozyme, and the relationship between these features in the context of infection.

  3. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  4. RETRACTED: Adaptive neuro-fuzzy prediction of modulation transfer function of optical lens system

    Science.gov (United States)

    Petković, Dalibor; Shamshirband, Shahaboddin; Anuar, Nor Badrul; Md Nasir, Mohd Hairul Nizam; Pavlović, Nenad T.; Akib, Shatirah

    2014-07-01

    This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. Sections ;1. Introduction; and ;2. Modulation transfer function;, as well as Figures 1-3, plagiarize the article published by N. Gül and M. Efe in Turk J Elec Eng & Comp Sci 18 (2010) 71 (http://journals.tubitak.gov.tr/elektrik/issues/elk-10-18-1/elk-18-1-6-0811-9.pdf). Sections ;4. Adaptive neuro-fuzzy inference system; and ;6. Conclusion; duplicate parts of the articles previously published by the corresponding author et al in ;Expert Systems with Applications; 39 (2012) 13295-13304, http://dx.doi.org/10.1016/j.eswa.2012.05.072 and ;Expert Systems with Applications; 40 (2013) 281-286, http://dx.doi.org/10.1016/j.eswa.2012.07.076. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper is not under consideration for publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

  5. Structurally diverse MDM2-p53 antagonists act as modulators of MDR-1 function in neuroblastoma.

    Science.gov (United States)

    Chen, L; Zhao, Y; Halliday, G C; Berry, P; Rousseau, R F; Middleton, S A; Nichols, G L; Del Bello, F; Piergentili, A; Newell, D R; Lunec, J; Tweddle, D A

    2014-08-12

    A frequent mechanism of acquired multidrug resistance in human cancers is overexpression of ATP-binding cassette transporters such as the Multi-Drug Resistance Protein 1 (MDR-1). Nutlin-3, an MDM2-p53 antagonist, has previously been reported to be a competitive MDR-1 inhibitor. This study assessed whether the structurally diverse MDM2-p53 antagonists, MI-63, NDD0005, and RG7388 are also able to modulate MDR-1 function, particularly in p53 mutant neuroblastoma cells, using XTT-based cell viability assays, western blotting, and liquid chromatography-mass spectrometry analysis. Verapamil and the MDM2-p53 antagonists potentiated vincristine-mediated growth inhibition in a concentration-dependent manner when used in combination with high MDR-1-expressing p53 mutant neuroblastoma cell lines at concentrations that did not affect the viability of cells when given alone. Liquid chromatography-mass spectrometry analyses showed that verapamil, Nutlin-3, MI-63 and NDD0005, but not RG7388, led to increased intracellular levels of vincristine in high MDR-1-expressing cell lines. These results show that in addition to Nutlin-3, other structurally unrelated MDM2-p53 antagonists can also act as MDR-1 inhibitors and reverse MDR-1-mediated multidrug resistance in neuroblastoma cell lines in a p53-independent manner. These findings are important for future clinical trial design with MDM2-p53 antagonists when used in combination with agents that are MDR-1 substrates.

  6. Ghrelin modulates encoding-related brain function without enhancing memory formation in humans.

    Science.gov (United States)

    Kunath, N; Müller, N C J; Tonon, M; Konrad, B N; Pawlowski, M; Kopczak, A; Elbau, I; Uhr, M; Kühn, S; Repantis, D; Ohla, K; Müller, T D; Fernández, G; Tschöp, M; Czisch, M; Steiger, A; Dresler, M

    2016-11-15

    Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro

    Directory of Open Access Journals (Sweden)

    Laura P. Johnson

    2015-06-01

    Full Text Available Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs, which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation—another method used to modulate gut composition and function—could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre, inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

  8. Binary Pseudo-Random Gratings and Arrays for Calibration of Modulation Transfer Functions of Surface Profilometers

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Samuel K.; Anderson, Erik D.; Cambie, Rossana; McKinney, Wayne R.; Takacs, Peter Z.; Stover, John C.; Voronov, Dmitriy L.; Yashchuk, Valeriy V.

    2009-09-11

    A technique for precise measurement of the modulation transfer function (MTF), suitable for characterization of a broad class of surface profilometers, is investigated in detail. The technique suggested in [Proc. SPIE 7077-7, (2007), Opt. Eng. 47(7), 073602-1-5 (2008)]is based on use of binary pseudo-random (BPR) gratings and arrays as standard MTF test surfaces. Unlike most conventional test surfaces, BPR gratings and arrays possess white-noise-like inherent power spectral densities (PSD), allowing the direct determination of the one- and two-dimensional MTF, respectively, with a sensitivity uniform over the entire spatial frequency range of a profiler. In the cited work, a one dimensional realization of the suggested method based on use of BPR gratings has been demonstrated. Here, a high-confidence of the MTF calibration technique is demonstrated via cross comparison measurements of a number of two dimensional BPR arrays using two different interferometric microscopes and a scatterometer. We also present the results of application of the experimentally determined MTF correction to the measurement taken with the MicromapTM-570 interferometric microscope of the surface roughness of a super-polished test mirror. In this particular case, without accounting for the instrumental MTF, the surface rms roughness over half of the instrumental spatial frequency bandwidth would be underestimated by a factor of approximately 1.4.

  9. Effects of areca nut extracts on the functions of human neutrophils in vitro.

    Science.gov (United States)

    Hung, S L; Chen, Y L; Wan, H C; Liu, T Y; Chen, Y T; Ling, L J

    2000-08-01

    Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils. Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner. At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye. However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction. Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE. Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used. Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs. In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils. This effect may contribute to a less efficient elimination of bacteria from the periodontal environment. Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products.

  10. Simultaneously extracting multiple parameters via fitting one single autocorrelation function curve in diffuse correlation spectroscopy.

    Science.gov (United States)

    Dong, Lixin; He, Lian; Lin, Yu; Shang, Yu; Yu, Guoqiang

    2013-02-01

    Near-infrared diffuse correlation spectroscopy (DCS) has recently been employed for noninvasive acquisition of blood flow information in deep tissues. Based on the established correlation diffusion equation, the light intensity autocorrelation function detected by DCS is determined by a blood flow index αD(B), tissue absorption coefficient μ(a), reduced scattering coefficient μ'(s), and a coherence factor β. This study is designed to investigate the possibility of extracting multiple parameters such as μ(a), μ'(s), β, and αD(B) through fitting one single autocorrelation function curve and evaluate the performance of different fitting methods. For this purpose, computer simulations, tissue-like phantom experiments, and in vivo tissue measurements were utilized. The results suggest that it is impractical to simultaneously fit αD(B) and μ(a) or αD(B) and μ'(s) from one single autocorrelation function curve due to the large crosstalk between these paired parameters. However, simultaneously fitting β and αD(B) is feasible and generates more accurate estimation with smaller standard deviation compared to the conventional two-step fitting method (i.e., first calculating β and then fitting αD(B)). The outcomes from this study provide a crucial guidance for DCS data analysis.

  11. Limits on phonon information extracted from neutron pair-density functions

    Science.gov (United States)

    Graf, Matthias J.; Jeong, Il-Kyoung; Starr, Daniel L.; Heffner, R. H.

    2003-08-01

    We explore the possibility of extracting information about lattice dynamics in simple crystal structures from the neutron pair-density function (PDF) through inverse data analysis. Contrary to the claims by Dimitrov, Louca, and Röder [Phys. Rev. B 60, 6204 (1999)], and in agreement with recent work by Reichardt and Pintschovius [Phys. Rev. B 63, 174302 (2001)], we find that the PDF alone is not sufficient for constructing accurate phonon dispersions in the entire Brillouin zone in systems with complex lattice dynamics. However, our numerical simulations show that for monatomic fcc and bcc crystal structures it is, in principle, possible to obtain phonon moments of complex metals as well as phonon frequencies of simple metals within a few percent accuracy.

  12. Chemical composition and functional properties of starch extracted from the pejibaye fruit (Bactris gasepaes Kunth.

    Directory of Open Access Journals (Sweden)

    Biano Alves de Melo Neto

    2015-01-01

    Full Text Available This study aimed to establish the chemical composition and functional properties of the starch extracted